One intrinsic yet critical issue that troubles the field of fluorescence microscopy ever since its introduction is the unmatched resolution in the lateral and axial directions (i.e., resolution anisotropy), which severely deteriorates the quality, reconstruction, and analysis of 3D volume images. By leveraging the natural anisotropy, we present a deep self-learning method termed Self-Net that significantly improves the resolution of axial images by using the lateral images from the same raw dataset as rational targets. By incorporating unsupervised learning for realistic anisotropic degradation and supervised learning for high-fidelity isotropic recovery, our method can effectively suppress the hallucination with substantially enhanced image quality compared to previously reported methods. In the experiments, we show that Self-Net can reconstruct high-fidelity isotropic 3D images from organelle to tissue levels via raw images from various microscopy platforms, e.g., wide-field, laser-scanning, or super-resolution microscopy. For the first time, Self-Net enables isotropic whole-brain imaging at a voxel resolution of 0.2 × 0.2 × 0.2 μm3, which addresses the last-mile problem of data quality in single-neuron morphology visualization and reconstruction with minimal effort and cost. Overall, Self-Net is a promising approach to overcoming the inherent resolution anisotropy for all classes of 3D fluorescence microscopy.

Iodine deficiency during pregnancy is a widespread public health concern, but indicators and methods for assessing iodine nutritional status are lacking. Serum iodine concentration (SIC) is an important iodine metabolism biomarker and can, to some extent, predict the risk of thyroid diseases, making it a potential biomarker for assessing individual iodine nutrition levels. Our study aimed to analyze the relationship between SIC and thyroid function in a cohort of mild iodine deficient pregnant women in China in order to explore the potential of SIC as a biomarker of individual iodine status in pregnancy. A total of 1540 early pregnant women (gestation < 10 weeks) aged 18 to 45 years old were included in the final study from a Zhejiang multicenter population-based mother and child cohort. Repeated measures of SIC, urinary iodine concentration (UIC), and thyroid function were taken at approximately 10, 17, and 32 weeks of gestation. The SIC was statistically correlated with all thyroid function indexes in the first trimester, and a very strong positive correlation with FT4 over three trimesters (r = 0.449, 0.550, and 0.544, respectively). Pregnant women with an SIC < 72.4 µg/L were at a higher risk of hypothyroxinemia (adjusted OR = 8.911, 95% CI = 5.141-15.447) and iodine deficiency (adjusted OR = 1.244, 95% CI = 1.031-1.502), while those with an SIC > 93.9 µg/L were at a higher risk of thyrotoxicosis (adjusted OR = 11.064, 95% CI = 6.324-19.357) and excessive iodine (adjusted OR = 11.064, 95% CI = 6.324-19.357). In contrast, the UIC was not correlated with thyroid diseases (p > 0.05). These findings indicate that the SIC is a potential biomarker for assessing individual iodine nutrition and thyroid dysfunction in pregnant women.

The systematic comparison of cancer survival between China and the USA is rare. Here we aimed to assess the magnitude of survival disparities and disentangle the impact of the stage at diagnosis between a Chinese metropolitan city and the USA on cancer survival.

SOX9 plays a crucial role in the male reproductive system, brain, and kidneys. In this study, we firstly analyzed the complete cDNA sequence and expression patterns for SOX9 from Gekko japonicus SOX9 (gjSOX9), carried out bioinformatic analyses of physiochemical properties, structure, and phylogenetic evolution, and compared these with other members of the gjSOX family. The results indicate that gjSOX9 cDNA comprises 1895 bp with a 1482 bp ORF encoding 494aa. gjSOX9 was not only expressed in various adult tissues but also exhibited a special spatiotemporal expression pattern in gonad tissues. gjSOX9 was predicted to be a hydrophilic nucleoprotein with a characteristic HMG-Box harboring a newly identified unique sequence, "YKYQPRRR", only present in SOXE members. Among the 20 SOX9 orthologs, gjSOX9 shares the closest genetic relationships with Eublepharis macularius SOX9, Sphacrodactylus townsendi SOX9, and Hemicordylus capensis SOX9. gjSOX9 and gjSOX10 possessed identical physicochemical properties and subcellular locations and were tightly clustered with gjSOX8 in the SOXE group. Sixteen gjSOX family members were divided into six groups: SOXB, C, D, E, F, and H with gjSOX8, 9, and 10 in SOXE among 150 SOX homologs. Collectively, the available data in this study not only facilitate a deep exploration of the functions and molecular regulation mechanisms of the gjSOX9 and gjSOX families in G. japonicus but also contribute to basic research regarding the origin and evolution of SOX9 homologs or even sex-determination mode in reptiles.

Cancer stem cells (CSCs) have been proposed to explain tumor relapse and chemoresistance in various types of cancers, and androgen receptor (AR) has been emerged as a potential regulator of stemness in cancers. However, the underlying mechanism of AR-regulated CSCs properties and chemoresistance in gastric cancer (GC) remains unknown. Here, we shown that AR is upregulated in GC tissues and correlates with poor survival rate and CSCs phenotypes of GC patients. According to our experimental data, overexpression of AR upregulated the expression of CSCs markers and this was consistent with the result concluded from data analysis that the expression of AR was positively correlated with CD44 in GC patients. In addition, AR overexpression obviously enhanced the tumor sphere formation ability and chemoresistance of GC cells in vitro. Whereas these effects were attenuated by inhibition of AR. These results were further validated in vivo that MGC-803 cells overexpressing AR had stronger properties to initiate gastric tumorigenesis than the control cells, and inhibition of AR increased the chemosensitivity of GC cells. Mechanically, AR upregulated CD44 expression by directly binding to its promoter region and Yes-associated protein 1 (YAP1) served as the co-factor of AR, which was demonstrated by the fact that the promoting effects of AR on GC cells stemness were partially counteracted by YAP1 knockdown. Thus, this study revealed that AR facilitates CSCs properties and chemoresistance of GC cells via forming complex with YAP1and indicates a potential therapeutic approach to GC patients.

Dietary modulation of the gut microbiota has recently received considerable attention. It is well established that consumption of berries confers a number of health benefits. We previously reported that a black raspberry (BRB)-rich diet effectively modulates the gut microbiota. Given the role of anthocyanins in the health benefits of berries, coupled with interactions of gut microbial metabolites with host health, the objective of this follow-up study was to further characterize the profile of functional metabolites in the gut microbiome modulated by anthocyanins. We utilized a berry-derived classic anthocyanin, cyanidin-3-glucoside (C3G), combined with a mouse model to probe C3G-associated functional metabolic products of gut bacteria through a mass spectrometry-based metabolomic profiling technique. Results showed that C3G substantially changed the gut microbiota of mice, including its composition and metabolic profile. A distinct metabolic profile in addition to a variety of key microbiota-related metabolites was observed in C3G-treated mice. Microbial metabolites involved in protein digestion and absorption were differently abundant between C3G-treated and control mice, which may be linked to the effects of berry consumption. Results of the present study suggest the involvement of the gut microbiota in the health benefits of C3G, providing evidence connecting the gut microbiota with berry consumption and its beneficial effects.

Surgical correction for recurrent patellar dislocation (RPD) can improve femoral trochlear morphology; nonetheless, the effects of surgical correction on femoral condyle morphology are unclear.

Circumcision is a common pediatric operation, and distraction technique can be used as an adjunct analgesic method during the perioperative period. The study aims to explore the effect of distraction techniques on reducing pain, fear, and anxiety in children undergoing circumcision. The PubMed, ClinicalTrials.gov, and Embase databases were searched for articles published from January 1, 2000, to December 31, 2023. Only randomized controlled trials (RCTs) were included. Meta-analysis and forest plots were carried out using Review Manager 5.4.1 software, and outcomes were reviewed by two authors independently. We used the Risk of Bias assessment form (ROB2) developed by the Cochrane Collaboration to assess the quality of included studies. PRISMA 2020 guidelines were used in this article to achieve the quantitative and qualitative synthesis of data. A total of seven RCTs were included. The intervention group consisted of 417 patients, while the control group had 245 patients. The meta-analysis and sensitivity analysis results showed that the distraction technique could significantly relieve pain (MD -1.3, 95% confidence interval [CI]: [-1.61 to -0.99], p < .00001), fear (SMD -1.04, 95%CI -1.68 to -0.4, p = .001), and anxiety (SMD -1.07, 95%CI [-1.64 to -0.51], p = .0002). Similarly, therapeutic play significant could significantly relieve fear (MD -0.4, 95%CI [-0.71 to -0.1], p = .01) and anxiety (SMD -1.31, 95%CI [-2.59 to -0.04], p = .04), virtual reality (VR) could significantly relieve anxiety (SMD -0.67, 95%CI [-0.98 to -0.37], p < .0001). Distraction techniques can alleviate perioperative pain, fear, and anxiety in children undergoing circumcision.

Lysine crotonylation (Kcr) is a crucial protein post-translational modification found in histone and non-histone proteins. It plays a pivotal role in regulating diverse biological processes in both animals and plants, including gene transcription and replication, cell metabolism and differentiation, as well as photosynthesis. Despite the significance of Kcr, detection of Kcr sites through biological experiments is often time-consuming, expensive, and only a fraction of crotonylated peptides can be identified. This reality highlights the need for efficient and rapid prediction of Kcr sites through computational methods. Currently, several machine learning models exist for predicting Kcr sites in humans, yet models tailored for plants are rare. Furthermore, no downloadable Kcr site predictors or datasets have been developed specifically for plants. To address this gap, it is imperative to integrate existing Kcr sites detected in plant experiments and establish a dedicated computational model for plants.

In 2015, we measured polycyclic aromatic hydrocarbons (PAHs) in atmospheric fine particulate matter (PM2.5) collected from 5 cities in Zhejiang Province. The mean toxic equivalent quotient (TEQ) values of benzo(a)pyrene (BaP) ranged between 1.2-3.1 ng/m3. The BaP-TEQ displayed seasonal trends, such that winter > spring and autumn > summer. During the winter, the most abundant individual PAHs were 4-6ring PAHs (84.04-91.65%). The median daily intake of atmospheric PAHs ranged between 2.0-7.4 ng/day for all populations, with seasonal trends identical to that of BaP-TEQ. The 95th incremental lifetime cancer risk (ILCR) values induced by PM2.5-bound PAHs were far lower than 10-6 for all populations. The data suggested that the pollution levels in the 5 Zhejiang Province cities were higher than the Chinese National Ambient Air Quality Standard (NAAQS). In the future, relevant measures should be taken to control atmospheric PAHs, especially 4-6 ring PAHs. The data also revealed no obvious cancer risk for populations residing in these 5 cities of Zhejiang Province.

Decorin is a multifunctional molecule of the extracellular matrix and impedes different kinds of tumor cell growth, but the role and molecular mechanism by which decorin inhibits HepG2 cells is not fully understood. Our objective was to construct recombinant human decorin (pcDNA3.1-DCN) and to explore the mechanism by which it inhibits HepG2 cells.

Progesterone is essential for the proliferation and differentiation of mammary gland epithelium. Studies of breast cancer cells have demonstrated a biphasic progesterone response consisting of an initial proliferative burst followed by sustained growth arrest. However, the transcriptional factors acting with the progesterone receptor (PR) to mediate the effects of progesterone on mammary cell growth and differentiation remain to be determined. Recently, it was demonstrated that signal transducer and activator of transcription 6 (Stat6) is a cell growth suppressor. Similar to progesterone-bound PR, Stat6 acts by inducing the expression of the G1 cyclin-dependent kinase inhibitors p21 and p27. The possible interaction between Stat6 and progesterone pathways in mammary cells was therefore investigated in the present study.

Post-transcriptional gene silencing is commonly observed in polyploid species and often poses a major limitation to plant improvement via biotechnology. Five plant viral suppressors of RNA silencing were evaluated for their ability to counteract gene silencing and enhance the expression of the Enhanced Yellow Fluorescent Protein (EYFP) or the β-glucuronidase (GUS) reporter gene in sugarcane, a major sugar and biomass producing polyploid. Functionality of these suppressors was first verified in Nicotiana benthamiana and onion epidermal cells, and later tested by transient expression in sugarcane young leaf segments and protoplasts. In young leaf segments co-expressing a suppressor, EYFP reached its maximum expression at 48-96 h post-DNA introduction and maintained its peak expression for a longer time compared with that in the absence of a suppressor. Among the five suppressors, Tomato bushy stunt virus-encoded P19 and Barley stripe mosaic virus-encoded γb were the most efficient. Co-expression with P19 and γb enhanced EYFP expression 4.6-fold and 3.6-fold in young leaf segments, and GUS activity 2.3-fold and 2.4-fold in protoplasts compared with those in the absence of a suppressor, respectively. In transgenic sugarcane, co-expression of GUS and P19 suppressor showed the highest accumulation of GUS levels with an average of 2.7-fold more than when GUS was expressed alone, with no detrimental phenotypic effects. The two established transient expression assays, based on young leaf segments and protoplasts, and confirmed by stable transgene expression, offer a rapid versatile system to verify the efficiency of RNA silencing suppressors that proved to be valuable in enhancing and stabilizing transgene expression in sugarcane.

microRNAs are small noncoding RNAs that modulate a variety of cellular processes by regulating multiple targets, which can promote or inhibit the development of malignant behaviors. Accumulating evidence suggests miR-24 plays important roles in human carcinogenesis. However, its precise biological role remains largely elusive. This study examined the role of miR-24 in gastric cancer (GC).

Scutellarin (SC), mainly extracted from the Chinese herb Erigeron breviscapus (vant.), has been reported to possess various pharmacological activities; however, its effects on Alzheimer's disease (AD) have not been systemically reported. The protective effects of SC on AD were investigated using an L‑glutamic acid (L‑Glu)‑damaged HT22 cell apoptosis model and an aluminum chloride plus D‑galactose‑induced AD mouse model. In L‑Glu‑damaged HT22 cells, SC significantly increased cell viability, inhibited lactate dehydrogenase release, reduced caspase‑3 activity and suppressed apoptosis, which were determined via an MTT assay, an in vitro Toxicology Assay kit, a Caspase‑3 activity assay kit, and propidium iodide and Annexin V staining. Furthermore, SC suppressed the accumulation of intracellular reactive oxygen species (ROS), restored the dissipation of mitochondrial membrane potential, enhanced the expression of antiapoptotic proteins and reduced the expression of pro‑apoptotic proteins, as determined by immunofluorescence assays and western blotting. In AD mice, SC enhanced vertical and horizontal movements in an autonomic activity test, and reduced the escape latency time in the water maze test. SC reduced the deposition of amyloid β1‑42 (Aβ1‑42) and the expression of phosphorylated‑Tau in the hippocampus as determined by immunohistochemistry analysis, but enhanced the serum levels of Aβ1‑42 of AD mice as determined by ELISA. ELISA analyses also revealed that SC enhanced the levels of acetylcholine, and superoxide dismutase in serum and brain lysate, whereas reduced the levels of ROS in brain lysate of AD mice. The present study confirmed that the protective effects of SC in AD in vitro and in vivo are associated with its antioxidant and antiapoptotic properties.

Elevated serum urate, which is regulated at multiple levels including genetic variants, is a risk factor for gout and other metabolic diseases. This study aimed to investigate the association between UCP2 variants and serum urate as well as hyperuricemia in a Chinese population. In total, 4332 individuals were genotyped for two common UCP2 variants, -866G/A and Ala55Val. These loci were not associated either serum urate level or with a risk of hyperuricemia in the total group of subjects. However, in females, -866G/A and Ala55Val were associated with a lower serum urate (P = 0.006 and 0.014, seperately) and played a protective role against hyperuricemia (OR = 0.80, P = 0.018; OR = 0.79, P = 0.016). These associations were not observed in the males. After further stratification, the two loci were associated with serum urate in overweight, but not underweight females. The haplotype A-T (-866G/A-Ala55Val) was a protective factor for hyperuricemia in the female subgroup (OR = 0.80, P = 0.017). This present study identified a novel gene, UCP2, that influences the serum urate concentration and the risk of hyperuricemia, and the degree of association varies with gender and BMI levels.

Gastric cancer (GC) is one of the most common tumors worldwide and involves extensive local tumor invasion, metastasis, and poor prognosis. Understanding mechanisms regulating progression of GC is necessary for developing effective therapeutic strategies. Tissue transglutaminase-2 (TG2), a multifunctional member of the transglutaminase family, has been shown to be critical for tumor initiation and progression. However, how TG2 promotes the progression of GC is unknown. We report that TG2 was highly expressed in GC tissues and positively associated with depth of tumor invasion and late TNM stage. With gain- and loss-of-function approaches, we observed that TG2 promoted GC cell proliferation, migration, invasion, as well as tumorigenesis and peritoneal metastasis in vivo. These events were associated with the ERK1/2 pathway activation and an ERK1/2 inhibitor (U0126) inhibited cell proliferation, migration, and invasion induced by overexpression of TG2. In summary, TG2 contributes to tumorigenesis and progression of GC by activating the ERK1/2 signaling pathway and is a potential therapeutic target of metastatic gastric cancer.

Transcriptome-wide maps of RNA binding protein (RBP)-RNA interactions by immunoprecipitation (IP)-based methods such as RNA IP (RIP) and crosslinking and IP (CLIP) are key starting points for evaluating the molecular roles of the thousands of human RBPs. A significant bottleneck to the application of these methods in diverse cell lines, tissues, and developmental stages is the availability of validated IP-quality antibodies. Using IP followed by immunoblot assays, we have developed a validated repository of 438 commercially available antibodies that interrogate 365 unique RBPs. In parallel, 362 short-hairpin RNA (shRNA) constructs against 276 unique RBPs were also used to confirm specificity of these antibodies. These antibodies can characterize subcellular RBP localization. With the burgeoning interest in the roles of RBPs in cancer, neurobiology, and development, these resources are invaluable to the broad scientific community. Detailed information about these resources is publicly available at the ENCODE portal (https://www.encodeproject.org/).

Being the major reason of recurrence and death after surgery, peritoneal metastasis of gastric cancer dooms the prognosis of advanced gastric cancer patients. Regenerating islet-derived family, member 4 (REG4) is believed to promote peritoneal metastasis, however, its mechanism is still a moot point at present. In the present study, we show that high expression of REG4 correlates with advanced stage and poor survival prognosis for gastric cancer patients. REG4 overexpression significantly enhances peritoneal metastasis by increasing adhesion ability. Moreover, SP1 is proved to be a transcription factor of REG4 and induce REG4 expression upon TGF-alpha stimulation. Also, G protein-coupled receptor 37 (GPR37) is identified to be in the same complex of REG4, which mediates REG4's signal transduction and promotes peritoneal metastasis of gastric cancer cell. Interestingly, we also discover a positive feedback loop triggered by REG4, amplifying itself through EGFR transactivation, consisting of GPR37, ADAM17, TGF-alpha, EGFR, SP1 and REG4. In conclusion, REG4 promotes peritoneal metastasis of gastric cancer through GPR37 and triggers a positive feedback loop.

Pancreatic neuroendocrine tumor (pNET) is a clinically rare and heterogeneous group of tumors; its pharmacogenetic characteristics are not fully understood. This study was designed to examine the relationship between key gene variations and disease development and prognosis among Chinese patients with pNET.