Abnormal brain network connectivity is strongly implicated in the pathogenesis of schizophrenia. The striatum, consisting of the caudate and putamen, is the major treatment target for antipsychotics, the primary treatments for schizophrenia; however, there are few studies on the functional connectivity (FC) of striatum in drug-naive early-onset schizophrenia (EOS) patients. We examined the FC values of the caudate nucleus and putamen with whole brain by resting-state functional magnetic resonance imaging (RS-fMRI) and the associations with indices of clinical severity. Patients demonstrated abnormal FC between subregions of the putamen and both the visual network (left middle occipital gyrus) and default mode network (bilateral anterior cingulate, left superior frontal, and right middle frontal gyri). Furthermore, FC between dorsorostral putamen and left superior frontal gyrus correlated with both positive symptom subscore and total score on the Positive and Negative Syndrome Scale (PANSS). These findings demonstrate abnormal FC between the striatum and other brain areas even in the early stages of schizophrenia, supporting neurodevelopmental disruption in disease etiology and expression.

Five previously undescribed epoxy octa-hydronaphthalene polyketides, altereporenes A-E (1-5) were isolated from rice culture of the endophytic fungus Alternaria sp. YUD20002 derived from the tubers of Solanum tuberosum. Their structures were determined on the basis of comprehensive spectroscopic analyses, while the absolute configurations were elucidated by the comparison of experimental and calculated specific rotations. Meanwhile, the antimicrobial, cytotoxic, anti-inflammatory and acetylcholinesterase inhibitory activities of compounds 1-5 were also investigated.

The medical damage litigations after knee arthroplasty are on the rise year by year. However, few studies examined the litigation after knee arthroplasty. This study analyzed the litigation of medical damage after knee replacement in the past ten years based on a Chinese database. It synthesized the focus of the dispute in these cases to provide a reference for doctors to reduce the risk of litigation.

Fermented foods often have attractive flavor characteristics to meet various human demands. An ever-challenging target is the production of fermented foods with equal flavor profiles outside the product's origin. However, the formation of geography-dependent flavor in high-complexity fermentations remains poorly understood. Here, taking Chinese liquor (baijiu) fermentation as an example, we collected 403 samples from 9 different locations in China across a latitude range of 27°N to 37°N. We revealed and validated the geography-dependent flavor formation patterns by using culture-independent (metabolomics, metagenomics, and metatranscriptomics) and culture-dependent tools. We found that the baijiu microbiomes along with their metabolites were flavor related and geography dependent. The geographical characteristics were determined mainly by 20 to 40 differentiated chemical markers in metabolites and the latitude-dependent fungal structure of the microbiome. About 48 to 156 core microbiota members out of 735 bacterial genera and 290 fungal genera contributed to the chemical markers. The contributions of both fungi and bacteria were greater than those from either bacteria or fungi alone. Representatively, we revealed that dynamic interdependent interactions between yeasts and Lactobacillus facilitated the metabolism of heterocyclic flavor chemicals such as 2-acetylpyrrole, 2,3,5-trimethylpyrazine, and 2-acetylfuran. Moreover, we found that the intraspecific genomic diversity and microbial structure were two biotic factors that contributed to dynamic microbiome assembly. Based on the assembly pattern, adjusting the composition and distribution of initial species was one option to regulate the formation of diverse flavor characteristics. Our study provided a rationale for developing a microbiome design to achieve a defined flavor goal. IMPORTANCE People consume many spontaneously fermented foods and beverages with different flavors on a daily basis. One crucial and hotly discussed question is how to reproduce fermented food flavor without geographical limitations to meet diverse human demands. The constantly enriched knowledge of the microbial contribution to fermented flavor offers valuable insights into flavor biotechnological development. However, we still have a poor understanding of what factors limit the reproduction of fermented flavor outside the product's origin in high-complexity spontaneous fermentations. Here, taking baijiu fermentation as an example, we revealed that geography-dependent flavor was contributed mainly by fungus-bacterium cooperative metabolism. The distinct initial microbial composition, distribution, and intraspecific genomic diversity limited reproducible microbial interactions and metabolism in different geographical areas. The abundant microbial resources and predicted fungus-bacterium interactions found in baijiu fermentation enable us to design a synthetic microbial community to reproduce desired flavor profiles in the future.

Low temperature plasma (LTP) is a promising cancer therapy in clinical practice. In this study, dielectric barrier discharge plasma with helium gas was used to generate LTP. Significant increases in extracellular and intracellular reactive species were found in lung cancer cells (CALU-1 and SPC-A1) after LTP treatments. Cells viability and apoptosis assays demonstrated that LTP inhibited cells viability and induced cells death, respectively. Moreover, Western blotting revealed that the growth of CALU-1 cells was suppressed by LTP via the VEGF/VEGFR2/RAS/ERK axis for the first time. The results showed that LTP-induced ROS and RNS could inhibit the growth of lung cancer cells via VEGF/VEGFR2/RAS/ERK axis. These findings advance our understanding of the inhibitory mechanism of LTP on lung cancer and will facilitate its clinical application.

The processes of cancer initiation, progression, and response to therapy are affected by the sex of cancer patients. Immunotherapy responses largely depend on the tumor microenvironment (TME), but how sex may shape some TME features, remains unknown. Here, we analyzed immune infiltration signatures across 19 cancer types from 1771 male and 1137 female patients in The Cancer Genome Atlas to evaluate how sex may affect the tumor mutational burden (TMB), immune scores, stromal scores, tumor purity, immune cells, immune checkpoint genes, and functional pathways in the TME. Pan-cancer analyses showed higher TMB and tumor purity scores, as well as lower immune and stromal scores in male patients as compared to female patients. Lung adenocarcinoma, lung squamous carcinoma, kidney papillary carcinoma, and head and neck squamous carcinoma showed the most significant sex biases in terms of infiltrating immune cells, immune checkpoint gene expression, and functional pathways. We further focused on lung adenocarcinoma samples in order to identify and validate sex-specific immune cell biomarkers with prognostic potential. Overall, sex may affect the tumor microenvironment, and sex-specific TME biomarkers may help tailor cancer immunotherapy in certain cancer types.

Electro-peroxone (EP) is an emerging advanced oxidation process which combines electro-generation H2O2 and ozone for removing organic contaminants. In this paper, a platinum plate as anode, a method of electrochemical oxidation is adopted to modify graphite felt (GF) cathode to promote H2O2 yield and TOC removal from oxalic acid solution in EP process, its performance, mechanism and stability were discussed. Compared with original GF cathode, 2.6 times H2O2 yield can be achieved by the 5 min electrochemically modified GF (GF-5). The high electrochemical activity of the modified GF can be ascribed to introducing numerous surface oxygen-containing functional groups (OGs), which not only decreased the impedance, but also increased the amount of active site of O2 reduction. The production of H2O2 with GF-5 cathode improved with the increased initial pH, cathodic potential and O2 flow rate, while this promoting effect was not observed in GF cathode. Compared with GF cathode, TOC removal rate was improved by 21.5% with GF-5 cathode due to higher H2O2 yield in EP process. The primary pathway of TOC removal is electrochemically-driven peroxone process, and hydroxyl radical (·OH) is the dominant reactive species. Furthermore, GF-5 cathode had a good stability due to the protection of H2O2 and free electrons injected. The results indicate that the electrochemically modified GF severed as the cathode of EP processes has significant efficiency and stability in the removal of ozone-refractory organic contaminants.

Niemann-Pick disease type C1 (NPC1) is a neurodegenerative disorder characterized by lysosomal storage of free cholesterol. 2-Hydroxypropyl-β-cyclodextrin (HPβCD) is a cyclic oligosaccharide derivative that is being developed to treat NPC1. Recently, metformin was reported to be beneficial in various neurodegenerative diseases, such as Alzheimer's and Huntington's diseases. In this study, we examined the effects of combined treatment with HPβCD and metformin on Npc1 -/- mice. Unfortunately, body weight and survival rates showed that cotreatment with metformin did not extend survival time and increase the body weight of HPβCD-treated Npc1 -/- mice. However, cotreatment with metformin reduced inflammatory response and inhibited the proinflammatory cytokine release in the brain, liver and spleen of HPβCD-treated Npc1 -/- mice. Furthermore, metformin did not reduce the free cholesterol levels in Npc1 -/- brain tissue or fibroblasts. In conclusion, our results demonstrate that metformin does not show beneficial effects on body weight or survival time but reduced the inflammatory response in a mouse model of NPC1 when combined with HPβCD.

To investigate the effect of eupatilin in asthma treatment, we evaluated its therapeutic effect and related signal transduction in OVA-induced asthmatic mice and LPS-stimulated RAW264.7 cells. The BALF was tested for changes in lung inflammatory cells. Th2 cytokines in the BALF and OVA-IgE in the serum were measured by ELISA. H&E and PAS staining were used to evaluate histopathological changes in mouse lungs. The key proteins NF-κB, MAPK, and Nrf2 in lung tissues were quantitatively analyzed by Western blotting. Finally, we evaluated the effect of eupatilin on cytokines and related protein expression in LPS-stimulated RAW 264.7 cells in vitro. In OVA-induced asthmatic mice, eupatilin reduced the numbers of inflammatory cells, especially neutrophils and eosinophils. Eupatilin also decreased the levels of IL-5, IL-13 in the BALF and OVA-IgE in the serum. Furthermore, eupatilin inhibited the activation of NF-κB and MAPK pathways and increased the expression of Nrf2 in OVA-induced asthmatic mice. In vitro, eupatilin significantly reduced LPS-stimulated NO, IL-6, and ROS production. Additionally, the NF-κB, MAPK, and Nrf2 protein expression in LPS-stimulated RAW264.7 cells was consistent with that in OVA-induced asthmatic lung tissues. In summary, eupatilin attenuated OVA-induced asthma by regulating NF-κB, MAPK, and Nrf2 signaling pathways. These results suggest the utility of eupatilin as an anti-inflammatory drug for asthma treatment.

Porcine reproductive and respiratory syndrome (PRRS), caused by PRRSV, has ranked among the most economically important veterinary infectious diseases globally. Recently, tripartite motif (TRIMs) family members have arisen as novel restriction factors in antiviral immunity. Noteworthy, TRIM26 was reported as a binding partner of IRF3, TBK1, TAB1, and NEMO, yet its role in virus infection remains controversial. Herein, we showed that TRIM26 bound N protein by the C-terminal PRY/SPRY domain. Moreover, ectopic expression of TRIM26 impaired PRRSV replication and induced degradation of N protein. The anti-PRRSV activity was independent of the nuclear localization signal (NLS). Instead, deletion of the RING domain, or the PRY/SPRY portion, abrogated the antiviral function. Finally, siRNA depletion of TRIM26 resulted in enhanced production of viral RNA and virus yield in porcine alveolar macrophages (PAMs) after PRRSV infection. Overexpression of an RNAi-resistant TRIM26 rescue-plasmid led to the acquisition of PRRSV restriction in TRIM26-knockdown cells. Together, these data add TRIM26 as a potential target for drug design against PRRSV.

Perioperative chemotherapy (PEC) and neoadjuvant chemotherapy (NAC) have become a vital part of locally advanced gastric cancer (LAGC) treatment, but the optimal duration of PEC has not been studied. The aim of this study was to demonstrate the possibility of duration reduction in PEC in the adjuvant chemotherapy (AC) phase for ypN0 patients.

Preeclampsia (PE) is a major cause of maternal and perinatal morbidity and mortality. Studies on the role of microRNAs (miRNAs), in the pathogenesis of PE through their effects on trophoblast function have been reported, but roles for some miRNAs including miR-513c-5p, have not been identified. We aimed to evaluate potential miRNA candidates that regulate the LRP6 mRNAand to elucidate the possible mechanism in PE. Potential miRNAs were selected by bioinformatics analysis, PCR of placenta tissues and dual luciferase reporter assay of HTR-8/SVneo cells.

Platinum (Pt) derivatives such as cisplatin and carboplatin are the class of drugs with proven activity against triple-negative breast cancer (TNBC). This is due to the ability of Pt compounds to interfere with the DNA repair mechanisms of the neoplastic cells. Taxanes have been efficacious against estrogen receptor-negative tumors and act by disruption of microtubule function. Due to their distinct mechanisms of action and routes of metabolism, the combination of the Pt agents and taxanes results in reduced systemic toxicity, which is ideal for treating TNBC. Also, the sensitivity of BRCA1-mutated cells to taxanes remains unsolved as in vitro evidence indicates resistance against taxanes due to BRCA1 mutations. Recent evidence suggests that the combination of carboplatin and paclitaxel resulted in better pathological complete response (pCR) in patients with TNBC, both in neoadjuvant and adjuvant settings. In vitro studies showed sequential dependency and optimal time scheduling of Pt- and taxane-based chemotherapy. Also, combining carboplatin with docetaxel in the NAC regimen yields an excellent pCR in patients with BRCA-associated and wild-type TNBC. TNBC is a therapeutic challenge that can be tackled by identifying new therapeutic sub-targets and specific cross-sections that can be benefitted from the addition of Pt- and taxane-based chemotherapy. This review summarizes the merits as well as the mechanism of Pt- and taxane-based adjuvant and neoadjuvant chemotherapies in early TNBC from the available and ongoing clinical studies.

The fiber yield and quality of cotton are greatly and periodically affected by water deficit. However, the molecular mechanism of the water deficit response in cotton fiber cells has not been fully elucidated.

To investigate if a traditional Chinese medicine formulation, called "Yiqihuoxue" (YQHX), could improve diabetic atherosclerosis (DA) and explore potential mechanisms based on DNA methylation.

Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is one of the four subtypes of gastric carcinoma and its unique clinicopathological mechanism is unclear. Herein, the expression of endothelin-1 (ET-1) in EBVaGC was lower than of Epstein-Barr virus-negative gastric carcinoma (EBVnGC) and associated with a low frequency of lymph node metastasis of EBVaGC. Functional studies showed that the activation of ET-1/endothelin receptor type A (ETAR) axis could promote cell growth, migration, and antiapoptosis. The expression of the ET-1 gene was unrelated to methylation of its promoter region and miRNAs (-1, -125a, -125b). After being treated with MEK1/2 inhibitor (PD0325901), the inactivation of ERK1/2 pathway resulted in downregulation of ET-1 and forkhead box O1 (FOXO1) expression. Further, FOXO1 knockdown decreased the ET-1 expression. These findings indicated that ET-1 could be involved in development of gastric cancer and EBV could suppress the expression of ET-1 via the regulation of the transcription factor FOXO1 through the MAPK/ERK pathway. IMPORTANCE The relationship between Epstein-Barr virus and gastric cancer has been relatively clear. However, there are still many unresolved mechanisms of the virus in tumorigenesis. In recent years, activation of the endothelin-1 signaling axis has been found to play an important role in tumorigenesis, which is involved in tumor angiogenesis and epithelial-mesenchymal transition. EBV genes. In our study, we found that ET-1 was low-expressed in EBV-positive gastric cancer cells, which was due to the inhibition of ERK signaling by EBNA1 through the repression of FOXO1 expression. The low expression of ET-1 limits the proliferation, migration, and anti-apoptotic ability of tumor cells. These findings contribute to further understanding of the role of EBV in EBV-associated gastric cancer.

Preoperative carbohydrates (CHO) supplement has been widely investigated in nondiabetic patients undergoing a variety of surgeries. It has been proved that preoperative CHO could alleviate postoperative insulin resistance (IR) and improve patients' well-being in nondiabetic patients. However, it remains controversial whether preoperative CHO could yield similar effects in diabetic patients. Till now, seldom has the administration of preoperative CHO been investigated in diabetic patients and there are limited studies reporting IR and postoperative recovery of diabetic patients undergoing cardiac surgery.

The lepidopteran crop pest Plutella xylostella causes severe constraints on Brassica cultivation. Here, we report a novel role for RPX1 (resistance to P. xylostella) in resistance to this pest in Arabidopsis thaliana. The rpx1-1 mutant repels P. xylostella larvae, and feeding on the rpx1-1 mutant severely damages the peritrophic matrix structure in the midgut of the larvae, thereby negatively affecting larval growth and pupation. This resistance results from the accumulation of defence compounds, including the homoterpene (3E)-4,8-dimethyl-1,3,7-nonatriene (DMNT), due to the upregulation of PENTACYCLIC TRITERPENE SYNTHASE 1 (PEN1), which encodes a key DMNT biosynthetic enzyme. P. xylostella infestation and wounding induce RPX1 protein degradation, which may confer a rapid response to insect infestation. RPX1 inactivation and PEN1 overexpression are not associated with negative trade-offs for plant growth but have much higher seed production than the wild-type in the presence of P. xylostella infestation. This study offers a new strategy for plant molecular breeding against P. xylostella.

Knee osteoarthritis (OA) is a prevalent disabling disorder that involves changes in articular cartilage damage, subchondral bone remodeling, synovitis, and abnormal infrapatellar fat pad (IPFP). Due to the complicated etiology and numerous phenotypes of knee OA, limited improvement is achieved for treatments among knee OA patients with different phenotypes. Inflammatory OA phenotype is a typical knee OA phenotype, and individualized treatment targeting inflammation is a promising way to obtain an optimal therapeutic effect for people with inflammatory knee OA phenotype. Glucocorticoid is a traditional anti-inflammatory drug for knee OA, and intra-articular glucocorticoid injections are recommended clinically. However, emerging evidence has shown that repeated intra-articular glucocorticoid injections in the long term would induce cartilage loss. IPFP and its adjacent synovium are considered as the main source of inflammation in knee OA. This GLITTERS trial aims to investigate if a glucocorticoid injection into the IPFP is effective and safe over 12 weeks among knee OA patients with an inflammatory phenotype.

To investigate the effects of different anesthetic methods on postoperative immune function in patients undergoing gastrointestinal tumor resection. Ninety patients undergoing laparoscopic gastrointestinal tumor resection were divided into 3 groups. Patients in the GA group were anesthetized by total intravenous anesthesia. The GE group was anesthetized by general anesthesia combined with epidural anesthesia. The GN group was anesthetized by general anesthesia combined with bilateral Transversus Abdominis Plane block (TAP) and rectus sheath nerve blocks. General anesthesia is total intravenous anesthesia in all three groups. Blood samples were taken to test the changes of peripheral lymphocyte subtype analysis, and levels of plasma cortisol, epinephrine, norepinephrine. Also, the dosage of anesthetic drugs, recovery time, and visual analog scale (VAS) scores were recorded. Postoperative immune indexes, including CD4 count, CD8 count, B, and NK cells, in the GE group were significantly higher than those in NA and GA groups (P < 0.01). Perioperative stress indices, including epinephrine levels, norepinephrine level and aldosterone level, in the GE group were significantly lower than in the GA group and GN group (P < 0.01). The intraoperative/total sufentanil dosage and remifentanil dosage in the GE group were significantly lower than those in the GA and GN groups (P < 0.01). The VAS scores in the GE group were significantly better than those in GA and GN groups (P < 0.01). General anesthesia combined with epidural anesthesia attenuates the increase in inflammatory mediators. Its possible mechanisms include reducing perioperative stress response and reducing perioperative opioid use.