Sphingolipid inhibitor response gene GhMYB86 controls fiber elongation by regulating microtubule arrangement.

Although the cell membrane and cytoskeleton play essential roles in cellular morphogenesis, the interaction between the membrane and cytoskeleton is poorly understood. Cotton fibers are extremely elongated single cells, which makes them an ideal model for studying cell development. Here, we used the sphingolipid biosynthesis inhibitor, fumonisin B1 (FB1), and found that it effectively suppressed the myeloblastosis (MYB) transcription factor GhMYB86, thereby negatively affecting fiber elongation. A direct target of GhMYB86 is GhTUB7, which encodes the tubulin protein, the major component of the microtubule cytoskeleton. Interestingly, both the overexpression of GhMYB86 and GhTUB7 caused an ectopic microtubule arrangement at the fiber tips, and then leading to shortened fibers. Moreover, we found that GhMBE2 interacted with GhMYB86 and that FB1 and reactive oxygen species induced its transport into the nucleus, thereby enhancing the promotion of GhTUB7 by GhMYB86. Overall, we established a GhMBE2-GhMYB86-GhTUB7 regulation module for fiber elongation and revealed that membrane sphingolipids affect fiber elongation by altering microtubule arrangement.

Obesity-enriched gut microbe degrades myo-inositol and promotes lipid absorption.

Numerous studies have reported critical roles for the gut microbiota in obesity. However, the specific microbes that causally contribute to obesity and the underlying mechanisms remain undetermined. Here, we conducted shotgun metagenomic sequencing in a Chinese cohort of 631 obese subjects and 374 normal-weight controls and identified a Megamonas-dominated, enterotype-like cluster enriched in obese subjects. Among this cohort, the presence of Megamonas and polygenic risk exhibited an additive impact on obesity. Megamonas rupellensis possessed genes for myo-inositol degradation, as demonstrated in vitro and in vivo, and the addition of myo-inositol effectively inhibited fatty acid absorption in intestinal organoids. Furthermore, mice colonized with M. rupellensis or E. coli heterologously expressing the myo-inositol-degrading iolG gene exhibited enhanced intestinal lipid absorption, thereby leading to obesity. Altogether, our findings uncover roles for M. rupellensis as a myo-inositol degrader that enhances lipid absorption and obesity, suggesting potential strategies for future obesity management.

Evodiamine encapsulated by hyaluronic acid modified zeolitic imidazolate framework-8 for tumor targeted therapy.

Evodiamine (EVO), a natural bioactive compound extracted from Evodia rutaecarpa, shows therapeutic ability against malignant melanoma. However, the poor solubility and bioavailability of EVO limit its clinical application. Metal-organic frameworks (MOFs) have shown excellent physical and chemical properties and are widely used as drug delivery systems. Among them, zeolitic imidazolate framework-8 (ZIF-8) is a research popular material because of its unique properties, such as hydrothermal stability, non-toxicity, biocompatibility, and pH sensitivity. In this study, in order to load EVO, a drug carrier that hyaluronic acid (HA) modified zeolitic imidazolate framework-8 (ZIF-8) is synthesized. This drug carrier has shown drug loading with 6.2 ± 0.6%, and the nano drugs (EVO@ZIF-8/HA) have good dispersibility. Owing to the decoration HA of EVO@ZIF-8, the potential of the nano drugs is reversed from the positive charge to the negative charge, which is beneficial to blood circulation in vivo. Furthermore, because the CD44-expressing in tumor cells is excessed, the endocytosis and accumulation of nano drugs in tumor cells are beneficial to improvement. Compared with free EVO, EVO@ZIF-8/HA has shown a significantly improved anti-tumor efficacy in vitro and in vivo. In summary, the drug carrier effectively addresses the challenges that are caused by the strong hydrophobicity and low bioavailability of EVO, thereby targeted tumor therapy of EVO can be achieved.

Bmi-1 promotes the proliferation, migration and invasion, and inhibits cell apoptosis of human retinoblastoma cells via RKIP.

Retinoblastoma is one of the most common ocular malignancies in children. Bmi-1, a member of the Polycomb group family of transcriptional repressors, is expressed in a variety of tumors. The purpose of our study was to explore the role of Bmi-1 in retinoblastoma. RT-qPCR and western blot were used for calculating the mRNA and protein levels of Bmi-1 and RKIP. MTT, Wound healing and Transwell assays were performed to measure the proliferation, migration and invasion in retinoblastoma cells. Cell apoptosis was detected by flow cytometry. The volume and mass of transplanted tumors were detected in nude mice. Bmi-1 was over expressed, and RKIP was low expressed in retinoblastoma cells. Bmi-1 promoted cell proliferation, migration and invasion and suppressed cell apoptosis of Y79 and SO-RB50 cells. Downregulation of Bmi-1 and overexpression of RKIP inhibited cell proliferation, migration and invasion, and increased cell apoptosis. The functions of Bmi-1 knockdown on retinoblastoma cells were blocked by RKIP knockdown, but promoted by RKIP. Down-regulated Bmi-1 inhibited xenograft tumor growth, and RKIP exacerbated this inhibitory effect. Bmi-1 served as a potential therapeutic target for improving the efficacy of clinical treatment in retinoblastoma. All the findings revealed the functions of Bmi-1/RKIP axis in retinoblastoma tumorigenesis.

The gut microbial composition in polycystic ovary syndrome with hyperandrogenemia and its association with steroid hormones.

Background: Polycystic ovary syndrome (PCOS) is characterized by excess androgens, ovulatory dysfunction, and polycystic ovaries. The mechanisms underlying ovulatory and metabolic disorders in PCOS remain elusive, hampering therapeutic development. Enhanced metabolic health correlates with increased microbiota gene content and microbial diversity. We aimed to explore the impact of gut microbiota and serum steroids on PCOS regulation associated with androgen excess. Methods: The fecal samples of patients with hyperandrogenic PCOS (n = 14) and control group with PCOS (n = 14) were analyzed by 16S rRNA gene sequencing. The peripheral venous blood of all subjects was collected to detect serum hormones. The association between gut microbiota and serum hormones was analyzed with the R language. Results: Our findings reveal that the hyperandrogenic PCOS group exhibits lower richness and diversity of gut microbiota compared to the control group. Characteristic genera in PCOS patients with hyperandrogenism include Bifidobacterium, Enterobacteriaceae_unclassified, Streptococcus, Saccharimonadaceae, Enterococcus, and Eubacterium_nodatum_group. Five hormones, including 5ß-androsterone, deoxycorticosterone, corticosterone, 11-dehydrocorticosterone, and cortexolone, emerge as potential serum biomarkers for identifying patients with hyperandrogenic-PCOS (HA-PCOS). Furthermore, a lower vitamin D3 level may act as a susceptibility factor, suggesting that vitamin D3 supplementation could serve as a potential intervention for PCOS with hyperandrogenism. Conclusion: Specific fecal microbiota and serum steroids may be used as characteristic markers for clinical diagnosis of hyperandrogenic-PCOS. This research enhances our understanding of the intricate interplay among hormones, gut microbiota, and hyperandrogenemia in patients with PCOS.

The Timing and Dose Effect of Acupuncture on Pregnancy Outcomes for Infertile Women Undergoing In Vitro Fertilization and Embryo Transfer: A Systematic Review and Meta-Analysis.

Background: Women undergoing in vitro fertilization and embryo transfer (IVF-ET) often utilize acupuncture to enhance pregnancy outcomes. Yet, the optimal timing for acupuncture sessions and the relationship between dosage and effect remain uncertain. Objectives: To investigate the impact of the timing and dosage of acupuncture on pregnancy outcomes, drawing on existing research. Methods: A comprehensive search of eight databases was conducted from their inception to January 14th, 2023, without restrictions on language. Only randomized controlled trials comparing acupuncture with either sham acupuncture or no adjuvant treatment were selected for inclusion. This meta-analysis assessed the efficacy of acupuncture in IVF-ET, analyzing the influence of varied timing and dosage on pregnancy outcomes. Subgroup analyses were undertaken to address any heterogeneity across the studies. Results: A total of 38 RCTs involving 5,991 participants were analyzed. In infertile women undergoing IVF fresh cycles, acupuncture performed during controlled ovarian hyperstimulation (COH) significantly increased the clinical pregnancy rate (CPR) (relative risk [RR] = 1.33, 95% confidence interval [CI]: 1.07-1.65, p = 0.01), whereas acupuncture administered either before COH or on the day of ET did not demonstrate reproductive benefits. Regarding frozen cycles, acupuncture before freeze-thaw embryo transfer (FET) significantly enhanced the CPR (RR = 1.71, 95% CI: 1.36-2.16, p < 0.00001) and live birth rate (LBR) (RR = 2.40, 95% CI: 1.20-4.79, p = 0.01). Improvements in CPR were observed across all dosage groups, but only the high-dosage group showed a significant increase in LBR (RR = 1.75, 95% CI: 1.05-2.92, p = 0.03). Conclusions: Timing and dosage of acupuncture are crucial factors affecting pregnancy outcomes in IVF-ET. For women undergoing IVF fresh cycles, acupuncture during COH yielded more significant reproductive benefits. In addition, acupuncture before freeze-thaw embryo transfer (FET) was associated with improved pregnancy outcomes in frozen cycles. Furthermore, higher dosages of acupuncture were linked to more favorable outcomes.

Diagnostic performance of volatile organic compounds analysis and electronic noses for detecting colorectal cancer: a systematic review and meta-analysis.

Introduction: The detection of Volatile Organic Compounds (VOCs) could provide a potential diagnostic modality for the early detection and surveillance of colorectal cancers. However, the overall diagnostic accuracy of the proposed tests remains uncertain. Objective: This systematic review is to ascertain the diagnostic accuracy of using VOC analysis techniques and electronic noses (e-noses) as noninvasive diagnostic methods for colorectal cancer within the realm of clinical practice. Methods: A systematic search was undertaken on PubMed, EMBASE, Web of Science, and the Cochrane Library to scrutinize pertinent studies published from their inception to September 1, 2023. Only studies conducted on human subjects were included. Meta-analysis was performed using a bivariate model to obtain summary estimates of sensitivity, specificity, and positive and negative likelihood ratios. The Quality Assessment of Diagnostic Accuracy Studies 2 tool was deployed for quality assessment. The protocol for this systematic review was registered in PROSPERO, and PRISMA guidelines were used for the identification, screening, eligibility, and selection process. Results: This review encompassed 32 studies, 22 studies for VOC analysis and 9 studies for e-nose, one for both, with a total of 4688 subjects in the analysis. The pooled sensitivity and specificity of VOC analysis for CRC detection were 0.88 (95% CI, 0.83-0.92) and 0.85 (95% CI, 0.78-0.90), respectively. In the case of e-nose, the pooled sensitivity was 0.87 (95% CI, 0.83-0.90), and the pooled specificity was 0.78 (95% CI, 0.62-0.88). The area under the receiver operating characteristic analysis (ROC) curve for VOC analysis and e-noses were 0.93 (95% CI, 0.90-0.95) and 0.90 (95% CI, 0.87-0.92), respectively. Conclusion: The outcomes of this review substantiate the commendable accuracy of VOC analysis and e-nose technology in detecting CRC. VOC analysis has a higher specificity than e-nose for the diagnosis of CRC and a sensitivity comparable to that of e-nose. However, numerous limitations, including a modest sample size, absence of standardized collection methods, lack of external validation, and a notable risk of bias, were identified. Consequently, there exists an imperative need for expansive, multi-center clinical studies to elucidate the applicability and reproducibility of VOC analysis or e-nose in the noninvasive diagnosis of colorectal cancer. Systematic review registration: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42023398465.

An approach to evaluating seasonal responses to acute toxicity of antibiotic nitrofurazone on periphytic ciliated protist communities in marine environments.

Periphytic protists including ciliates are the primary components of microbial communities in which they play a vital role in the progression of food webs by moving resources from lower to higher trophic levels. However, the toxic effects of veterinary antibiotics on periphytic protists across four seasons are minimally understood. Therefore, in this study, a 1-year survey was conducted with the antibiotic nitrofurazone (NFZ) applied at concentrations of 0.0, 1.5, 3.0, 6.0, and 12.0 mg/L. Samples of protist communities were collected using microscope glass slides during four seasons in the coastal waters of the Yellow Sea, Qingdao, northern China. The abundance of protists dropped with an increase in NFZ concentrations, and almost all species were dead at a concentration of 12.0 mg/L. The 12 h-LC50 values of NFZ for the protist biota were similar among the four seasons, despite significant seasonal variability in the community structure. The present results suggest that the periphytic protist biota may be used as a biomarker for assessing the ecotoxicity of NFZ in marine environments regardless of the year season.

The ARPKD Protein DZIP1L Regulates Ciliary Protein Entry by Modulating the Architecture and Function of Ciliary Transition Fibers.

Serving as the cell's sensory antennae, primary cilia are linked to numerous human genetic diseases when they malfunction. DZIP1L, identified as one of the genetic causes of human autosomal recessive polycystic kidney disease (ARPKD), is an evolutionarily conserved ciliary basal body protein. Although it has been reported that DZIP1L is involved in the ciliary entry of PKD proteins, the underlying mechanism remains elusive. Here, an uncharacterized role of DZIP1L is reported in modulating the architecture and function of transition fibers (TFs), striking ciliary base structures essential for selective cilia gating. Using C. elegans as a model, C01G5.7 (hereafter termed DZIP-1) is identified as the sole homolog of DZIP1L, which specifically localizes to TFs. While DZIP-1 or ANKR-26 (the ortholog of ANKRD26) deficiency shows subtle impact on TFs, co-depletion of DZIP-1 and ANKR-26 disrupts TF assembly and cilia gating for soluble and membrane proteins, including the ortholog of ADPKD protein polycystin-2. Notably, the synergistic role for DZIP1L and ANKRD26 in the formation and function of TFs is highly conserved in mammalian cilia. Hence, the findings illuminate an evolutionarily conserved role of DZIP1L in TFs architecture and function, highlighting TFs as a vital part of the ciliary gate implicated in ciliopathies ARPKD.

Cotton sphingosine kinase GhLCBK1 participates in fiber cell elongation by affecting sphingosine-1-phophate and auxin synthesis.

Sphingolipids serve as essential components of biomembrane and possess significant bioactive properties. Sphingosine-1-phophate (S1P) plays a key role in plant resistance to stress, but its specific impact on plant growth and development remains to be fully elucidated. Cotton fiber cells are an ideal material for investigating the growth and maturation of plant cells. In this study, we examined the content and composition of sphingosine (Sph) and S1P throughout the progression of fiber cell development. The content of S1P elevated gradually during fiber elongation but declined during the transition stage. Exogenous application of S1P promoted fiber elongation while using of FTY720 (an antagonist of S1P), and DMS (an inhibitor of LCBK) hindered fiber elongation. Cotton Long Chain Base Kinase 1 (GhLCBK1) was notably expressed during the fiber elongation stage, containing all conserved domains of LCBK protein and localized in the endoplasmic reticulum. Overexpression GhLCBK1 increased the S1P content and promoted fiber elongation while retarded secondary cell wall (SCW) deposition. Conversely, downregulation of GhLCBK1 reduced the S1P levels, and suppressed fiber elongation, and accelerated SCW deposition. Transcriptome analysis revealed that upregulating GhLCBK1 or applying S1P induced the expression of GhEXPANSIN and auxin related genes. Furthermore, the levels of IAA were elevated and reduced in the fibers when up-regulating or down-regulating GhLCBK1, respectively. Our investigation demonstrated that GhLCBK1 and its product S1P facilitated the elongation of fiber cells by affecting auxin biosynthesis. This study contributes novel insights into the intricate regulatory pathways involved in fiber cell elongation, identifying GhLCBK1 as a potential target gene and laying the groundwork for enhancing fiber quality via genetic manipulation.

Effects of thumb-tack needling combined with sporting on older adult patients with knee osteoarthritis: A randomized active-control clinical trial.

AIM: The aim of this clinical study was to explore the effects of thumb-tack needling combined with sporting (TTNS) therapy on the improvement of pain and joint function in older adult patients with knee osteoarthritis (KOA). METHODS: A total of 120 older adult patients with KOA were randomly assigned to receive TTNS therapy or medicine treatment (Med group) only for 1 month. The patients were followed up for 3 months and clinical efficacies were evaluated using a visual analog scale to assess pain, the Lequesne scoring system to assess motor function, and the Western Ontario and McMaster University Osteoarthritis Index to assess KOA severity. Blood was collected to measure the levels of interleukin-6 and tumor necrotic factor-alpha using enzyme-linked immunosorbent assay. RESULTS: The data suggested that TTNS therapy resulted in a significantly higher clinical efficacy (P = 0.012). Visual analog scale score, Lequesne index, and Western Ontario and McMaster University Osteoarthritis Index of the TTNS group at the time of post-treatment (1 month) and post-follow-up (3 months) were also lower compared with the Med group. Patients in the TTNS group also showed lower levels of serum tumor necrotic factor-alpha and interleukin-6. CONCLUSIONS: TTNS therapy is more efficacious than pharmacological treatment in improving the clinical outcomes of patients with KOA, which suggests its clinical utility in the management of KOA. Geriatr Gerontol Int 2024; 24: 415-420.

Meta-analysis of KAP toward COVID-19 in Chinese residents.

Background: During the coronavirus disease-2019 (COVID-19) pandemic, there have been many studies on knowledge, attitudes, and practices (KAP) toward prevention of COVID-19 infection in China. Except for symptomatic treatment and vaccination, KAP toward COVID-19 plays an important role in the prevention of COVID-19. There is no systematic evaluation and meta-analysis of KAP toward COVID-19 in China. This study is the earliest meta-analysis of KAP toward COVID-19 in China's general population. Hence, this systematic review aimed to summarize the knowledge, attitudes, and practices (KAP) of Chinese residents toward COVID-19 during the pandemic. Methodology: Following the PRISMA guidelines, articles relevant to COVID-19 KAP that were conducted among the Chinese population were found in databases such as Scopus, ProQuest, PubMed, EMbase, Web of Science, Cochrane Library, China Biology Medicine, China National Knowledge Infrastructure, CQVIP, Wanfang and Google Scholar. A random-effect meta-analysis is used to summarize studies on knowledge, attitudes, and practice levels toward COVID-19 infection in China's general population. Results: Fifty-seven articles published between August 2020 and November 2022 were included in this review. Overall, 75% (95% CI: 72-79%) of Chinese residents had good knowledge about COVID-19, 80% (95% CI: 73-87%) of Chinese residents had a positive attitude toward COVID-19 pandemic control and prevention (they believe that Chinese people will win the battle against the epidemic), and the aggregated proportion of residents with a correct practice toward COVID-19 was 84% (95% CI: 82-87%, I2 = 99.7%).In the gender subgroup analysis, there is no significant difference between Chinese men and Chinese women in terms of their understanding of COVID-19. However, Chinese women tend to have slightly higher levels of knowledge and a more positive attitude toward the virus compared to Chinese men. When considering the urban and rural subgroup analysis, it was found that Chinese urban residents have a better understanding of COVID-19 compared to Chinese rural residents. Interestingly, the rural population displayed higher rates of correct behavior and positive attitudes toward COVID-19 compared to the urban population. Furthermore, in the subgroup analysis based on different regions in China, the eastern, central, and southwestern regions exhibited higher levels of knowledge awareness compared to other regions. It is worth noting that all regions in China demonstrated good rates of correct behavior and positive attitudes toward COVID-19. Conclusion: This study reviews the level of KAP toward COVID-19 during the pandemic period in China. The results show that the KAP toward COVID-19 in Chinese residents was above a favorable level, but the lack of translation of knowledge into practice should be further reflected on and improved. A subgroup analysis suggests that certain groups need more attention, such as males and people living in rural areas. Policy makers should pay attention to the results of this study and use them as a reference for the development of prevention and control strategies for major public health events that may occur in the future. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=348246, CRD42022348246.

Cep131-Cep162 and Cby-Fam92 complexes cooperatively maintain Cep290 at the basal body and contribute to ciliogenesis initiation.

Cilia play critical roles in cell signal transduction and organ development. Defects in cilia function result in a variety of genetic disorders. Cep290 is an evolutionarily conserved ciliopathy protein that bridges the ciliary membrane and axoneme at the basal body (BB) and plays critical roles in the initiation of ciliogenesis and TZ assembly. How Cep290 is maintained at BB and whether axonemal and ciliary membrane localized cues converge to determine the localization of Cep290 remain unknown. Here, we report that the Cep131-Cep162 module near the axoneme and the Cby-Fam92 module close to the membrane synergistically control the BB localization of Cep290 and the subsequent initiation of ciliogenesis in Drosophila. Concurrent deletion of any protein of the Cep131-Cep162 module and of the Cby-Fam92 module leads to a complete loss of Cep290 from BB and blocks ciliogenesis at its initiation stage. Our results reveal that the first step of ciliogenesis strictly depends on cooperative and retroactive interactions between Cep131-Cep162, Cby-Fam92 and Cep290, which may contribute to the complex pathogenesis of Cep290-related ciliopathies.

The Impact of Ultrasound-Guided Combined with Water and Air Mixed Injection Method for Nasal Intestinal Tube Placement on Gastrointestinal Burden in Patients with Severe Acute Pancreatitis.

Objective: This study aims to investigate the impact of ultrasound-guided combined with water and air mixed injection method for nasal intestinal tube placement on gastrointestinal burden in patients with severe acute pancreatitis. Methods: A cohort of 116 patients with severe acute pancreatitis admitted to the hospital from August 2021 to July 2023 were included. They were randomly divided into the control group (58 cases, nasal intestinal tube placement using ultrasound-guided combined water injection) and the observation group (58 cases, nasal intestinal tube placement using ultrasound-guided combined with water and air mixed injection). The incubation time, volume of water injected during the incubation, nasal intestinal tube visualization rate, and success rate of one-time incubation were recorded for both groups. Gastrointestinal mucosal barrier function, Nutritional index level including intestinal fatty acid-binding protein (I-FABP), D-lactate and nutritional index levels including hemoglobin (Hb), serum albumin (ALB), retinol-binding protein (RBP) were compared between the two groups before tube placement and at 7 days after incubation. Complications in both groups were also recorded. Results: The incubation time in the observation group was shorter, and the volume of water injected during the incubation was lower than in the control group. The nasal intestinal tube visualization rate and success rate of one-time incubation were higher in the observation group (P < .05). At 7 days after incubation, the levels of I-FABP and D-lactate were lower in the observation group than in the control group (P < .05). At 7 days after incubation, The levels of I-FABP and D-lactate in the observation group were lower than those in the control group, Hb and RBP levels were higher in the observation group than in the control group (P < .05), while there was no significant difference in ALB levels between the two groups (P > .05). The incidence of complications was lower in the observation group than in the control group (P < .05). Conclusion: Ultrasound-guided combined with water and air mixed injection method for nasal intestinal tube placement in patients with severe acute pancreatitis can shorten the incubation time, reduce the volume of water injected during the incubation, improve the nasal intestinal tube visualization rate and success rate of one-time incubation, enhance gastrointestinal mucosal barrier function and nutritional index in patients, and reduce the incidence of complications.

Gypenoside induces apoptosis by inhibiting the PI3K/AKT/mTOR pathway and enhances T-cell antitumor immunity by inhibiting PD-L1 in gastric cancer.

Introduction: Gypenoside is a natural extract of Gynostemma pentaphyllum (Thunb.) Makino, a plant in the Cucurbitaceae family. It has been reported to have antitumor effects on the proliferation, migration and apoptosis of various types of cancer cells. However, the use of gypenoside in the treatment of gastric cancer has not been studied. In the present study, we explored the therapeutic effect of gypenoside on gastric cancer and the potential molecular mechanism. Methods and Results: Our results showed that gypenoside induced apoptosis in HGC-27 and SGC-7901 cells in a time-dependent and dose-dependent manner. Network pharmacology analyses predicted that gypenoside exerts its therapeutic effects through the PI3K/AKT/mTOR signaling pathway. Furthermore, molecular docking and western blot experiments confirmed that gypenoside induced the apoptosis of gastric cancer cells through the PI3K/AKT/mTOR signaling pathway. In addition, network pharmacological analysis revealed that the common targets of gypenoside in gastric cancer were enriched in the immune effector process, PD-L1 expression, the PD-1 checkpoint pathway, and the Jak-STAT signaling pathway. Furthermore, molecular docking and western blot assays demonstrated that gypenoside could bind to STAT3 and reduce its phosphorylation. Thus, the transcription of PD-L1 was inhibited in gastric cancer cells. Moreover, coculture experiments of gastric cancer cells with gypenoside and primary mouse CD8+ T cells showed that gastric cancer cells treated with gypenoside could enhance the antitumor ability of T cells. Animal experiments confirmed the antitumor effect of gypenoside, and the expression of PD-L1 was significantly downregulated in the gypenoside-treated group. Conclusion: Gypenoside induced the apoptosis of gastric cancer cells by inhibiting the PI3K/AKT/mTOR pathway and simultaneously inhibited the expression of PD-L1 in gastric cancer cells, thus enhancing the antitumor immunity of T cells. This study provides a theoretical basis for applying gypenoside as a new therapeutic agent to enhance the efficacy of immunotherapy in gastric cancer.

Effects of continuous warming on homogeneity of periphytic protozoan fauna in marine ecosystems.

As a powerful biological indicator, multivariate dispersion in a community is widely used to evaluate the biological evaluation of environmental heterogeneity. To investigate the effects of persistent warming on microbial fauna in marine environments, the periphytic protozoan communities were used as test organisms and incubated in five temperature-controlled circulation system at 22 (control), 25, 28, 31 and 34 °C, respectively. The results showed that (1) there was a clear variation in species occurrence, and the α-/γ-diversity measures decreased with the increase of temperatures; (2) the compositional pattern was significantly driven by the persistent warming compared to community pattern from species-abundance data; and (3) both traditional ß-diversity and multivariate dispersion measures on species compositional matrix were significantly correlative with changes in the temperature. Therefore, it is suggested that continuous temperature fluctuations have a greater impact on homogeneity of species composition of protozoan communities than that of their community structure.

Tozasertib activates anti-tumor immunity through decreasing regulatory T cells in melanoma.

Although immune checkpoint therapy has significantly improved the prognosis of patients with melanoma, urgent attention still needs to be paid to the low patient response rates and the challenges of precisely identifying patients before treatment. Therefore, it is crucial to investigate novel immunosuppressive mechanisms and targets in the tumor microenvironment in order to reverse tumor immune escape. In this study, we found that the cell cycle checkpoint Aurora kinase B (AURKB) suppressed the anti-tumor immune response, and its inhibitor, Tozasertib, effectively activated T lymphocyte cytokine release in vitro and anti-tumor immunity in vivo. Tozasertib significantly inhibited melanoma xenograft tumor growth by decreasing the number of inhibitory CD4+ Treg cells in the tumors, which, in turn, activated CD8+ T cells. Single-cell analysis revealed that AURKB suppressed anti-tumor immunity by increasing MIF-CD74/CXCR4 signaling between tumor cells and lymphocytes. Our study suggests that AURKB is a newly identified anti-tumor immunity suppressor, whose inhibitors may be developed as novel anti-tumor immunity drugs and may have synergistic anti-melanoma effects with immune checkpoint therapies.

Microplastics drive community dynamics of periphytic protozoan fauna in marine environments.

The pollution of microplastics (MPs) to the marine environment has become a widespread focus of attention. To assess MP-induced ecotoxicity on marine ecosystems, periphytic protozoan communities were used as test organisms and exposed to five concentrations of MPs: 0, 1, 5, 25, and 125 mg l-1. Protozoan samples were collected using microscope slides from coastal waters of the Yellow Sea, northern China. A total of 13 protozoan species were identified and represented different tolerance to MP-induced ecotoxicity. Inhibition effects of MPs on the test protozoan communities were clearly shown in terms of both the species richness and individual abundance and followed linear relationships to MP concentrations. The community patterns were driven by MPs and significantly shifted at concentrations over 5 mg l-1. Our findings demonstrated that MPs may induce the community-level ecotoxic response of periphytic protozoan fauna and followed significant community dynamics. Thus, it is suggested that periphytic protozoan fauna may be used as useful community-based test model organisms for evaluating MP-induced ecotoxicity in marine environments.

Chinese herbal medicine for irinotecan-induced diarrhea: A systematic review and meta-analysis.

INTRODUCTION: Irinotecan is a novel first-line therapy for colorectal cancer, but the toxicity and side effects include diarrhea without satisfactory treatments. Chinese herbal decoction (CHD) is an effective complementary and alternative prevention and therapy for irinotecan induced diarrhea (IID). This systematic review and meta-analysis of randomized controlled trials (RCTs) aims to assess the preventive effect of CHD in the treatment of IID. METHODS: Seven databases (PubMed, COCHRANE, EMBASE, CNKI, VIP, Wanfang, and CBM) were screened for random controlled trials on the prevention and treatment of IID by CHD from January 1980 to May 2022. The Cochrane Collaboration Risk of Bias (ROB 2.0) was applied for bias risk assessment, and the Grading Recommendation Assessment, Development, and Evaluation (GRADE) for quality of evidence. Meta-analysis was conducted with RevMan 5.3 software. In addition, a subgroup analysis was conducted on different grades of diarrhea, the incidence and duration of diarrhea, the selection of specific Chinese herbal medicine decoction, and the incidence of adverse reactions. Risk ratios (RR) and 95% confidence intervals (CIs) were calculated for all data by combining the meta-analysis with fixed or random-effects models based on outcome heterogeneity. RESULTS: Fourteen RCTs involving 1056 participants were included. The study results displayed that the incidence of IID was lower with the use of CHD than the no-treatment group (RR = 0.55, 95% CI = 0.40-0.75, P = 0.0002). CHD in combination with western medicine (WM) was more effective than WM alone for IID (RR = 0.44, 95% CI 0.23-0.84, P = 0.01). This protective effect was more pronounced for severe grade III-V diarrhea (RR = 0.41, 95% CI = 0.26-0.64, P < 0.0001). In the specific Chinese herbal medicine decoction, the Banxia Xie Xin decoction presented better effectiveness (RR = 0.18, 95% CI: 0.05-0.63, P = 0.007) than WM alone. The Huangqin decoction was the most widely studied interventional scheme (n = 5). The relative risk (RR) of the Huangqin decoction was 0.56. No obvious adverse reactions were observed. CONCLUSION: This study demonstrated that CHD has a preventive effect on IID and could be used as a complementary therapy with few side effects. However, additional large-sample, high-quality, randomized, double-blind trials are needed to guide the clinical practice scientifically. SYSTEMATIC REVIEW REGISTRATION: www.crd.york.ac.uk/prospero (NO: CRD42020189506).

Bacteroides methylmalonyl-CoA mutase produces propionate that promotes intestinal goblet cell differentiation and homeostasis.

Propionate is a short-chain fatty acid that is generated upon microbiome-mediated fiber fermentation in the intestine. By modulating immune and metabolic pathways, propionate exerts many health benefits. Key bacterial species, such as Bacteroides thetaiotaomicron, generate propionate, but the biochemical pathways and specific functions remain undetermined. We identified a gene operon-encoding methylmalonyl-CoA mutase (MCM) that contributes to propionate biosynthesis in B. thetaiotaomicron. Colonization of germ-free mice with wild-type or MCM-deficient strains as well as in vitro examination demonstrated that MCM-mediated propionate production promotes goblet cell differentiation and mucus-related gene expression. Intestinal organoids lacking the propionate receptor, GPR41, showed reduced goblet cell differentiation upon MCM-mediated propionate production. Furthermore, although wild-type B. thetaiotaomicron alleviated DSS-induced intestinal inflammation, this effect was abolished in mice receiving the MCM-deficient strain but restored upon propionate supplementation. These data emphasize the critical role of MCM-mediated propionate biosynthesis in goblet cell differentiation, offering potential pathways to ameliorate colitis.