Direction of leukocyte polarization and migration by the phosphoinositide-transfer protein TIPE2.

The polarization of leukocytes toward chemoattractants is essential for the directed migration (chemotaxis) of leukocytes. How leukocytes acquire polarity after encountering chemical gradients is not well understood. We found here that leukocyte polarity was generated by TIPE2 (TNFAIP8L2), a transfer protein for phosphoinositide second messengers. TIPE2 functioned as a local enhancer of phosphoinositide-dependent signaling and cytoskeleton remodeling, which promoted leading-edge formation. Conversely, TIPE2 acted as an inhibitor of the GTPase Rac, which promoted trailing-edge polarization. Consequently, TIPE2-deficient leukocytes were defective in polarization and chemotaxis, and TIPE2-deficient mice were resistant to leukocyte-mediated neural inflammation. Thus, the leukocyte polarizer is a dual-role phosphoinositide-transfer protein and represents a potential therapeutic target for the treatment of inflammatory diseases.

Transcriptome disclosure of hormones inducing stigma exsertion in Nicotiana tabacum by corolla shortening.

BACKGROUND: Stigma exsertion is an essential agricultural trait that can promote cross-pollination to improve hybrid seed production efficiency. However, the molecular mechanism controlling stigma exsertion remains unknown. RESULTS: In this study, the Nicotiana tabacum cv. K326 and its two homonuclear-heteroplasmic lines, MSK326 (male-sterile) and MSK326SE (male-sterile and stigma exserted), were used to investigate the mechanism of tobacco stigma exsertion. A comparison of the flowers between the three lines showed that the stigma exsertion of MSK326SE was mainly due to corolla shortening. Therefore, the corollas of the three lines were sampled and presented for RNA-seq analysis, which found 338 candidate genes that may cause corolla shortening. These genes were equally expressed in K326 and MSK326, but differentially expressed in MSK326SE. Among these 338 genes, 15 were involved in hormone synthesis or signal transduction pathways. Consistently, the content of auxin, dihydrozeatin, gibberellin, and jasmonic acid was significantly decreased in the MSK326SE corolla, whereas abscisic acid levels were significantly increased. Additionally, seven genes involved in cell division, cell cycle, or cell expansion were identified. Protein-protein interaction network analysis identified 45 nodes and 79 protein interactions, and the largest module contained 20 nodes and 52 protein interactions, mainly involved in the hormone signal transduction and pathogen defensive pathways. Furthermore, a putative hub gene coding a serine/threonine-protein kinase was identified for the network. CONCLUSIONS: Our results suggest that hormones may play a key role in regulating tobacco stigma exsertion induced by corolla shortening.

Overexpression of the WRKY transcription factor gene NtWRKY65 enhances salt tolerance in tobacco (Nicotiana tabacum).

BACKGROUND: Salt stress severely inhibits plant growth, and the WRKY family transcription factors play important roles in salt stress resistance. In this study, we aimed to characterize the role of tobacco (Nicotiana tabacum) NtWRKY65 transcription factor gene in salinity tolerance. RESULTS: This study characterized the role of tobacco (Nicotiana tabacum) NtWRKY65 transcription factor gene in salinity tolerance using four NtWRKY65 overexpression lines. NtWRKY65 is localized to the nucleus, has transactivation activity, and is upregulated by NaCl treatment. Salinity treatment resulted in the overexpressing transgenic tobacco lines generating significantly longer roots, with larger leaf area, higher fresh weight, and greater chlorophyll content than those of wild type (WT) plants. Moreover, the overexpressing lines showed elevated antioxidant enzyme activity, reduced malondialdehyde content, and leaf electrolyte leakage. In addition, the Na+ content significantly decreased, and the K+/Na+ ratio was increased in the NtWRKY65 overexpression lines compared to those in the WT. These results suggest that NtWRKY65 overexpression enhances salinity tolerance in transgenic plants. RNA-Seq analysis of the NtWRKY65 overexpressing and WT plants revealed that NtWRKY65 might regulate the expression of genes involved in the salt stress response, including cell wall component metabolism, osmotic stress response, cellular oxidant detoxification, protein phosphorylation, and the auxin signaling pathway. These results were consistent with the morphological and physiological data. These findings indicate that NtWRKY65 overexpression confers enhanced salinity tolerance. CONCLUSIONS: Our results indicated that NtWRKY65 is a critical regulator of salinity tolerance in tobacco plants.

Transcription factors NtHD9 and NtHD12 control long glandular trichome formation via jasmonate signaling.

Glandular trichomes are universal epidermal structures that produce abundant specialized metabolites. However, knowledge of the initiation of glandular heads in glandular trichomes is limited. Herein, we found an intrinsic link of morphogenesis between glandular trichomes and non-glandular trichomes. Two novel homeodomain leucine zipper II members in tobacco (Nicotiana tabacum), NtHD9 and NtHD12, played important roles in long glandular trichome formation: NtHD9 was responsible for glandular head formation, while NtHD12 simultaneously controlled the formation of stalks and glandular heads. DAP-seq analysis suggested that NtHD9 can bind to the KKGCATTWAWTR motif of the cytochromes P450 94C1 (NtCYP94C1) promoter, which is involved in jasmonoyl-isoleucine oxidation. RNA-seq analysis of non-transformed tobacco and nthd9 plants revealed that NtHD9 modulates the expression of jasmonate (JA) signaling- and six trichome development-related genes. Notably, MeJA treatment restored the morphogenesis of long glandular trichomes in nthd9 and nthd12 plants, and the size of glandular heads increased with increasing MeJA concentration. However, the phenotype of long glandular trichome absence in double mutants of NtHD9 and NtHD12 could not be restored by MeJA. Our data demonstrate that NtHD9 and NtHD12 have distinct major functions yet overlapping roles in long glandular trichome formation via JA signaling.

Analysis of the clinical profile and treatment efficiency of hyperlipidemic acute pancreatitis.

BACKGROUND: The incidence of hyperlipidemic acute pancreatitis (HLAP) has been increasing annually. However, population-based morbidity assessments need to be updated. Early, rapid, and effective lipid-lowering may minimize pancreatic injury and improve clinical prognosis. It is essential to choose the proper treatment. However, treatment options for HLAP are controversial, and there is no uniform treatment protocol. METHODS: In this retrospective study, 127 patients with hyperlipidemic severe acute pancreatitis (HL-SAP) were registered from January 2018 to December 2022 at the General Hospital of Ningxia Medical University. Medical and radiological records of hospitalized patients were collected to determine clinical features, severity, complications, mortality, recurrence rate, and treatment. Risk factors for HL-SAP were analyzed using multifactorial logistic regression. A propensity score matching method was used to compare the clinical outcomes of standard and plasma exchange therapies. RESULTS: In this research, the prevalence of HLAP increased about 1.6 times, and the prevalence of HL-SAP was 50.60%. HL-SAP occurs most often in people between the ages of 30 and 39. Amylase exceeded 110 U/L in 84.3% of patients and 330 U/L in only 47.2%. 83.5% of HL-SAP patients had fatty livers and high body mass index (BMI). A total of 48.0% of patients experienced organ failure, ICU treatment (55.1%), recurrence (33.1%), and death (21.3%). Between the hyperlipidemic group and the biliary group in terms of age, gender, BMI, fatty liver, pleural effusion, abdominal constriction syndrome (ACS), multiple organ dysfunction syndrome (MODS), length of hospital, medical costs, morbidity and mortality, triglyceride, cholesterol, creatinine, blood glucose, D-dimer, amylase, albumin, lactate dehydrogenase, serum phosphorus, serum calcium, oxygenation index, and recurrence rate were statistically significant (P < 0.05). High BMI (P = 0.0038, odds ratio (OR) = 1.336, 95%CI: 0.99-1.804), high C-reactive protein (CRP) (P = 0.022, OR = 1.011, 95%CI: 1.003-1.019), low calcium (P = 0.003, OR = 0.016, 95%CI. 0.001-0.239), low albumin (P = 0.012, OR = 0.045, 95%CI: -0.062-0.192), and high D-dimer (P = 0.041, OR = 0.619, 95%CI: 0.053-2.510) were risk factors for HL-SAP, according to multifactorial logistic regression analysis. Adjusted for propensity score matching (PSM), Serum triglyceride (TG) was significantly lower in both the standard treatment (P < 0.001) and plasma exchange (P < 0.001) groups at 48 h compared with the initial test after the attack. Clearance (83.20% ± 0.0% vs. 84.4% ± 0.0%, P = 0.531), length of hospital stay (19.9 ± 4.9 vs. 19.8 ± 11.1, P = 0.092), and death (26.3% vs. 23.6%, P = 0.791) showed no difference between the two groups. However, the difference in medical costs(P = 0.039)between the two groups was statistically significant. CONCLUSION: The incidence of HLAP exhibited a significant increase, remarkable severity, recurrent trend, and mortality. High BMI, high CRP, low calcium, low albumin, and high D-dimer are risk factors for HL-SAP. Compared with standardized treatment, plasma exchange does not improve the prognosis of HL-SAP patients, and standardized treatment is equally effective, safe, and low-cost in early treatment.

Assessing trends and burden of occupational exposure to asbestos in the United States: a comprehensive analysis from 1990 to 2019.

BACKGROUND: This study aimed to analyze the trends and burden of occupational exposure to asbestos in the United States (U.S.) from 1990 to 2019, focusing on mortality rates, geographic distribution, age and sex patterns, and causes of death. METHODS: Data on the number of deaths attributable to occupational exposure to asbestos were collected from 1990 to 2019 in the U.S. Joinpoint analysis was conducted to assess trends over time, and regression models were applied to calculate annual percentage changes (APC) and annual average percentage changes (AAPC). Geographic distribution was examined using mapping techniques. Age and sex patterns were analyzed, and causes of death were identified based on available data. RESULTS: From 1990 to 2019, the overall number of deaths due to occupational exposure to asbestos in the U.S. increased by 20.2%. However, age-standardized mortality rates (ASMR) and age-standardized disability-adjusted life years (DALYs) rates (ASDR) exhibited a decline over the same period. Geographic analysis revealed differences in the number of deaths across states in 2019, with California reporting the highest number of fatalities. Age-specific mortality and DALYs showed an increase with age, peaking in older age groups. Tracheal, bronchus, and lung cancer were the leading causes of death attributed to asbestos exposure, with increasing trends observed over the past five years. CONCLUSION: The study highlights significant trends and burden in occupational exposure to asbestos in the U.S., including overall increases in mortality rates, declining ASMR and ASDR, geographic disparities, age and sex patterns, and shifts in causes of death. These findings underscore the importance of continued monitoring and preventive measures to mitigate the burden of asbestos-related diseases.

Intermittent fasting and Alzheimer's disease-Targeting ketone bodies as a potential strategy for brain energy rescue.

Alzheimer's disease (AD) lacks effective clinical treatments. As the disease progresses, the cerebral glucose hypometabolism that appears in the preclinical phase of AD gradually worsens, leading to increasingly severe brain energy disorders. This review analyzes the brain energy deficit in AD and its etiology, brain energy rescue strategies based on ketone intervention, the effects and mechanisms of IF, the differences in efficacy between IF and ketogenic diet and the duality of IF. The evidence suggests that brain energy deficits lead to the development and progression of AD pathology. IF, which improves brain energy impairments by promoting ketone metabolism, thus has good therapeutic potential for AD.

Optimizing the algae-bacteria biofilm reactor for imidacloprid wastewater treatment: An evaluation of hydraulic retention times for enhanced efficiency and energy savings.

Recent observations have highlighted the rapidly growing prevalence of emerging contaminants such as Imidacloprid (IMI) within our environment. These insecticidal pollutants, coexisting with more traditional contaminants, have become predominant in aquatic systems, posing risks to both human and ecological well-being. Among the various wastewater treatment approaches tested, biofilm reactors are currently gaining prominence. In this study, we employed an Algae-Bacteria Biofilm Reactor (ABBR) to concurrently address both conventional and emergent contaminants, specifically IMI, over an extended timeframe. Following a 60-day assessment, the ABBR consistently demonstrated removal efficiencies exceeding 85% for total dissolved nitrogen, ammonia nitrogen, and total dissolved phosphorus, and also achieved removal efficacy for the soluble chemical oxygen demand (sCOD). Despite the removal efficiency of IMI (with initial concentration is 1.0 mg/L) in ABBR showed a gradual decline over the extended period, it remained consistently effective over 50% due to the microalgae-mediated free radical reactions, indicating the ABBR's sustained efficiency in long-duration operations. Additionally, applying some non-conventional modifications, like aeration removal and reducing light exposure, demonstrated minimal impact on the reactor's pollutant removal efficiencies, achieving comparable results to the control group (which utilized aeration with a 14:10 light/dark ratio), 0.92 kW h/L/d of electricity can be saved economically, which accentuated the potential for energy conservation. An in-depth analysis of the treated effluents from the ABBRs, using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technique, uncovered four potential transformation pathways for IMI. Overall, our findings suggest that these optimized processes did not influence the transformation products of IMI, thereby reaffirming the viability of our proposed optimization.

A retrospective investigation on clinical and radiographic outcomes of distal tibial fractures after intramedullary nailing using the lateral parapatellar extra-articular approach.

INTRODUCTION: According to reports, the modified extra-articular parapatellar approach allows the performance of tibial nailing in the semi-extended position without the concern of joint violation. However, there remains no special study that has provided a detailed assessment of the benefits and risks of this approach for treating distal tibial fractures (DTFs). The aim of this retrospective study was to investigate the clinical and radiological outcomes of patients with DTFs after intramedullary nailing using a lateral parapatellar extra-articular (LPE) approach in comparison to using the suprapatellar (SP) and transpatellar (TP) approaches. METHODS: Data were collected from 99 patients with a minimum follow-up period of 12 months. Comparisons were conducted between the groups regarding the number of intraoperative fluoroscopies, complications, knee pain, knee range of motion (ROM), the Lysholm Knee Scale (LKS), the Olerud-Molander Ankle Score (OMAS) and radiological findings. RESULTS: The demographic characteristics were comparable between the groups. Fewer intraoperative fluoroscopies were performed in the LPE (27.47 ± 4.98) and SP (26.03 ± 5.12) groups than in the TP group (30.20 ± 7.42; P<0.001). When compared with the other two approaches, the LPE approach was associated with less knee pain (P<0.001) and better knee ROM (P<0.001) at one week postoperative. No significant intergroup differences were detected in the incidence of complications, LKS scores (P = 0.687) and OMAS (P = 0.926). Radiological findings demonstrated that postoperative tibial alignment (P = 0.853), the time of bony union and rate of non-union were similar between the groups. CONCLUSION: The LPE approach can serve as a safe and effective option for tibial nailing, as it offers favourable outcomes in knee pain relief and knee ROM in the early postoperative period and is equivalent to the other two approaches in terms of the incidence of complications, fracture healing, functional recovery and postoperative alignment for patients with DTFs.

Mitophagy suppression by miquelianin-rich lotus leaf extract induces 'beiging' of white fat via AMPK/DRP1-PINK1/PARKIN signaling axis.

BACKGROUND: Lotus (Nelumbo nucifera) leaf has been described to have anti-obesity activity, but the role of white fat 'browning' or 'beiging' in its beneficial metabolic actions remains unclear. Here, 3T3-L1 cells and high-fat-diet (HFD)-fed mice were used to evaluate the effects of miquelianin-rich lotus leaf extract (LLE) on white-to-beige fat conversion and its regulatory mechanisms. RESULTS: Treatment with LLE increased mitochondrial abundance, mitochondrial membrane potential and NAD+ /NADH ratio in 3T3-L1 cells, suggesting its potential in promoting mitochondrial activity. qPCR and/or western blotting analysis confirmed that LLE induced the expression of beige fat-enriched gene signatures (e.g. Sirt1, Cidea, Dio2, Prdm16, Ucp1, Cd40, Cd137, Cited1) and mitochondrial biogenesis-related markers (e.g. Nrf1, Cox2, Cox7a, Tfam) in 3T3-L1 cells and inguinal white adipose tissue of HFD-fed mice. Furthermore, we found that LLE treatment inhibited mitochondrial fission protein DRP1 and blocked mitophagy markers such as PINK1, PARKIN, BECLIN1 and LC-3B. Chemical inhibition experiments revealed that AMPK/DRP1 signaling was required for LLE-induced beige fat formation via suppressing PINK1/PARKIN/mitophagy. CONCLUSION: Our data reveal a novel mechanism underlying the anti-obesity effect of LLE, namely the induction of white fat beiging via AMPK/DRP1/mitophagy signaling. © 2023 Society of Chemical Industry.

Diallyl trisulfide alleviates chemotherapy sensitivity of ovarian cancer via the AMPK/SIRT1/PGC1α pathway.

Platinum-based chemotherapy promotes drug resistance in ovarian cancer. We investigated the antichemoresistance characteristics of diallyl trisulfide (DATS) in cisplatin-resistant ovarian cancer cells, in vitro and in vivo. Previous preclinical studies have revealed that DATS regulates distinct hallmark cancer-signaling pathways. The cell cycle pathway is the most investigated signaling pathway in DATS. Additionally, post-DATS treatment has been found to promote proapoptotic capacity through the regulation of intrinsic and extrinsic apoptotic pathway components. In the present study, we found that treating cisplatin-sensitive and cisplatin-resistant ovarian cell lines with DATS inhibited their proliferation and reduced their IC50. It induced cell apoptosis and promoted oxidative phosphorylation through the regulation of the AMPK/SIRT1/PGC1α pathway, OXPHOS, and enhanced chemotherapy sensitivity. DATS treatment alleviated glutamine consumption in cisplatin-resistant cells. Our findings highlight the role of DATS in overcoming drug resistance in ovarian cancer in vitro and in vivo. In addition, we elucidated the role of the AMPK/SIRT1/PGC1α signaling pathway as a potential target for the treatment of drug-resistant ovarian cancer.

Prospective randomized comparison between upgraded '2C3L' vs. PVI approach for catheter ablation of persistent atrial fibrillation: PROMPT-AF trial design.

BACKGROUND: In randomized studies, the strategy of pulmonary vein antral isolation (PVI) plus linear ablation has failed to increase success rates for persistent atrial fibrillation (PeAF) ablation when compared with PVI alone. Peri-mitral reentry related atrial tachycardia due to incomplete linear block is an important cause of clinical failures of a first ablation procedure. Ethanol infusion (EI) into the vein of Marshall (EI-VOM) has been demonstrated to facilitate a durable mitral isthmus linear lesion. OBJECTIVE: This trial is designed to compare arrhythmia-free survival between PVI and an ablation strategy termed upgraded '2C3L' for the ablation of PeAF. STUDY DESIGN: The PROMPT-AF study (clinicaltrials.gov 04497376) is a prospective, multicenter, open-label, randomized trial using a 1:1 parallel-control approach. Patients (n = 498) undergoing their first catheter ablation of PeAF will be randomized to either the upgraded '2C3L' arm or PVI arm in a 1:1 fashion. The upgraded '2C3L' technique is a fixed ablation approach consisting of EI-VOM, bilateral circumferential PVI, and 3 linear ablation lesion sets across the mitral isthmus, left atrial roof, and cavotricuspid isthmus. The follow-up duration is 12 months. The primary end point is freedom from atrial arrhythmias of >30 seconds, without antiarrhythmic drugs, in 12 months after the index ablation procedure (excluding a blanking period of 3 months). CONCLUSIONS: The PROMPT-AF study will evaluate the efficacy of the fixed '2C3L' approach in conjunction with EI-VOM, compared with PVI alone, in patients with PeAF undergoing de novo ablation.

Multi-omics profiling of PC-3 cells reveals bufadienolides-induced lipid metabolic remodeling by regulating long-chain lipids synthesis and hydrolysis.

INTRODUCTION: Lipid metabolism participates in various biological processes such as proliferation, apoptosis, migration, invasion, and maintenance of membrane homeostasis of prostate tumor cells. Bufadienolides, the active ingredients of Chansu, show a robust anti-proliferative effect against prostate cancer cells in vitro, but whether bufadienolides could regulate the lipid metabolism in prostate cancer has not been evaluated. OBJECTIVES: Our study explored the regulatory effects of bufadienolides on lipid metabolism in human prostate carcinoma cells (PC-3). METHODS: Untargeted lipidomics and transcriptomics were combined to study the effect of different bufadienolides interventions on lipid and gene changes of PC-3 cells. The key genes related to lipid metabolism and prostate cancer development were verified by qPCR and western blotting. RESULTS: Lipidomic analysis showed that the active bufadienolides significantly downregulated the content of long-chain lipids of PC-3 cells. Based on transcriptomic and qPCR analyses, many genes related to lipid metabolism were significantly regulated by active bufadienolides, such as ELOVL6, CYP2E1, GAL3ST1, CERS1, PLA2G10, PLD1, SPTLC3, and GPX2. Bioinformatics analysis of the Cancer Genome Atlas database and literature retrieval showed that elongation of very long-chain fatty acids protein 6 (ELOVL6) and phospholipase D1 (PLD1) might be important regulatory genes. Western blot analysis revealed that active bufadienolides could downregulate PLD1 protein levels which might promote anti-prostate cancer effect. CONCLUSIONS: All these findings support that bufadienolides might induce lipid metabolic remodeling by regulating long-chain lipids synthesis and phospholipid hydrolysis to achieve an anti-prostate cancer effect, and PLD1 would probably be the key protein.

Food phenolics stimulate adipocyte browning via regulating gut microecology.

Fat browning has piqued the interest of researchers as a potential target for treating obesity and related metabolic disorders. Recruitment of brown adipocytes leads to enhanced energy dissipation and reduced adiposity, thus facilitating the maintenance of metabolic homeostasis. Evidence is increasing to support the crucial roles of polyphenols and gut microecology in turning fat "brown". However, it is not clear whether the intestinal microecology is involved in polyphenol-mediated regulation of adipose browning, so this concept is worthy of exploration. In this review, we summarize the current knowledge, mostly from studies with murine models, supporting the concept that the effects of food phenolics on brown fat activation and white fat browning can be attributed to their regulatory actions on gut microecology, including microbial community profile, gut metabolites, and gut-derived hormones. Furthermore, the potential underlying pathways involved are also discussed. Basically, understanding gut microecology paves the way to determine the underlying roles and mechanisms of food phenolics in adipose browning.

Alkaloids from lotus (Nelumbo nucifera): recent advances in biosynthesis, pharmacokinetics, bioactivity, safety, and industrial applications.

Different parts of lotus (Nelumbo nucifera Gaertn.) including the seeds, rhizomes, leaves, and flowers, are used for medicinal purposes with health promoting and illness preventing benefits. The presence of active chemicals such as alkaloids, phenolic acids, flavonoids, and terpenoids (particularly alkaloids) may account for this plant's pharmacological effects. In this review, we provide a comprehensive overview and summarize up-to-date research on the biosynthesis, pharmacokinetics, and bioactivity of lotus alkaloids as well as their safety. Moreover, the potential uses of lotus alkaloids in the food, pharmaceutical, and cosmetic sectors are explored. Current evidence shows that alkaloids, mainly consisting of aporphines, 1-benzylisoquinolines, and bisbenzylisoquinolines, are present in different parts of lotus. The bioavailability of these alkaloids is relatively low in vivo but can be enhanced by technological modification using nanoliposomes, liposomes, microcapsules, and emulsions. Available data highlights their therapeutic and preventive effects on obesity, diabetes, neurodegeneration, cancer, cardiovascular disease, etc. Additionally, industrial applications of lotus alkaloids include their use as food, medical, and cosmetic ingredients in tea, other beverages, and healthcare products; as lipid-lowering, anticancer, and antipsychotic drugs; and in facial masks, toothpastes, and shower gels. However, their clinical efficacy and safety remains unclear; hence, larger and longer human trials are needed to achieve their safe and effective use with minimal side effects.

Global Impacts of a Bilateral Trade Policy on Ballast Water-Mediated Species Spread Risk: A Case Study of Sino-US Trade.

A trade policy could generate both economic and environmental impacts. This work is focused on the impacts of a bilateral trade policy on ballast water-mediated nonindigenous species (NIS) spread risk. Taking the hypothetical Sino-US trade restriction as an example, we integrate a computable general equilibrium model and a higher-order NIS spread risk assessment model to examine the impacts of bilateral trade policy on both the economy and NIS spread risks. We have two important findings. First, the Sino-US trade restriction would cause decreases in NIS spread risks to China and the US, as well as to three quarters of worldwide countries/regions. However, the rest one fourth would experience increased NIS spread risks. Second, the relationship between changes in exports and changes in NIS spread risks might not be directly proportional. This is observed with 46% of countries and regions that would see their exports increase but their NIS spread risks drop, with positive impacts on both their economies and environment under the Sino-US trade restriction. These results reveal both broader global impacts as well as the decoupled economic and ecological impacts of a bilateral trade policy. These broader impacts demonstrate the necessity for national governments, which are parties to bilateral agreements to give due consideration to the economic and environmental impacts on countries and regions outside of the agreement.

Prognostic potential of MNX1-AS1 in chemotherapy of colorectal carcinoma.

To clarify the role of MNX1-AS1 in 5-FU resistance of Colorectal carcinoma (CRC). Relative levels of MNX1-AS1 in CRC and paracancerous tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Recruited CRC patients were treated by 5-FU-based FOLFOX chemotherapy, and they were divided to effective group and non-effective group according to the therapeutic efficacy, followed by comparison of their differences in clinical indicators. Influences of MNX1-AS1 on clinical features of CRC were analyzed. In addition, in vitro level of MNX1-AS1 in 5-FU-resistant HCT-8 cells and their parental cells was detected. After knockdown of MNX1-AS1 in HCT-8/5-FU cells, viability change was evaluated by cell counting kit-8 (CCK-8) assay. At last, regulatory effects of MNX1-AS1 on expression levels of ABC family genes were detected. MNX1-AS1 was upregulated in CRC tissues than paracancerous ones, and its level was higher in 5-FU-resistant CRC cases in comparison to 5-FU-sensitive cases. MNX1-AS1 level was linked to tumor size, tumor differentiation, depth of invasion, TNM staging and lymphatic metastasis in CRC. Notably, TNM staging, depth of invasion and lymphatic metastasis could affect the efficacy of FOLFOX chemotherapy in CRC patients. Knockdown of MNX1-AS1 reduced viability in HCT-8/5-FU cells, and downregulated ABCA1, ABCB1, ABCC1, ABCG1 and ABCG2. MNX1-AS1 triggers 5-FU resistance in CRC cells. Knockdown of MNXK1-AS1 is conductive to the well response to FOLFOX chemotherapy in CRC patients.

The role of gut microbiota and metabolites in regulating the immune response in drug-induced enteritis.

Drug-induced enteritis is an inflammatory disease changing in the morphology and function of the intestine as a result of medicine damage. With the increase in drug abuse in recent years, the incidence of drug-associated enteritis accordingly rises and becomes an important disease affecting the health and life quality of patients. Hence, elucidating the pathogenesis of drug-induced enteritis and finding cost-effective diagnostic and therapeutic tools have become current research focuses. The gut microbiota and metabolites regulate the immune response, playing a key role in the maintenance of homeostasis in the intestine. Numerous studies have found that many medicines can induce intestinal flora disorders, which are closely related to the development of drug-induced enteritis. Therefore, this paper analyses the role of gut microbiota and metabolites in regulating the immune response, and provides basic research direction and clinical reference strategies for drug-induced enteritis, taking into account the existing applications and perspectives.

Genome-wide association study reveals candidate genes for pollution excreta traits in pigs.

Excreta traits comprise a very important characteristic in breeding that have been neglected for a long time. With the growth of intensive pig farming, plenty of environment problems have been raised, and people have begun to pay attention to pig excreta behaviors from genetics and breeding perspectives. However, the genetic architecture of excreta traits remains unclear. To investigate the genetic architecture of excreta traits in pigs, eight excreta traits and feed conversion ratio (FCR) were analyzed in this study. We performed genome-wide association studies (GWASs) on 213 Yorkshire pigs and estimated genetic parameters for a total number of 290 pigs, comprising 213 Yorkshire, 52 Landrace and 25 Duroc. After analysis, eight and 22 genome-wide significant SNPs were detected for FCR and the eight excreta traits in single-trait GWASs separately, and 18 were detected in a multi-trait meta-analysis for excreta traits, six of which were detected in both the single-trait and the multi-trait GWAS. Eighty, 182 and 133 genes were detected within 1 Mb of the genome-wide significant SNPs for FCR, excreta traits and multi-trait meta-analysis, respectively. Five candidate genes (BCKDC, DBT, ANKRD7, SHPRH and HCRT) with biochemical and physiological effects relevant to feed efficiency and excreta traits might be interesting markers for future breeding. Meanwhile, functional enrichment analysis indicates that most of the significant pathways are associated with the glutathione catabolic process, DNA topological change and replication fork protection complex. This study reveals the architecture of excreta traits in commercial pigs and offers an opportunity for decreasing the pollution from excreta using genomic selection in pigs.

Global, regional and national burden of male infertility in 204 countries and territories between 1990 and 2019: an analysis of global burden of disease study.

BACKGROUND: Many countries and regions have experienced male fertility problems due to various influencing factors, especially in less developed countries. Unlike female infertility, male infertility receives insufficient attention. Understanding the changing patterns of male infertility in the world, different regions and different countries is crucial for assessing the global male fertility and reproductive health. METHODS: We obtained data on prevalence, years of life lived with disability (YLD), age-standardized rates of prevalence (ASPR) and age-standardized YLD rate (ASYR) from the Global Burden of Disease Study 2019. We analyzed the burden of male infertility at all levels, including global, regional, national, age stratification and Socio-demographic Index (SDI). RESULTS: In 2019, the global prevalence of male infertility was estimated to be 56,530.4 thousand (95% UI: 31,861.5-90,211.7), reflecting a substantial 76.9% increase since 1990. Furthermore, the global ASPR stood at 1,402.98 (95% UI: 792.24-2,242.45) per 100,000 population in 2019, representing a 19% increase compared to 1990. The regions with the highest ASPR and ASYR for male infertility in 2019 were Western Sub-Saharan Africa, Eastern Europe, and East Asia. Notably, the prevalence and YLD related to male infertility peaked in the 30-34 year age group worldwide. Additionally, the burden of male infertility in the High-middle SDI and Middle SDI regions exceeded the global average in terms of both ASPR and ASYR. CONCLUSION: The global burden of male infertility has exhibited a steady increase from 1990 to 2019, as evidenced by the rising trends in ASPR and ASYR, particularly in the High-middle and Middle SDI regions. Notably, the burden of male infertility in these regions far exceeds the global average. Additionally, since 2010, there has been a notable upward trend in the burden of male infertility in Low and Middle-low SDI regions. Given these findings, it is imperative to prioritize efforts aimed at improving male fertility and reproductive health.