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The micronutrient zinc plays an essential role in the physiological and metabolic processes in plants; however, it becomes very toxic when present in elevated amounts. To evaluate the correlation of metal tolerance proteins (MTP) with Zn accumulation and distribution in Malus halliana seedlings under zinc toxicity stress, seedlings with 8 true leaves were exposed to different Zn concentrations (4, 25, 50, 100 μmol·L−1) in a hydroponic culture system. We found that excessive Zn stress leads to a decrease in plant growth indexes and the accumulation and distribution of Zn in Malus halliana. With increasing levels of Zn stress, the Zn concentration in roots was significantly higher than in stems and leaves. At 100 μmol·L−1 Zn, the Zn concentration in roots, stems and leaves increased by 45.88, 26.51 and 25.43-fold when compare to CK, respectively. The increase of bioaccumulation factor (BAF) and the decrease of translocation factor (TF) all indicated that Zn was accumulated in the roots. Correlation and hierarchical clustering analysis found that the expression of MTP genes is closely associated with Zn concentrations. The MTP2, MTP11 and MTPC2-like genes were significantly negatively correlated with Zn concentration in roots and were resistant to excessive Zn concentration and sequestration. The expression of MTP1 had organ-specificity that was significantly higher in stems and leaves than that in roots. The expression of MTPC4-like was significantly positively correlated with Zn concentration under the treatment of 4 μmol·L−1 Zn, but the correlation decreased under the high concentration of Zn stress, which indicated that the expression of MTP gene was affected by Zn concentration. [ABSTRACT FROM AUTHOR]

The introduction of excess PbI2 into CH3NH3PbI3 precursors has been reported to boost the efficiency of CH3NH3PbI3 solar cell. It was assumed that the excess PbI2 helped to reduce the defect density in CH3NH3PbI3 solar cell. In this work, by adding non-equimolar PbI2 into CH3NH3PbI3 precursor solution, PbI2-rich CH3NH3PbI3 solar cells have been fabricated. The efficiency of CH3NH3PbI3 solar cell was significantly improved from 14.14% to 16.80%. Results obtained from scanning electron microscopy (SEM) and X-ray diffraction (XRD) indicate that the excess PbI2 does not affect the morphological and crystal properties of CH3NH3PbI3 thin film. Based on time-resolved photoluminescence (TRPL) measurement, it was found that the carrier lifetime of PbI2-rich perovskite thin film was significantly increased. Lower defect density was observed in PbI2-rich CH3NH3PbI3 solar cell by admittance spectroscopy (AS) characterization, indicating PbI2 can suppress the formation of defects in CH3NH3PbI3 solar cells. [ABSTRACT FROM AUTHOR]

Salt tolerance genes constitute an important class of loci in plant genomes. Little is known about the extent to which natural selection in saline environments has acted upon these loci, and what types of nucleotide diversity such selection has given rise to. Here, we surveyed genetic diversity in three types of Na+/H+ antiporter gene ( SOS, NhaD, and NHX, belonging to the cation/proton antiporter 1 family), which have well -characterized essential roles in plant salt tolerance. Ten Na+/H+ antiporter genes and 16 neutral loci randomly selected as controls were sequenced from 17 accessions of two closely related members of the genus Populus, Populus euphratica and Populus pruinosa, section Turanga, which are native to northwest China. The results show that salt tolerance genes are common targets of natural selection in P. euphratica and P. pruinosa. Moreover, the patterns of nucleotide variation across the three types of Na+/H+ antiporter gene are distinctly different in these two closely related Populus species, and gene flow from P. pruinosa to P. euphratica is highly restricted. Our results suggest that natural selection played an important role in shaping the current distinct patterns of Na+/H+ antiporter genes, resulting in adaptive evolution in P. euphratica and P. pruinosa. [ABSTRACT FROM AUTHOR]

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• A novel radio frequency cool plasma technology, using Ar/O 2 mixed, was applied to surface modification of In 2 O 3 electrospun nanofibers to form an oxide-rich structure. • Adsorption energy and electron transfer of acetone on In 2 O 3 after modification was 1217 eV and 0.072 |e| according to the calculation results based on DFT, respectively, higher than that of before plasma modification, which are the vital reason to improve the acetone sensing properties of In 2 O 3 sensor. • After modification of Ar/O 2 mixed plasma, the doping state introduced by Ar/O 2 mixed plasma change the electronic state of In 2 O 3. The more adsorbed oxygen occupies the oxygen defects, adsorption ability of In 2 O 3 gas sensor to acetone is increased greatly. Surface adsorbed oxygen plays a crucial role in the redox reactions of semiconductor gas sensors. A novel, radio frequency plasma modification method, using mixed Ar/O 2 , was applied to surface treatment of In 2 O 3 electrospun nanofibers to form an oxide-rich structure. Acetone adsorption behavior on the In 2 O 3 (110) surface was investigated using density functional theory (DFT). With the injection of high-energy Ar/O 2 plasma, an unoccupied electronic state was formed in the valence band electronic structure of In 2 O 3. The adsorption energy of acetone on In 2 O 3 after modification was 0.136 eV higher than before plasma modification. The adsorption ability of acetone was greatly improved after modification of Ar/O 2 plasma. In 2 O 3 sensors were fabricated before and after plasma modification, and the acetone sensing performances were measured. Gas sensing measurement showed that the Ar/O 2 mixed plasma modification caused a unique improvement in the acetone sensing performance of the In 2 O 3 sensors. [ABSTRACT FROM AUTHOR]

MicroRNAs are small non-coding RNA regulatory molecules that play an important role in the development and function of immune cells. MicroRNA-26a (miR-26a) exhibits anti-inflammatory immune effects on immune cells. However, the exact mechanism by which miR-26a plays an anti-inflammatory role remains unclear. Here, we report that miR-26a reduces inflammatory response via inhibition of prostaglandin E2 (PGE2) production by targeting cyclooxygenase-2 (COX-2). We found that miR-26a was downregulated in vitro and in vivo. The miR-26a mimic significantly decreased COX-2 protein levels, further inhibiting pro-inflammatory cytokine production in LPS-stimulated macrophages. We predicted that miR-26a could potentially target COX-2 in LPS-stimulated macrophages. Computational algorithms showed that the 3′-UTR of COX-2 mRNA contains a binding site for miR-26a. This putative targeting relationship between miR-26a and COX-2 was further confirmed by a dual-reporter gene assay. The anti-inflammatory effects of the miR-26a mimic were diminished by PGE2 supplementation. Importantly, miR-26a mimics protected mice from lethal endotoxic shock and attenuated pro-inflammatory cytokine production. Collectively, these results suggest that miR-26a may function as a novel feedback negative regulator of the hyperinflammatory response and as a drug target for the progression of inflammation. [ABSTRACT FROM AUTHOR]

We sought to explore the role of postanthesis carbon and nitrogen (C-N) metabolism of hybrid rice in increasing yield and nitrogen utilization efficiency (NUE). We used the 13C and 15N dual-isotope tracer method and physiological/biochemical analysis and established different irrigation and nitrogen fertilization (W-N) regimes to investigate the relationship of C-N metabolism characteristics, yield, and NUE. The results showed that W-N regimes had significant effects on postanthesis absorption and translocation of N and photosynthate, yield and NUE. Aerobic irrigation combined with the N fertilization regime 30% base, 30% tillering, 40% booting was the best W-N coupling regime for rice yield and NUE increase. The regime enhanced flag leaf photosynthesis rate and the activities of ribulose 1,5-diphosphate carboxylase/oxygenase (RuBPCase), glutamine synthetase (GS), and other key enzymes of C-N metabolism, and improved the total accumulations of photoassimilates (0.97–21.57 mg 13C plant−1) and N (1.55–23.36 mg 15N plant−1), respectively. Correlation analysis showed that, under the W-N interaction, C-N metabolism enzymes promoted the positive synergistic effect between 13C and 15N accumulation in panicles (r = 0.825). In addition, the change in C/N ratio can be used as an indicator of the simultaneous improvement in yield and NUE in hybrid rice. [ABSTRACT FROM AUTHOR]

Recent studies had explored that gut microbiota was associated with personality traits through the gut-brain axis. Nevertheless, the fundamental causality remained obscure. Mendelian randomization (MR) was used to investigate the causal relationship between gut microbiota, metabolites and neuroticism-related traits. Summary data-based Mendelian randomization (SMR) was utilized to identify genes associated pleiotropically with microbial taxa. MR analyses identified reliable causal evidence of 20 bacterial taxa related to neuroticism and its worry or depressed affect sub-cluster. A higher relative abundance of the Ruminococcus gauvreauii genus was associated with a higher risk of neuroticism [odds ratio (OR) = 1.04, 95% CI: 1.02–1.06, P = 2.85 × 10–3], depressed affect [OR = 1.04, 95% CI: 1.02–1.06, P = 5.50 × 10–3] and worry (OR = 1.04, 95% CI: 1.02–1.06, P = 7.81 × 10–4), respectively. We identified the probes tagging CPSF1, that showed pleiotropic association with Ruminococcus gauvreauii in brain or colon tissues. Finally, we provided evidence that Ruminococcus gauvreauii present causal association with the neurotransmitter such as glutamine and glutamate. This study implied a causal relationship between the gut microbiome composition, metabolites and neuroticism, thus providing novel insights into the gut microbiota-mediated development mechanism of neuroticism. • Twenty bacterial texas causally associated with the risk of neuroticism and its sub-clusters. • Abundance of the Ruminococcus gauvreauii casually associated with the risk of neuroticism. • CPSF1 showed pleiotropic association with Ruminococcus gauvreauii in brain or colon tissues. • Ruminococcus gauvreauii present causal association with the neurotransmitter such as glutamine and glutamate. • Ruminococcus gauvreauii-CPSF1-glutamine/glutamate axis in neuroticism. [ABSTRACT FROM AUTHOR]

Objective:To explore external validity of randomized controlled trials (RCTs) of hypertension within China from the view of sample representation. Methods:Comprehensive literature searches were performed in Medline, Embase, Cochrane Central Register of Controlled Trials (CCTR) et al and advanced search strategies were used to locate hypertension RCTs as well as observational studies conducted in China during 1996 to 2009 synchronously. The risk of bias in RCTs and observational studies was assessed by two modified scales respectively, and then both types of studies with 3 or more grading scores were included for the purpose of evaluating of external validity. Following that the study characteristics relative to sample representation were extracted from RCTs and observational studies synchronously, and the later were taken as external references for validating sample representation of RCTs. Results:226 hypertension RCTs and 21 observational studies were included for final analysis. Comparing samples with observational studies, the mean age of samples within RCTs was 54.46 years, significantly lower than that of observational studies (66.35 years) (P=0.002). The average disease course in patients of RCTs was 3.89 years and grade III hypertensive patients accounted for 17%; both were lower than that of the observational studies (12.96 years, P<0.001; 34%, P=0.026 respectively). In addition, the proportions of patients with complications due to heart failure, stroke, diabetes, or coronary heart disease in RCTs were 8%, 5%, 12% and 11% correspondingly, all of which were significantly less than that of observational studies (11%, 18%, 17% and 29%). Conclusion:Sample characteristics within hypertension RCTs were significantly different from those in observational studies. The samples in most RCTs were under-represented. It’s feasible to take samples of observational studies as a mirror of the actual composition of hypertension patients in the real world, if the reporting of observational studies is abundant and available. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that the brain is highly dynamic; thus, investigation of brain dynamics especially in brain connectivity would provide crucial information that stationary functional connectivity could miss. This study investigated temporal expressions of spatial modes within the default mode network (DMN), salience network (SN) and cognitive control network (CCN) using a reliable data-driven co-activation pattern (CAP) analysis in two independent data sets. We found enhanced CAP-to-CAP transitions of the SN in patients with MDD. Results suggested enhanced flexibility of this network in the patients. By contrast, we also found reduced spatial consistency and persistence of the DMN in the patients, indicating reduced variability and stability in individuals with MDD. In addition, the patients were characterized by prominent activation of mPFC. Moreover, further correlation analysis revealed that persistence and transitions of RCCN were associated with the severity of depression. Our findings suggest that functional connectivity in the patients may not be simply attenuated or potentiated, but just alternating faster or slower among more complex patterns. The aberrant temporal–spatial complexity of intrinsic fluctuations reflects functional diaschisis of resting-state networks as characteristic of patients with MDD. [ABSTRACT FROM AUTHOR]

Breast cancer stem cells (BCSCs) are the main cause of breast cancer recurrence and metastasis. While the ubiquitin-proteasome system contributes to the regulation of BCSC stemness, the underlying mechanisms remain unclear. Here, we identified ubiquitin-conjugating enzyme E2T (UBE2T) as a pivotal ubiquitin enzyme regulating BCSC stemness through systemic screening assays, including single-cell RNA sequencing (scRNA-seq) and stemness-index analysis. We found that patients with high UBE2T expression exhibited worse prognosis than those with low expression (10-year PFS: 55.95 % vs. 85.08 %), which are consistent across various subtypes of breast cancers. Genetic ablation of UBE2T suppresses BCSC stemness and tumor progression in organoids and spontaneous MMTV-PyMT mice, dependent on the transcriptional inactivation of pluripotency genes SOX2 and NANOG. Mechanically, UBE2T collaborates with the E3 ligase TRIM25 to perform K48-linked polyubiquitination and degradation of CBX6 at K214, which deficiency helps to promote the transcription of SOX2 and NANOG and enhances BCSC stemness. The pharmacological inhibitor of UBE2T significantly reduced the expression of NANOG and SOX2, suppressed tumor progression, and demonstrated synergistic effects when combined with chemotherapeutics, but not with other treatments. Collectively, our study revealed that the UBE2T-TRIM25-CBX6 axis can regulate BCSC stemness and offers a potentially therapeutic strategy to combat breast cancer in a clinical translation setting. • UBE2T facilitates tumorigenesis and the progression of breast cancer. • The UBE2T/TRIM25/CBX6 axis drives SOX2 and NANOG-mediated BCSC stemness. • Targeting UBE2T inhibits BCSC stemness and breast cancer progression. [ABSTRACT FROM AUTHOR]

The recommendation system is fundamental technology of the internet industry intended to solve the information overload problem in the big data era. Top-k recommendation is an important task in this field. It generally functions through the comparison of positive pairs and negative pairs based on Bayesian personalized ranking (BPR) loss. We find that the contrastive loss (CL) function used in contrastive learning is well-suited for top-k recommendation. However, there are two problems in the existing loss functions. First, all samples are treated the same, and hard samples are not considered. Second, all nonpositive samples are considered negative samples, which ignores the fact that they are unlabelled data containing items that users may like. Moreover, in our experiments, we find that when items are sorted by their similarities to the user, many negative items (or samples) appear before the positive items. We regard these negative items as hard samples and those at the top as potentially positive samples due to their high level of similarities with users. Therefore, we propose a ranking-based contrastive loss (RCL) function to exploit both hard samples and potentially positive samples. Experimental results demonstrate the effectiveness, broad applicability, and high training efficiency of the proposed RCL function. The code and data are available at https://github.com/haotangxjtu/RCL. [ABSTRACT FROM AUTHOR]

Blotched snakehead (Channa maculata) is one of the most important freshwater fish in China. Genome editing is of great potential in generating new snakehead strains with valuable economic traits without integration of exogenous genes. Myostatin (Mstn) inhibits the development and growth of skeletal muscle in vertebrates, including teleosts. Mstn mutations induced by genome editing can stimulate muscle growth and development, therefore Mstn is an appropriate candidate to breed the fast-growing snakehead strain. For this study, one orthologous Mstn gene was characterized in C. maculata , designated as CmMstn , which possessed the relatively conserved gene and protein structure. CmMstn had the highest expression level and sexual dimorphism in muscles. Two CRISPR/Cas9 target sites were designed to generate knockout mutants within the mature mRNA sequence of CmMstn located in Exon I and Exon II. 1 nL mixture solution of 200 pg gRNA and 300 pg Cas9 protein was directly microinjected into each snakehead embryonic yolk at 1⁓4 cell stage. Mstn was efficiently edited by CRISPR/Cas9 system in shakehead, and all designed gRNAs effectively worked at their target sites with high mutagenesis efficiencies, from 40.0% to 53.3%. The majority of mutations were frame-shift and resulted in premature termination of transcription and disruption of the molecular function of Cm Mstn protein. Furthermore, we obtained four founders (F0) of snakehead with the mutated Mstn gene in their primordial germ cells, and nineteen F1 offspring of the F0 mutants mated with wild-type individuals were displayed to carry Mstn null alleles. It is the first application of genome editing technology in blotched snakehead, and CRISPR/Cas9 system successfully edit the primordial germ cells. Our findings will accelerate our understanding of the role of Mstn gene in snakehead growth, and speed up the cultivation of the fast-growing snakehead strain. • One orthologous Mstn gene was characterized in Channa maculata (CmMstn). • CmMstn had the highest expression level and sexual dimorphism in muscles. • Genome editing of the Mstn by CRISPR/Cas9 system was successfully accomplished in blotched snakehead. • Heritable targeted inactivation of Mstn in F1 knockout blotched snakehead were generated. [ABSTRACT FROM AUTHOR]

Mangroves, as blue carbon reservoirs, provide a unique habitat for supporting a variety of microorganisms. Among these, bacteria play crucial roles in the biogeochemical processes of mangrove sediments. However, little is known about their community composition, spatial distribution patterns, and environmental driving factors, particularly across the large geographical scales of mangrove wetlands. In this study, the composition and spatial distribution of the bacterial community structure and its response to fifteen physicochemical parameters (including temperature, pH, salinity, moisture, clay, silt, sand, organic carbon (OC), total nitrogen (TN), total phosphorus (TP), inorganic phosphorus (IP), organic phosphorus (OP), δ 13 C, δ 15 N, and carbon/nitrogen ratio (C/N ratio)) were characterized in 32 sampling locations of six different mangrove habitats from Guangxi, China, applying 16S rRNA gene high-throughput sequencing technology and correlation analysis. Our results indicated that the spatial distribution patterns in bacterial communities were significantly different among the six different mangrove sites, as evidenced by NMDS (non-metric multidimensional scaling), ANOSIM (analysis of similarity), and LDA (linear discriminant analysis) analysis. Composition analysis of bacterial communities showed that overall, Chloroflexi (8.3-31.6%), Proteobacteria (13.6-30.1%), Bacteroidota (5.0-24.6%), and Desulfobacterota (3.8-24.0%) were the most abundant bacterial phyla in the mangrove surface sediments. Redundancy analysis (RDA) further highlighted that salinity, δ 13 C, temperature, δ 15 N, and silt were the most critical environmental variables influencing the composition of bacterial communities across the whole mangrove samples. Notably, Chloroflexi, one of the most abundant bacterial phyla in the mangrove wetlands, displayed a significantly positive correlation with OC and a negative correlation with δ 13 C, suggesting its essential role in the degradation of terrestrial-derived organic carbon. These findings support the current understanding of the roles of the bacterial communities and their interactions with environmental factors in diverse mangrove ecosystems.

The 5-fluorouracil (5-FU)-based chemotherapy regimen is a primary strategy for treating pancreatic cancer (PC). However, challenges related to 5-FU resistance persist. Investigating the mechanisms of 5-FU resistance and identifying a clinically viable therapeutic strategy are crucial for improving the prognosis of PC. Here, through clinical samples analysis, we found that the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the rate-limiting enzyme in mevalonate metabolism, is negatively correlated with the efficacy of 5-FU treatment. There is a significant correlation between HMGCR and the pyroptosis marker gasdermin D (GSDMD), and the HMGCR inhibitor simvastatin can significantly inhibit the activation of pyroptosis signaling. The exogenous addition of geranylgeranyl pyrophosphate (GGPP), a key metabolite of the mevalonate pathway, can significantly reduce sensitivity to 5-FU, and simvastatin combined with 5-FU demonstrates a strong synergistic effect. Furthermore, in organoid models and genetically engineered mice with spontaneous PC, the combination of simvastatin and 5-FU significantly inhibits tumor growth. In conclusion, our study reveals the critical role of the mevalonate pathway in 5-FU resistance and proposes a clinically feasible combination therapy strategy., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no competing interests. Ethical approval: This research was conducted in accordance with the ethical standards and approved by the Human Research Ethics Committee of Lanzhou University Second Hospital (Permit No. 2023A-173). The animal research was reviewed and approved by the Animal Experiment Ethics Committee of Lanzhou University Second Hospital (Permit No. D2023–M2). Consent for Publication: Not applicable., (© 2024. The Author(s).)

Purpose: To investigate psychiatric nurses' emotional intelligence and its effect on care behavior, while also examining the mediating effect of compassion fatigue and perception of management., Method: This cross-sectional study was conducted in several specialized psychiatric hospitals with 360 psychiatric nurses. Self-report surveys were administered, which included the Caring Factor Survey-Caring of Manager, Caring Behaviors Inventory, Compassion Fatigue Short Scale, and Wong Law Emotional Intelligence Scale. Data were analyzed using descriptive, correlation, and path analyses., Results: Mean score for care behavior was 4.78 ( SD = 0.83), which was at a moderate level. Compassion fatigue exhibited negative correlations with other variables. Results of mediation effect analysis showed that emotional intelligence directly predicted care behavior ( p < 0.001). Emotional intelligence also indirectly affected care behavior through the mediating roles of perception of management and compassion fatigue, and affected care behavior through the chain mediation effect of perception of management and compassion fatigue., Conclusion: Nurse managers should pay attention to the influence of emotional intelligence on care behavior and improve care behavior by strengthening leadership and alleviating compassion fatigue. [ Journal of Psychiatric Nursing and Mental Health Services, xx (xx), xx-xx.].

Objective: To evaluate the effectiveness of the YEARS algorithm for excluding pulmonary embolism (PE) in hospitalized women after cesarean section., Methods: This retrospective study included postpartum women who gave birth by cesarean section and received computed tomography pulmonary angiography (CTPA) because of suspected PE in the obstetric department between 2015 and 2021. We used the YEARS algorithm in these women retrospectively and assessed its performance to evaluate whether the algorithm could be reliably applied in such cases., Results: In all, 225 women were included in the study, of whom 29 (12.9%) women were positive for PE according to the results of CTPA. Upon retrospective application of the YEARS algorithm, 188 (83.6%) women had no YEARS items, while 37 (16.4%) women had YEARS items. Combining the results with D-dimer levels revealed that only 12 (5.3%) women did not need to undergo CTPA, and none showed PE., Conclusion: The YEARS algorithm could be applied to exclude PE in hospitalized women in the early post-cesarean period. However, the specificity of the YEARS algorithm was very low, and the D-dimer cut-off for ruling out PE in women after early cesarean section should be further studied and optimized., (© 2024 International Federation of Gynecology and Obstetrics.)

Background: Blotched snakehead (Channa maculata) displays significant sexual dimorphism, with males exhibiting faster growth rates and larger body sizes compared to females. The cultivation of the all-male population of snakeheads holds substantial economic and ecological value. Nonetheless, the intricate processes governing the development of bipotential gonads into either testis or ovary in C. maculata remain inadequately elucidated. Therefore, it is necessary to determine the critical time window of sex differentiation in C. maculata, providing a theoretical basis for sex control in production practices., Methods: The body length and weight of male and female C. maculata were measured at different developmental stages to reveal when sexual dimorphism in growth initially appears. Histological observations and spatiotemporal comparative transcriptome analyses were performed on ovaries and testes across various developmental stages to determine the crucial time windows for sex differentiation in each sex and the sex-related genes. Additionally, qPCR and MG2C were utilized to validate and locate sex-related genes, and levels of E 2 and T were quantified to understand sex steroid synthesis., Results: Sexual dimorphism in growth became evident starting from 90 dpf. Histological observations revealed that morphological sex differentiation in females and males occurred between 20 and 25 dpf or earlier and 30-35 dpf or earlier, respectively, corresponding to the appearance of the ovarian cavity or efferent duct anlage. Transcriptome analyses revealed divergent gene expression patterns in testes and ovaries after 30 dpf. The periods of 40-60 dpf and 60-90 dpf marked the initiation of molecular sex differentiation in females and males, respectively. Male-biased genes (Sox11a, Dmrt1, Amh, Amhr2, Gsdf, Ar, Cyp17a2) likely play crucial roles in male sex differentiation and spermatogenesis, while female-biased genes (Foxl2, Cyp19a1a, Bmp15, Figla, Er) could be pivotal in ovarian differentiation and development. Numerous biological pathways linked to sex differentiation and gametogenesis were also identified. Additionally, E 2 and T exhibited sexual dimorphism during sex differentiation and gonadal development. Based on these results, it is hypothesized that in C. maculata, the potential male sex differentiation pathway, Sox11a-Dmrt1-Sox9b, activates downstream sex-related genes (Amh, Amhr2, Gsdf, Ar, Cyp17a2) for testicular development, while the antagonistic pathway, Foxl2/Cyp19a1a, activates downstream sex-related genes (Bmp15, Figla, Er) for ovarian development., Conclusions: This study provides a comprehensive overview of gonadal dynamic changes during sex differentiation and gametogenesis in C. maculata, establishing a scientific foundation for sex control in this species., (© 2024. The Author(s).)

Soil salinization is one of the major environmental factors that restrict plant growth and development. Zeaxanthin epoxidase (ZEP) functions in ABA biosynthesis and the xanthophyll cycle and has a vital role in plant responses to various environmental stresses. It was found by quantitative real-time PCR (qRT-PCR) that MhZEP responded to saline-alkali stress and showed the highest expression at 48 h of saline-alkali stress, which was 14.53-fold of 0 h. The MhZEP gene was cloned from the apple rootstock begonia ( Malus halliana Koehne) and its protein physicochemical properties were analyzed. Subsequently, the functional characterization of MhZEP (ID: 103403091) was further investigated in Arabidopsis thaliana . The MhZEP contained a complete open reading frame with a length of 1998 bp, and encoded 665 amino acids with an isoelectric point of 7.18. Phylogenetic tree analysis showed that MhZEP was the most homologous and closely related to Glycine max . Compared with wild-type, transgenic plants grew better under saline-alkali stress and the MhZEP -OE line showed higher chlorophyll content, carotenoid content, enzyme activities (POD, SOD, CAT and APX) and K + content, whereas they had lower chlorosis and Na + content than the wild type (WT), which indicated that they had strong resistance to stress. The expression levels of saline-alkali stress-related genes in A. thaliana MhZEP -OE were examined by qRT-PCR, and it was found that the MhZEP improved the tolerance of A. thaliana to saline-alkali stress tolerance by regulating the expression of carotenoid synthesis genes ( MhPSY , MhZDS , MhLYCB and MhVDE ) and ABA biosynthesis genes ( MhNCED5 , MhABI1 and MhCYP707A2 ). And the potassium-sodium ratio in the cytoplasm was increased to maintain ionic homeostasis by modulating the expression of Na + transporter genes ( MhCHX15 and MhSOS1 ) and K + transporter genes ( MhHKT1;1 , MhNHX1 and MhSKOR1 ). Moreover, the expression of H + -ATPase genes ( MhAHA2 and MhAHA8 ) was increased to reduce the oxidative damage caused by saline-alkali stress. In summary, MhZEP acted as an essential role in plant resistance to saline-alkali stress, which lays the foundation for further studies on its function in apple., Competing Interests: Conflict of interestThese authors declare that they have no conflict of interest., (© Prof. H.S. Srivastava Foundation for Science and Society 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Numerous local herbal extract species have been investigated as potential medicinal ingredients due to their promising anti-cancer properties. However, the primary constraint of the class of plant flavonoids lies in their low solubility and limited membrane permeability, leading to chemical instability and restricted bioavailability that impede biomedical applications. In this study, we have developed an ideal nanozyme-Galazyme, comprising galangin-loaded copper Nanozyme coated by DSPE-PEG, which amplifies oxidative stress to induce apoptosis via the regulation of reactive oxygen species (ROS) generation and mitogen-activated protein kinase (MAPK) activation. Galazyme exhibited significant peroxidase mimetic activity, demonstrating its potential to generate ROS and elevate oxidative stress. Upon uptake by HepG-2 cells, Galazyme efficiently converts excess hydrogen peroxide (H2O2) into highly reactive •OH radicals and upregulates MAPK expression, leading to the activation of Bax and Caspase 3, thereby promoting irreversible tumor cell apoptosis. Both in vitro and in vivo results demonstrate that Galazyme inhibits tumor cell growth and induces apoptosis by generating ample ROS and activating the MAPK pathway. Our study offers novel evidence supporting the enhancement of Galazyme-induced apoptosis through the upregulation of Bax and Caspase 3, along with the elucidation of the interaction between MAPK and apoptosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Wu, Wang, Li, Liang, Wang, Liu, Feng, Mao, Zhu and Li.)

Digestive system neoplasms are highly heterogeneous and exhibit complex resistance mechanisms that render anti-programmed cell death protein (PD) therapies poorly effective. The tumor microenvironment (TME) plays a pivotal role in tumor development, apart from supplying energy for tumor proliferation and impeding the body's anti-tumor immune response, the TME actively facilitates tumor progression and immune escape via diverse pathways, which include the modulation of heritable gene expression alterations and the intricate interplay with the gut microbiota. In this review, we aim to elucidate the mechanisms underlying drug resistance in digestive tumors, focusing on immune-mediated resistance, microbial crosstalk, metabolism, and epigenetics. We will highlight the unique characteristics of each digestive tumor and emphasize the significance of the tumor immune microenvironment (TIME). Furthermore, we will discuss the current therapeutic strategies that hold promise for combination with cancer immune normalization therapies. This review aims to provide a thorough understanding of the resistance mechanisms in digestive tumors and offer insights into potential therapeutic interventions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Tumors of the digestive system are currently one of the leading causes of cancer-related death worldwide. Despite considerable progress in tumor immunotherapy, the prognosis for most patients remains poor. In the tumor microenvironment (TME), tumor cells attain immune escape through immune editing and acquire immune tolerance. The mevalonate pathway and autophagy play important roles in cancer biology, antitumor immunity, and regulation of the TME. In addition, there is metabolic crosstalk between the two pathways. However, their role in promoting immune tolerance in digestive system tumors has not previously been summarized. Therefore, this review focuses on the cancer biology of the mevalonate pathway and autophagy, the regulation of the TME, metabolic crosstalk between the pathways, and the evaluation of their efficacy as targeted inhibitors in clinical tumor immunotherapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Ubiquitination is an important protein modification that regulates diverse biological processes, including CD4 + T cell differentiation and functions. However, the function of most E3 ubiquitin ligases in CD4 + T cell differentiation and CD4 + T cell-mediated pathological diseases remains unclear. In this study, we find that tripartite motif-containing motif 11 (TRIM11) specifically negatively regulates regulatory T (Treg) cell differentiation in CD4 + T cells and promotes autoimmune disease development in an AIM2-dependent manner. Mechanistically, TRIM11 interacts with absent in melanoma 2 (AIM2) and promotes the selective autophagic degradation of AIM2 by inducing AIM2 ubiquitination and binding to p62 in CD4 + T cells. AIM2 attenuates AKT and FOXO1 phosphorylation, MYC signaling, and glycolysis, thereby promoting the stability of Treg cells during experimental autoimmune encephalomyelitis (EAE). Our findings suggest that TRIM11 serves as a potential target for immunotherapeutic intervention for dysregulated immune responses that lead to autoimmunity and cancers., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)