Enhancing ion selectivity by tuning solvation abilities of covalent-organic-framework membranes.

Understanding the molecular-level mechanisms involved in transmembrane ion selectivity is essential for optimizing membrane separation performance. In this study, we reveal our observations regarding the transmembrane behavior of Li+ and Mg2+ ions as a response to the changing pore solvation abilities of the covalent-organic-framework (COF) membranes. These abilities were manipulated by adjusting the lengths of the oligoether segments attached to the pore channels. Through comparative experiments, we were able to unravel the relationships between pore solvation ability and various ion transport properties, such as partitioning, conduction, and selectivity. We also emphasize the significance of the competition between Li+ and Mg2+ with the solvating segments in modulating selectivity. We found that increasing the length of the oligoether chain facilitated ion transport; however, it was the COF membrane with oligoether chains containing two ethylene oxide units that exhibited the most pronounced discrepancy in transmembrane energy barrier between Li+ and Mg2+, resulting in the highest separation factor among all the evaluated membranes. Remarkably, under electro-driven binary-salt conditions, this specific COF membrane achieved an exceptional Li+/Mg2+ selectivity of up to 1352, making it one of the most effective membranes available for Li+/Mg2+ separation. The insights gained from this study significantly contribute to advancing our understanding of selective ion transport within confined nanospaces and provide valuable design principles for developing highly selective COF membranes.

Salicylic acid regulates two photosystem II protection pathways in tomato under chilling stress mediated by ETHYLENE INSENSITIVE 3-like proteins.

Chilling stress seriously impairs photosynthesis and activates a series of molecular responses in plants. Previous studies have shown that ETHYLENE INSENSITIVE 3 (EIN3) and EIN3-like (SlEIL) proteins mediate ethylene signaling and reduce plant tolerance to freezing in tomato (Solanum lycopersicum). However, the specific molecular mechanisms underlying an EIN3/EILs-mediated photoprotection pathway under chilling stress are unclear. Here, we discovered that salicylic acid (SA) participates in photosystem II (PSII) protection via SlEIL2 and SlEIL7. Under chilling stress, the phenylalanine ammonia-lyase gene SlPAL5 plays an important role in the production of SA, which also induces WHIRLY1 (SlWHY1) transcription. The resulting accumulation of SlWHY1 activates SlEIL7 expression under chilling stress. SlEIL7 then binds to and blocks the repression domain of the heat shock factor SlHSFB-2B, releasing its inhibition of HEAT SHOCK PROTEIN 21 (HSP21) expression to maintain PSII stability. In addition, SlWHY1 indirectly represses SlEIL2 expression, allowing the expression of l-GALACTOSE-1-PHOSPHATE PHOSPHATASE3 (SlGPP3). The ensuing higher SlGPP3 abundance promotes the accumulation of ascorbic acid (AsA), which scavenges reactive oxygen species produced upon chilling stress and thus protects PSII. Our study demonstrates that SlEIL2 and SlEIL7 protect PSII under chilling stress via two different SA response mechanisms: one involving the antioxidant AsA and the other involving the photoprotective chaperone protein HSP21.

Enhancing Sustainable Energy Conversion Efficiency by Incorporating Photoelectric Responsiveness into Multiporous Ionic Membrane.

The evolution of porous membranes has revitalized their potential application in sustainable osmotic-energy conversion. However, the performance of multiporous membranes deviates significantly from the linear extrapolation of single-pore membranes, primarily due to the occurrence of ion-concentration polarization (ICP). This study proposes a robust strategy to overcome this challenge by incorporating photoelectric responsiveness into permselective membranes. By introducing light-induced electric fields within the membrane, the transport of ions is accelerated, leading to a reduction in the diffusion boundary layer and effectively mitigating the detrimental effects of ICP. The developed photoelectric-responsive covalent-organic-framework membranes exhibit an impressive output power density of 69.6 W m-2 under illumination, surpassing the commercial viability threshold by ≈14-fold. This research uncovers a previously unexplored benefit of integrating optical electric conversion with reverse electrodialysis, thereby enhancing energy conversion efficiency.

Differential heat-response characteristics of two plastid isoforms of triose phosphate isomerase in tomato.

Heat stress causes dysfunction of the carbon-assimilation metabolism. As a member of Calvin-Benson-Bassham (CBB) cycle, the chloroplast triose phosphate isomerases (TPI) catalyse the interconversion of glyceraldehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP). The tomato (Solanum lycopersicum) genome contains two individual SlTPI genes, Solyc10g054870 and Solyc01g111120, which encode the chloroplast-located proteins SlTPI1 and SlTPI2, respectively. The tpi1 and tpi2 single mutants had no visible phenotypes, but the leaves of their double mutant lines tpi1tpi2 had obviously reduced TPI activity and displayed chlorotic variegation, dysplasic chloroplasts and lower carbon-assimilation efficiency. In addition to altering carbon metabolism, proteomic data showed that the loss of both SlTPI1 and SlTPI2 severely affected photosystem proteins, reducing photosynthetic capacity. None of these phenotypes was evident in the tpi1 or tpi2 single mutants, suggesting that SlTPI1 and SlTPI2 are functionally redundant. However, the two proteins differed in their responses to heat stress; the protein encoded by the heat-induced SlTPI2 showed a higher level of thermotolerance than that encoded by the heat-suppressed SlTPI1. Notably, heat-induced transcription factors, SlWRKY21 and SlHSFA2/7, which negatively regulated SlTPI1 expression and positively regulated SlTPI2 expression, respectively. Our findings thus reveal that SlTPI1 and SlTPI2 have different thermostabilities and expression patterns in response to heat stress, which have the potential to be applied in thermotolerance strategies in crops.

ETHYLENE-INSENSITIVE 3-LIKE 2 regulates ß-carotene and ascorbic acid accumulation in tomatoes during ripening.

ETHYLENE-INSENSITIVE 3/ETHYLENE-INSENSITIVE 3-LIKEs (EIN3/EILs) are important ethylene response factors during fruit ripening. Here, we discovered that EIL2 controls carotenoid metabolism and ascorbic acid (AsA) biosynthesis in tomato (Solanum lycopersicum). In contrast to the red fruits presented in the wild type (WT) 45 d after pollination, the fruits of CRISPR/Cas9 eil2 mutants and SlEIL2 RNA interference lines (ERIs) showed yellow or orange fruits. Correlation analysis of transcriptome and metabolome data for the ERI and WT ripe fruits revealed that SlEIL2 is involved in ß-carotene and AsA accumulation. ETHYLENE RESPONSE FACTORs (ERFs) are the typical components downstream of EIN3 in the ethylene response pathway. Through a comprehensive screening of ERF family members, we determined that SlEIL2 directly regulates the expression of 4 SlERFs. Two of these, SlERF.H30 and SlERF.G6, encode proteins that participate in the regulation of LYCOPENE-ß-CYCLASE 2 (SlLCYB2), encoding an enzyme that mediates the conversion of lycopene to carotene in fruits. In addition, SlEIL2 transcriptionally repressed L-GALACTOSE 1-PHOSPHATE PHOSPHATASE 3 (SlGPP3) and MYO-INOSITOL OXYGENASE 1 (SlMIOX1) expression, which resulted in a 1.62-fold increase of AsA via both the L-galactose and myoinositol pathways. Overall, we demonstrated that SlEIL2 functions in controlling ß-carotene and AsA levels, providing a potential strategy for genetic engineering to improve the nutritional value and quality of tomato fruit.

Visible Light-Mediated Selective Aerobic Oxidation of Alcohols Catalyzed by Disulfide in Batch and Flow.

Selective aerobic oxidation of alcohols in batch and flow can be realized under light irradiation, utilizing disulfide as the photocatalyst, and a variety of primary and secondary alcohols were converted to the corresponding aldehydes or ketones in up to 99% yield and high selectivity. The reaction efficiency could be increased even further by combining a continuous-flow strategy. Detailed mechanistic studies have also been achieved to determine the role of oxygen and disulfides in this oxidation.

Discovery of Daclatasvir as a potential PD-L1 inhibitor from drug repurposing.

This study employed a drug repositioning strategy to discover novel PD-L1 small molecule inhibitors. 3D-QSAR pharmacophore models were establishedand subsequently validated through various means to select a robust model, Hypo-1, suitable for virtual screening. Hypo1 was used toscreen a library of 7,475 compounds from the Drugbank database, leading to the identification of 283 molecules following molecular docking with PD-L1.19 compounds underwent HTRF assays, with 15 showing varying degrees of inhibition of the PD-1/PD-L1 interaction. Compounds2202,2204,2207, and2208were further confirmed to bind to PD-L1 using SPR experiments. Among them, compound2204(Daclatasvir, KD = 11.4 µM) showeda higher affinity for human PD-L1 than the control compound BMS-1. In the HepG2/Jurkat cell co-culture model, Daclatasvir effectively activated Jurkat cells to kill HepG2 cells. In the mouse H22 hepatocellular tumor model, Daclatasvir significantly inhibited tumor growth (TGI = 53.4 % at a dose of 100 mg/kg). Its anti-tumor effect was more pronounced when combined with Lenvatinib (TGI = 85.1 %). Flow cytometry analysis of splenocytes and tumor cells indicated that Daclatasvir activated the immune system in both models. In summary, Daclatasvir was identified as a novel PD-L1small molecule inhibitor.

Influence of malnutrition according to the glim criteria on the chemotherapy toxicities in patients with advanced lung cancer.

BACKGROUND: Cancer-associated malnutrition is highly prevalent in advanced lung cancer, and 50% of global cancer-related deaths are attributed to cancer-associated malnutrition. Platinum-containing chemotherapy is the standard treatment for advanced lung cancer. Unfortunately, it can cause exacerbated toxicities, which can also have a negative impact on patient's prognosis and quality of life. The Global Leadership Initiative on Malnutrition (GLIM) criteria have been proposed as the world's first accepted diagnostic criteria for malnutrition. However, the effectiveness of GLIM criteria in predicting chemotherapy toxicities in patients with advanced lung cancer is unclear. The aim of this study was to apply the GLIM criteria to assess the prevalence of pre-treatment diagnosis of malnutrition in patients with advanced non-small cell lung cancer (NSCLC) and to determine the impact of nutritional status on patient's chemotherapy toxicity. METHODS: We conducted a study of hospitalized patients with pathologically and clinically diagnosed advanced NSCLC who presented to our hospital from May 2021 to January 2022. Initially, the Nutritional Risk Screening-2002 (NRS-2002) was used for nutritional risk screening, and nutritional status was assessed using the Scored Patient-Generated Subjective Global Assessment (PG-SGA) and GLIM criteria. Chemotherapy toxicity was assessed and graded according to CTCAE5.0, and chemotherapy efficacy was assessed according to RECIST1.1. Kappa test was used to analyze the agreement between PG-SGA and GLIM criteria. Univariate and multivariate logistic regression analyses were used to determine the relationship between malnutrition and chemotherapy toxicity. RESULTS: A total of 215 patients with advanced NSCLC were evaluated for nutritional status. Most of the patients had normal BMI (61.86%) before the start of treatment, 40% were well-nourished as assessed by the PG-SGA tool, and 51.17% were well-nourished as assessed by GLIM criteria. Consistency analysis showed moderate agreement (Kappa = 0.463, P < 0.001) and their correlation was also moderate (Spearman, rs = 0.475, P < 0.001). The objective response rate (ORR) (P = 0.040) and disease control rate (DCR) (P < 0.001) were significantly lower in malnourished patients diagnosed according to GLIM criteria than in well-nourished patients. Multivariate analysis showed that malnutrition (OR = 1.531,95%CI 0.757-3.009; OR = 6.623,95%CI 1.390-31.567, P = 0.046) diagnosed by GLIM criteria was an independent predictor of chemotherapy toxicity. Conclusions Malnutrition diagnosed by GLIM criteria better predicts toxicity during chemotherapy, determines the degree of clinical benefit of chemotherapy, and may affect patient prognosis.

Clinical efficacy and safety of transvaginal natural orifice transluminal endoscopic surgery for benign adnexal disease: a prospective trial.

BACKGROUND: There is a scarcity of prospective clinical research evidence regarding the utilization of transvaginal natural orifice translumenal endoscopic surgery (vNOTES) as a treatment option for ovarian cysts. The objective of this study was to assess the feasibility and safety of employing vNOTES for the management of ovarian cysts. METHODS: Our study included women between the ages of 18 and 70 who intended to undergo surgical intervention for benign lesions. Stratified blocked randomization was employed to allocate participants into groups. The main objective was to assess whether the assigned group adhered to the recommended surgical technique for ovarian cystectomy or adnexectomy, without any deviation to alternative surgical methods. RESULTS: A total of 196 patients were included in the study, with all surgeries in each group being conducted according to the assigned procedures. Among them, the ovarian cystectomy layer included 58 cases in the vNOTES group and 58 cases in the conventional laparoscopy (CL) groups. The adnexectomy layer included 40 cases in the vNOTES group and 40 cases in the CL group. Utilizing a sensitivity analysis, the two-sided 95% lower confidence limit was determined to be 5.5% for the disparity in proportions between the vNOTES groups and CL groups. These lower limits fell below the predetermined non-inferiority margin of 10%. CONCLUSIONS: The study findings demonstrate that vNOTES was not inferior to CL in terms of adnexectomy or ovarian cystectomy. vNOTES can be considered a more minimally invasive surgical approach, as it results in reduced postoperative pain, faster recovery, and absence of visible incisions. Overall, vNOTES proves to be a safe, feasible, and less invasive treatment option. TRIAL REGISTRATION: This study retrospectively registered with the China Clinical Trial Registry with the registration number ChiCTR2100052223(22-10-2021).

A retrospective clinical analysis of 11 cases of PEComa from different sites.

PURPOSE: The objective of this paper is to offer a thorough examination of the clinical presentations, etiology, and treatment strategies associated with perivascular epithelioid cell tumors (PEComas). METHODS: This retrospective study examined the comprehensive archival data of PEComa cases diagnosed at Beijing Hospital from 2015 to 2023. The pathology slides of all patients were thoroughly reassessed by two experienced pathologists. A thorough retrospective analysis was undertaken, incorporating clinicopathological data including gender, age at diagnosis, initial clinical manifestations, signs, disease onset site, tumor markers, imaging findings, therapeutic modalities, pathological features, immunohistochemical profiles, treatment responses, and prognostic indicators. Patients were evaluated for disease severity according to established pathological classification criteria and were followed up until the designated analysis cut-off date. In instances where patients were unable to be monitored on-site, they were contacted via telephone for postoperative follow-up inquiries. RESULTS: This study included 11 patients with ages ranging from 17 to 66 years old, presenting with the disease in multiple anatomical sites, including the retroperitoneum (2/11), liver (4/11), kidney (4/11), lung (1/11), and broad ligament of the uterus (1/11). Most patients presented with non-specific clinical symptoms and were subsequently diagnosed with space-occupying lesions upon physical examination. The tumor demonstrated progressive growth and enlargement, which could result in compression of neighboring organs. Preoperative imaging alone is insufficient for a definitive diagnosis of PEComa, but MRI can provide an initial evaluation of the tumor's potential malignancy. Molecular marker testing specific to PEComa, such as HMB-45 (90.0%), SMA (81.8%), Melan-A (90.9%), vimentin (90.9%), and Desmin (36.3%), was conducted on all patients. No adjuvant therapies were administered postoperatively. Upon analysis, no instances of relapse at the primary site or the development of new tumors at other sites were observed. Regular imaging reviews of three patients with malignant PEComa post-surgery showed no evidence of recurrence. CONCLUSIONS: The clinical presentation, tumor biomarkers, and imaging characteristics of PEComa lack specificity, necessitating dependence on pathology and immunohistochemistry for precise diagnosis. The mainstay of treatment consists of surgical resection, with patients typically experiencing a favorable prognosis.

A DFT and kinetic study: Is it possible to prepare epoxides without catalysts using the in-situ generated peroxy radicals or peroxides by one-step method?

DFT calculations and kinetic analysis have been employed to comprehensively explore the possibility to prepare epoxides by one-step method using the in-situ generated peroxy radicals or hydroperoxides as epoxidizing agents. Computational studies demonstrated that the selectivities for the reaction systems of O2 /R2/R1, O2 /CuH/R1, O2 /CuH/styrene, O2 /AcH/R1 were 68.2%, 69.6%, 100% and 93.3%, respectively. The in-situ generated peroxide radicals, such as HOO˙, CuOO˙ and AcOO˙, could react with R1 or styrene by attacking the CC double bond to form a CO bond and subsequently undergoing a cleavage of OO bond to yield epoxides. Peroxide radicals could abstract a hydrogen atom from methyl group on R1, forming unwanted by-products. It should be noted that the hydrogen atoms of HOO˙ is easy to be abstracted by CC double bond and simultaneously the oxygen atom is connected to the CH moiety to form an alkyl peroxy radical (Rad11), greatly limiting the selectivity. The comprehensive mechanistic studies provide a deep understanding on preparing epoxides by one-step method.

Reference genome and annotation updates lead to contradictory prognostic predictions in gene expression signatures: a case study of resected stage I lung adenocarcinoma.

RNA-sequencing enables accurate and low-cost transcriptome-wide detection. However, expression estimates vary as reference genomes and gene annotations are updated, confounding existing expression-based prognostic signatures. Herein, prognostic 9-gene pair signature (GPS) was applied to 197 patients with stage I lung adenocarcinoma derived from previous and latest data from The Cancer Genome Atlas (TCGA) processed with different reference genomes and annotations. For 9-GPS, 6.6% of patients exhibited discordant risk classifications between the two TCGA versions. Similar results were observed for other prognostic signatures, including IRGPI, 15-gene and ORACLE. We found that conflicting annotations for gene length and overlap were the major cause of their discordant risk classification. Therefore, we constructed a prognostic 40-GPS based on stable genes across GENCODE v20-v30 and validated it using public data of 471 stage I samples (log-rank P < 0.0010). Risk classification was still stable in RNA-sequencing data processed with the newest GENCODE v32 versus GENCODE v20-v30. Specifically, 40-GPS could predict survival for 30 stage I samples with formalin-fixed paraffin-embedded tissues (log-rank P = 0.0177). In conclusion, this method overcomes the vulnerability of existing prognostic signatures due to reference genome and annotation updates. 40-GPS may offer individualized clinical applications due to its prognostic accuracy and classification stability.

Function-Led Design of Covalent-Organic-Framework Membranes for Precise Ion Separation.

Insufficient access to clean water and resources has emerged as one of the most pressing issues affecting people globally. Membrane-based ion separation has become a focal point of research for the generation of fresh water and the extraction of energy elements. This Review encapsulates recent advancements in the selective ion transport of covalent organic framework (COF) membranes, accomplished by strategically pairing diverse monomers to create membranes with various pore sizes and environments for specific purposes. We first discuss the merits of using COF materials as a basis for fabricating membranes for ion separation. We then explore the development of COF membranes in areas such as desalination, acid recovery, and energy element extraction, with a particular emphasis on the fundamental principles of membrane design. Lastly, we address both theoretical and practical challenges, as well as potential opportunities in the targeted design of ion-selective membranes. The goal of this Review is to stimulate future investigative efforts in this field, which is of significant scientific and strategic importance.

Leucine Supplementation Alleviates Immune and Antioxidant Function Damage in Adult Rats Induced by Early Weaning.

BACKGROUND: Early weaning (EW) can lead to stress and destroy intestinal integrity. Leucine has functional diversity in antioxidant, immune, and metabolic regulation. OBJECTIVES: This study aimed to explore the lifelong impact of EW on intestinal, immune, and antioxidant functions of adult rats and the role of leucine supplementation in the alleviation of the damage caused by EW. METHODS: In this 211-d study, 36 Sprague Dawley (SD) rat pups were divided into 3 groups: 21-d weaning normal group, 17-d EW group, and 17-d EW group with 2-mo leucine supplementation. The content of amino acids in serum, immune and antioxidant indexes, intestinal morphology, liver transcriptomics, messenger RNA (mRNA), and protein expression of signaling pathway were determined. RESULTS: EW reduced the protein expression level of secretory immunoglobulin A (IgA) and reduced glutathione (GSH) in the jejunum and increased the protein expression concentrations of IgA, IgM, and interleukin 17 (IL-17) in serum, and tumor necrosis factor α and IL-1ß in the jejunum. The impairment by EW was activated via nuclear transcription factor κB (NF-κB) signal pathway. In terms of antioxidation, EW reduced the concentration of GSH in the jejunum. After leucine supplementation, the damage induced by EW was partially repaired. CONCLUSIONS: EW causes long-term damage to the intestinal barrier function, immunity, apoptosis factor, and antioxidant function in rats and leucine supplementation could alleviate the impairment, suggesting a possible approach to EW.

Initial screening for occult congenital ectopia lentis based on ocular biological parameters in preschool children.

BACKGROUND: This study aimed to identify an initial screening tool for congenital ectopia lentis (CEL) by comparing ocular biological parameters in children with myopia. METHODS: A retrospective case-control study was conducted at one tertiary referral centre, from October 2020 to June 2022. Axial length (AL), corneal curvature (CC), refractive astigmatism (RA), corneal astigmatism (CA), internal astigmatism (IA), the difference between the axis of RA and CA [AXIS(RA-CA)], white-to-white corneal diameter (WTW), and axial length-corneal radius ratio (AL/CR) were compared in 28 eyes of CEL patients, and 60 eyes of myopic patients matched for age and refraction. The spherical equivalent of each eye was < -3.00 D. Area under the curve (AUC) of the receiver operating characteristic curves were calculated. RESULTS: The differences in RA, AL, mean keratometry (Kmed), maximum keratometry (Kmax), minimum keratometry (Kmin), CA, IA, AXIS(RA-CA), WTW, and AL/CR between the CEL and myopic groups were statistically significant (p < 0.05; p < 0.001; p < 0.001; p < 0.001; p < 0.001; p < 0.05; p < 0.001; p < 0.001; p < 0.001; p < 0.001, respectively). In logistic regression analysis RA, IA, AXIS(RA-CA), and AL/CR were significantly associated with CEL (p < 0.05). AUCs for RA, IA, AXIS(RA-CA), and AL/CR were 0.694, 0.853, 0.814, and 0.960, respectively. AUCs for AL/CR in SE< -6.00 D subgroup was 0.970, and 0.990 in -6.00 D ≤ SE < -3.00 D group. An AL/CR < 3.024 was the optimal cut-off point differentiating the CEL and control groups (sensitivity, 92.9%; specificity, 88.30%). CONCLUSIONS: A smaller AL/CR could identify CEL in children with myopia. An AL/CR cut-off value of 3.024 may be the most sensitive and specific parameter for the differential diagnosis of CEL in patients with mild to high myopia.

The Establishment of China Bronchiectasis Registry and Research Collaboration (BE-China): Protocol of a prospective multicenter observational study.

BACKGROUND: Bronchiectasis is a highly heterogeneous chronic airway disease with marked geographic and ethnic variations. Most influential cohort studies to date have been performed in Europe and USA, which serve as the examples for developing a cohort study in China where there is a high burden of bronchiectasis. The Establishment of China Bronchiectasis Registry and Research Collaboration (BE-China) is designed to: (1) describe the clinical characteristics and natural history of bronchiectasis in China and identify the differences of bronchiectasis between the western countries and China; (2) identify the risk factors associated with disease progression in Chinese population; (3) elucidate the phenotype and endotype of bronchiectasis by integrating the genome, microbiome, proteome, and transcriptome with detailed clinical data; (4) facilitate large randomized controlled trials in China. METHODS: The BE-China is an ongoing prospective, longitudinal, multi-center, observational cohort study aiming to recruit a minimum of 10,000 patients, which was initiated in January 2020 in China. Comprehensive data, including medical history, aetiological testing, lung function, microbiological profiles, radiological scores, comorbidities, mental status, and quality of life (QoL), will be collected at baseline. Patients will be followed up annually for up to 10 years to record longitudinal data on outcomes, treatment patterns and QoL. Biospecimens, if possible, will be collected and stored at - 80 °C for further research. Up to October 2021, the BE-China has enrolled 3758 patients, and collected 666 blood samples and 196 sputum samples from 91 medical centers. The study protocol has been approved by the Shanghai Pulmonary Hospital ethics committee, and all collaborating centers have received approvals from their local ethics committee. All patients will be required to provide written informed consent to their participation. CONCLUSIONS: Findings of the BE-China will be crucial to reveal the clinical characteristics and natural history of bronchiectasis and facilitate evidence-based clinical practice in China. Trial registration Registration Number in ClinicalTrials.gov: NCT03643653.

Lycopene Affects Intestinal Barrier Function and the Gut Microbiota in Weaned Piglets via Antioxidant Signaling Regulation.

BACKGROUND: In pig production, early and abrupt weaning frequently causes weaning stress, which manifests as oxidative damage, barrier disruption, and digestion and absorption capacity declines. Lycopene exhibits beneficial antioxidant capacity in both humans and other animal models. OBJECTIVES: The present study aimed to investigate the effects of lycopene supplementation on early weaning stress in piglets and the underlying mechanisms by examining the oxidative stress state, gut intestinal barrier function, and the gut microbiota. METHODS: Twenty-four 21-day-old weaned piglets [Duroc × (Landrace × Yorkshire); castrated males; 5.48 ± 0.10 kg initial body weight] were randomly assigned to 2 treatments. The piglets were fed a basal diet (control treatment) or a basal diet supplemented with 50 mg/kg lycopene (lycopene treatment) for 28 days. The serum lipid levels, serum and jejunum enzyme activities, jejunum morphology, mRNA and protein expression, and gut microbiota were determined. RESULTS: Compared with the control treatment, lycopene supplementation increased the serum catalase activity (P = 0.042; 62.0%); serum total cholesterol concentration (P = 0.020; 14.1%); and jejunum superoxide dismutase activity (P = 0.032; 21.4%), whereas it decreased serum (P = 0.039, 23.0%) and jejunum (P = 0.047; 20.9%) hydrogen peroxide concentrations. Additionally, lycopene increased the mRNA and protein expression of NFE2-like bZIP transcription factor 2 (214.0% and 102.4%, respectively) and CD36 (100.8% and 145.2%, respectively) in the jejunum, whereas it decreased the mRNA and protein expression of Kelch-like ECH-associated protein 1 (55.6% and 39.8%, respectively ). Lycopene also improved jejunal morphology, increasing the villus height (P = 0.018; 27.5%) and villus:crypt ratio (P < 0.001; 57.9%). Furthermore, it increased the abundances of potentially beneficial bacterial groups, including Phascolarctobacterium and Parasutterella, and decreased those of potentially pathogenic bacterial groups, including Treponema_2 and Prevotellaceae_unclassified. CONCLUSIONS: Lycopene supplementation strengthens the intestinal barrier function and improves the gut microbiota in weaned piglets by regulating intestinal antioxidant signaling.

Expression characteristic, immune signature, and prognosis value of EFNA family identified by multi-omics integrative analysis in pan-cancer.

BACKGROUND: EphrinA (EFNA) are Eph receptor ligands that regulate various disease processes. Nonetheless, the expression characteristics of EFNAs in pan-cancer, their relationship with tumor immune microenvironment, and prognostic value landscape remain unknown. METHODS: A comprehensive landscape of EFNAs was created using various statistical data extracted from 33 cancers. Subsequently, we identified differential expression, genetic variations, potential function enrichment, tumor immune-related analysis, and drug sensitivity. Further, we investigated the clinical features and diagnostic prognostic value of EFNAs. RT-qPCR, western blot and immunohistochemistry (IHC) were used to validate the expression level and significant clinical value of EFNA5 in lung adenocarcinoma cell lines and tissues. RESULTS: EFNAs were highly mutated in various cancers. Genomic and epigenetic alterations of EFNAs were observed in various tumors, where an oncogenic mutation in specific cancer types potentially affected EFNA expression. Moreover, tumor-derived EFNAs were significantly related to the tumor immune microenvironment, suggesting that they are promising therapeutic targets. The majority of EFNA family genes were significantly linked to patient prognosis. Eventually, EFNA5 was an independent prognostic factor in lung adenocarcinoma. CONCLUSION: In summary, EFNAs are crucial in tumor immune regulation, and EFNA5 is a prognostic marker in lung adenocarcinoma. Our findings provide new insights into EFNAs from a bioinformatics standpoint and highlight the significance of EFNAs in cancer diagnosis and treatment.

SbbHLH85, a bHLH member, modulates resilience to salt stress by regulating root hair growth in sorghum.

bHLH family proteins play an important role in plant stress response. However, the molecular mechanism regulating the salt response of bHLH is largely unknown. This study aimed to investigate the function and regulating mechanism of the sweet sorghum SbbHLH85 during salt stress. The results showed that SbbHLH85 was different from its homologs in other species. Also, it was a new atypical bHLH transcription factor and a key gene for root development in sweet sorghum. The overexpression of SbbHLH85 resulted in significantly increased number and length of root hairs via ABA and auxin signaling pathways, increasing the absorption of Na+. Thus, SbbHLH85 plays a negative regulatory role in the salt tolerance of sorghum. We identified a potential interaction partner of SbbHLH85, which was phosphate transporter chaperone PHF1 and modulated the distribution of phosphate, through screening a yeast two-hybrid library. Both yeast two-hybrid and BiFC experiments confirmed the interaction between SbbHLH85 and PHF1. The overexpression of SbbHLH85 led to a decrease in the expression of PHF1 as well as the content of Pi. Based on these results, we suggested that the increase in the Na+ content and the decrease in the Pi content resulted in the salt sensitivity of transgenic sorghum.

Sarcopenia is an independent risk factor for depression in patients with advanced lung cancer.

BACKGROUND: Depression is the most prevalent psychological issue among cancer patients and can seriously affect patients' life and disease prognosis and even lead to suicide. Sarcopenia is a manifestation of cancer cachexia, a chronic progressive process. It is accompanied by a sustained decrease in skeletal muscle mass, muscle strength, and physical function and likewise has various negative effects on the patient. This study aimed to evaluate sarcopenia and other factors that may affect depression in patients with lung cancer and to further analyze and discuss. METHODS: A total of 104 eligible patients were enrolled in this cross-sectional study, using the Hamilton Depression Scale to assess depression, obtaining the psoas muscle index (PMI) by computed tomography (CT), and performing the diagnosis of sarcopenia. Clinical and personal characteristics were collected by electronic medical records. RESULTS: We evaluated a total of 104 hospitalized cancer patients in this analysis, with mean age = 57.8 ± 11.0 years, and 65.38% (68) were female. We found that up to 31.7% (33) of the participants had depression and 61.5% (64) of the participants had sarcopenia, and no statistical differences were found among depressed and non-depressed patients in relation to age, smoking, gender, performance status, and pathology. Patients with sarcopenia have more than four times the risk of suffering from depression than patients without sarcopenia (OR = 4.133, 95%CI = 1.390-12.287; p = 0.011). Similarly, the possibility of depression in patients with PD (progressive disease) as efficacy evaluation increased by 13.482 times (95%CI = 2.121-85.679, p = 0.006). CONCLUSION: In individuals with terminal lung cancer, depression and sarcopenia are prevalent. A strong association between the two is now thought to exist. Sarcopenia and efficacy evaluation are independent risk factors for depression. The correlation between sarcopenia and depression underscores the need for early intervention by our clinicians.