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BackgroundRecently, a sum of trials of programmed cell death-1 (PD-1) inhibitors combined with chemotherapy have shown excellent efficacy compared to chemotherapy alone in patients with previously untreated, advanced esophageal squamous cell carcinoma (ESCC). However, there is no head-to-head comparison and consensus on which immunotherapy regimen results in better survival outcomes. This study aimed to evaluate the survival efficacy of various PD-1 inhibitor–based therapies in the first-line treatments for patients with advanced ESCC.MethodsData collected prior to 31 July 2023 were searched in the PubMed, Cochrane Library, Embase, Medline, and Web of Science databases. Overall survival (OS) and progression-free survival curves were pooled using the MetaSurv package. Survival data were compared by reconstructed individual patient data.ResultsA total of 4,162 patients and seven randomized controlled trials were included. After synthesizing, PD-1 inhibitors prolonged median OS from 11.3 months (95% CI (confidence interval) 10.7–11.7) to 15.6 months (95% CI 14.7–16.3). Based on reconstructed patient-level data, the toripalimab, tislelizumab, and sintilimab group achieved the longest OS, whereas the sintilimab and tislelizumab group had the lowest risk of recurrence than other treatments. In patients with a combined positive score of ≥10, sintilimab had better OS efficacy than pembrolizumab (HR: 0.71, 95% CI: 0.52–0.96). In terms of tumor proportion score of ≥1%, camrelizumab, nivolumab, and toripalimab showed proximate survival benefits in both OS and progression-free survival.ConclusionPD-1 inhibitor combined with chemotherapy significantly improved the survival time of patients with advanced ESCC. Toripalimab, tislelizumab, and sintilimab plus chemotherapy showed the best OS benefit. Longer progression-free benefits might be generated from adding tislelizumab and sintilimab to chemotherapy. Sintilimab was strongly recommended for patients with high programmed cell death–ligand 1 abundance.Systematic Review Registration:[https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42024501086].

Vascular dementia (VD), a chronic syndrome of acquired intellectual impairment resulting from cerebrovascular diseases, is closely linked to neuronal autophagy and apoptosis. As a standardized extract from Ginkgo biloba L. leaves, EGb761 is widely applied for treating cerebrovascular diseases owing to its neuroprotective effects, with on-going research exploring its therapeutic mechanisms. Rat model of VD and SH-SY5Y cell model with OGD/R injury was applied for this study. Results showed that EGb761 reduces OGD/R-elicited apoptosis and autophagosome production, whereas improving the viability of hippocampal neurons. EGb761 treatment led to a decrease in the ratios of p-AMPK/AMPK, Bax/Bcl-2, cleaved caspase-3/caspase-3, cleaved caspase-9/caspase-9, LC3-II/LC3-I, and level of Beciln-1, as well as enhancing the proportion of p-mTOR/mTOR. Additionally, EGb761 indicated a protective effect on rats' cognitive function. These results demonstrated EGb761′s specific therapeutic mechanism in preventing apoptosis and autophagy in VD models and improving cognitive functioning in VD rats through AMPK-mTOR signalling.

ObjectiveThe safety results of different recommended doses of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) for patients with type 2 diabetes mellitus (T2DM) remain uncertain. This study aims to comprehensively estimate and rank the relative safety outcomes with different doses of SGLT-2i for T2DM.MethodsPubMed, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Chinese National Knowledge Infrastructure, WanFang database, and SinoMed database were searched from the inception to 31 May 2023. We included double-blind randomized controlled trials (RCTs) comparing SGLT-2i with placebo or another antihyperglycemic as oral monotherapy in the adults with a diagnosis of T2DM.ResultsTwenty-five RCTs with 12,990 patients randomly assigned to 10 pharmacological interventions and placebo were included. Regarding genital infections (GI), all SGLT-2i, except for ertugliflozin and ipragliflozin, were associated with a higher risk of GI compared to placebo. Empagliflozin 10mg/d (88.2%, odds ratio [OR] 7.90, 95% credible interval [CrI] 3.39 to 22.08) may be the riskiest, followed by empagliflozin 25mg/d (83.4%, OR 7.22, 95%CrI 3.11 to 20.04)) and canagliflozin 300mg/d (70.8%, OR 5.33, 95%CrI 2.25 to 13.83) based on probability rankings. Additionally, dapagliflozin 10mg/d ranked highest for urinary tract infections (UTI, OR 2.11, 95%CrI 1.20 to 3.79, 87.2%), renal impairment (80.7%), and nasopharyngitis (81.6%) when compared to placebo and other treatments. No increased risk of harm was observed with different doses of SGLT-2i regarding hypoglycemia, acute kidney injury, diabetic ketoacidosis, or fracture. Further subgroup analysis by gender revealed no significantly increased risk of UTI. Dapagliflozin 10mg/d (91.9%) and canagliflozin 300mg/d (88.8%) ranked first in the female and male subgroups, respectively, according to the probability rankings for GI.ConclusionCurrent evidence indicated that SGLT-2i did not significantly increase the risk of harm when comparing different doses, except for dapagliflozin 10mg/d, which showed an increased risk of UTI and may be associated with a higher risk of renal impairment and nasopharyngitis. Additionally, compared with placebo and metformin, the risk of GI was notably elevated for empagliflozin 10mg/d, canagliflozin 300mg/d, and dapagliflozin 10mg/d. However, it is important to note that further well-designed RCTs with larger sample sizes are necessary to verify and optimize the current body of evidence.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023396023.

Abstract Coreopsis tinctoria Nutt. has been widely cultivated in Xinjiang, Yunnan as well as other western regions of China. In folk medicine, the flower tea C. tinctoria is often used as an adjunctive therapy for diabetes and Alzheimer's disease. To explore the chemicals responsible for the health benefits of C. tinctoria, a water‐soluble polysaccharide (CT70‐1) was isolated from C. tinctoria. The structure feature analyses revealed that CT70‐1 was a heteropolysaccharide with a relative molecular weight of 2.1×103 Da. It consisted of α‐D‐Glcp‐(1→, →4)‐α‐D‐Glcp‐(1→, →5)‐α‐L‐Araf‐(1→, →6)‐2‐OAc‐β‐D‐Galp‐(1→, →3)‐α‐L‐Rhap‐(1→, →3,6)‐β‐D‐Manp‐(1→, →6)‐β‐D‐Manp‐(1→, →1,6)‐β‐D‐Fruf‐(2→, α‐L‐Araf‐(1→, and →3)‐β‐D‐Manp‐(1→. Further, CT70‐1 exhibited α‐amylase and α‐glucosidase inhibitory activity with IC50 values of 2.79 ± 0.17 mM and 3.00 ± 0.02 mM, respectively. Moreover, CT70‐1 significantly inhibited lipopolysaccharide‐stimulated nitric oxide production of RAW264.7 and BV2 cells with IC50 values of 0.07 mM and 0.12, respectively. In conclusion, the above findings provide a foundation for promising natural ingredient CT70‐1 in the food and pharmaceutical industries.

The heat input during laser welding process has significant influence on microstructure and properties of the joints, whereas there is currently limited research concerning the influence of heat input during laser welding process of β titanium alloys. The microstructure and tensile properties of laser welded Ti–3Al–6Mo–2Fe–2Zr (wt.%) joints under different heat inputs were investigated in this paper. Numerical simulation process was used to explain the microstructure evolution in HAZ and fusion zone. The microstructure of HAZ is divided into three different regions from fusion line to base metal. In near-HAZ, mid-HAZ, and far-HAZ, the microstructures are composed of single β phase, β + αp, and β + αp + retained αs, respectively. In fusion zone, the microstructure consists of single β phase because of the fast cooling rate and high content of β stabilizing elements. The ultimate tensile strength (UTS) of laser welded specimens is lower than that of base metal due to the lack of strengthening phase and the coarsening of β grains. Higher heat input further exacerbates the coarsening of β grains in the fusion zone and HAZ, which consequently results in the decrement of UTS of the joints.

Abstract Background Red yeast rice (RYR), a nutraceutical with a profound cholesterol-lowering effect, was found to attenuate non-alcoholic fatty liver disease (NAFLD) in mice. Despite monacolin K in RYR being a specific inhibitor of hydroxymethylglutaryl-coenzyme A reductase (HMCGR), the mechanisms underlying the protective effects of RYR against NAFLD are not fully elucidated. Methods Using a mouse model of high-fat diet (HFD) feeding and a cellular model of HepG2 cells challenged by lipopolysaccharide (LPS) and palmitic acid (PA), the possible molecular mechanisms were exploited in the aspects of NF-κB/NLRP3 inflammasome and mTORC1-SREBPs signaling pathways by examining the relevant gene/protein expressions. Subsequently, the correlation between these two signals was also verified using cellular experiments. Results RYR ameliorated lipid accumulation and hepatic inflammation in vivo and in vitro. RYR improved lipid metabolism through modulating mTORC1-SREBPs and their target genes related to triglyceride and cholesterol synthesis. Furthermore, RYR suppressed hepatic inflammation by inhibiting the NF-κB/NLRP3 inflammasome signaling. Interestingly, the treatment with RYR or MCC950, a specific NLRP3 inhibitor, resulted in the reduced lipid accumulation in HepG2 cells challenged by LPS plus PA, suggesting that the inhibitory effects of RYR on NLRP3 inflammasome-mediated hepatic inflammation may partially, in turn, contribute to the lipid-lowering effect of RYR. Conclusions The modulation of NF-κB/NLRP3 inflammasome and lipid synthesis may contribute to the ameliorative effects of RYR against HFD-induced NAFLD.

The electrolysis of water for sustainable hydrogen producing is a crucial segment of various emerging clean-energy technologies. However, pursuing an efficient and cheap alternative catalyst to substitute state-of-the-art platinum-group electrocatalysts remains a prerequisite for the commercialization of this technology. Typically, precious-metal-free catalysts have always much lower activities towards hydrogen production than that of Pt-group catalysts. To explore high-performance catalysts, maximally exposed active sites, rapid charge transfer ability and desirable electronic configuration are essentially demanded. Herein, the fundamentals of hydrogen evolution reaction will be briefly described and the main focus will be on the interfacial engineering strategies by means of constructing defect structure, creating heterojunction, phase engineering, lattice strain control, designing hierarchical architecture and doping heteroatoms to effectively proliferate the catalytic active sites, facilitate the electron diffusion and regulate the electronic configuration of numerous transition metals and their nitrides, carbides, sulfides, phosphides as well as oxides, achieving a benchmark performance of platinum-free electrocatalysts for the hydrogen evolution reaction. This review unambiguously offers proof that the conventional cheap and earth-abundant transition metal-based substances can be translated into an active water splitting catalyst by the rational and controllable interfacial designing.

Recent research efforts have shown that tea has activities against SARS-CoV-2. However, the active compounds and the action mechanisms are largely unknown. Here we study the inhibitory potential of L-theanine from tea and its semi-synthesized derivative, a small-molecule fluorescent compound, ethyl 6-bromocoumarin-3-carboxylyl L-theanine (TBrC) against infection and replication of SARS-CoV-2 and the underlying mechanisms of action. We reveal that TBrC has potential activities against SARS-CoV-2 in addition to its activity against lung cancer. TBrC showed extracellular inhibition of SARS-CoV-2 Mpro/3CL and the host cell receptor ACE2 while interacting with the viral spike glycoproteins (wild-type, Delta, and Omicron mutants). Moreover, TBrC and L-theanine significantly suppressed growth and TNFα-induced nuclear transcriptional activation of NF-κB in human lung cancer cells without affecting the viability of normal lung cells, suggesting a potential protection of TBrC and L-theanine from pulmonary damages in SARS-CoV-2 infected patients, especially for lung cancer patients with SARS-CoV-2 infection.

Alhagi pseudalhagi Desv. Extract (APE) is the major active fraction extracted from the aerial part of Alhagi pseudalhagi Desv. In view of its application in Uyghur medicine, it may be beneficial for the treatment of ulcerative colitis (UC). The aim of the present study was to investigate the possible beneficial effects of APE on UC mice and detect the possible mechanisms underlying these effects.Methods: An acute UC model was established in mice using dextran sulfate sodium. Sixty mice were randomly divided into six groups: normal, UC model, sulfasalazine (200 mg/kg), high-dose APE (APE-H, 2.82 g/kg), middle-dose APE (APE-M, 1.41 g/kg), and low-dose APE (APE-L, 0.70 g/kg) groups. Drugs were administered by gavage for 10 days after the induction of colitis. Serum and colon tissue samples were collected from the mice during the experiment, and survival signs, body weight changes, disease activity index (DAI), colon length, and colon wet weight in mice were determined after the treatment. UC-induced damage, including inflammation and ulceration of colon mucosa, were observed by the naked eye as well as using hematoxylin and eosin staining (H&E) and scanning electron microscopy and scored according to Wallace and Keean’s criteria. We measured the levels of tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6, and IL-10 in the serum and colon tissues using ELISA. Additionally, the relative protein levels of toll-like receptor 4 (TLR4), nuclear factor-kappa B p65 (NF-κB p65), phosphorylated NF-κB p65 at Ser536 (p-p65 Ser536), inhibitor kappa B-kinase ß (IK-Kβ), and phosphorylated IK-Kβ (Ser176/180) (p-IK-Kβ) in colonic mucosal epithelial tissues were detected using western blotting. The main functional components of APE were analyzed and confirmed by UPLC-MS/MS.Results: APE treatment repaired the UC-induced colon mucosa injury, reduced the weight loss, attenuated DAI, colon macroscopic damage index, and histological inflammation, and significantly downregulated the levels of inflammatory markers, including TNF-α, IL-1β, and IL-6, in the serum and colon tissues. Additionally, APE treatment reduced the levels of TLR4 and phosphorylation of p-NF-κB and p-IK-Kβ. The main components of APE are taxifolin, 3,5-dihydroxy-2-(4-hydroxyphenyl)-7-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl) oxan-2-yl] oxychromen-4-one, hyperoside, rutin, kaempferol, isorhamnetin, 7,8-dihydroxyflavone, and kaempferide.Conclusions: To the best of our knowledge, the present study is first to demonstrate that APE exerts a protective effect against intestinal inflammation in UC by affecting TLR4-dependent NF-κB signaling pathways.

The discovery of circular RNA (circRNA) greatly complements the traditional gene expression theory. CircRNA is a class of non-coding RNA with a stable cyclic structure. They are highly expressed, spatiotemporal-specific and conservative across species. Importantly, circRNA participates in the occurrence of many kinds of tumors and regulates the tumor development. Glioma is featured by limited therapy and grim prognosis. Cancer-associated circRNA compromises original function or creates new effects in glioma, thus contributing to oncogenesis. Therefore, this article reviews the biogenesis, metabolism, functions and properties of circRNA as a novel potential biomarker for gliomas. We elaborate the expression characteristics, interaction between circRNA and other molecules, aiming to identify new targets for early diagnosis and treatment of gliomas.

Data are a strategic resource for industrial production, and an efficient data-mining process will increase productivity. However, there exist many missing values in data collected in real life due to various problems. Because the missing data may reduce productivity, missing value imputation is an important research topic in data mining. At present, most studies mainly focus on imputation methods for continuous missing data, while a few concentrate on discrete missing data. In this paper, a discrete missing value imputation method based on a multilayer perceptron (MLP) is proposed, which employs a momentum gradient descent algorithm, and some prefilling strategies are utilized to improve the convergence speed of the MLP. To verify the effectiveness of the method, experiments are conducted to compare the classification accuracy with eight common imputation methods, such as the mode, random, hot-deck, KNN, autoencoder, and MLP, under different missing mechanisms and missing proportions. Experimental results verify that the improved MLP model (IMLP) can effectively impute discrete missing values in most situations under three missing patterns.

Laser-arc hybrid welding of AZ31B magnesium alloy was carried out in this paper, and the effects of welding parameters (laser power, welding speed, welding current) on weld formation, microstructure evolution and mechanical property were studied. The results showed that laser-arc hybrid welding can inhibit the undercut defect during laser welding on the one hand, and enhance the arc stability on the other hand. The penetration depth and width showed no significant relation with the total heat input, but were linear related to the laser heat input and the arc heat input, respectively. The average grain size of the equiaxed grains was closely related to the heat input. The higher the heat input was, the larger the grains. The optimized welding parameters were laser power of 3.5 kW, welding speed of 1.8 m/min and welding current of 100 A. In this case, the weld was free of undercut and pores, and the tensile strength and elongation rate reached 190 MPa and 12%, respectively.

The enumeration of inversion sequences avoiding a single pattern was initiated by Corteel--Martinez--Savage--Weselcouch and Mansour--Shattuck independently. Their work has sparked various investigations of generalized patterns in inversion sequences, including patterns of relation triples by Martinez and Savage, consecutive patterns by Auli and Elizalde, and vincular patterns by Lin and Yan. In this paper, we carried out the systematic study of inversion sequences avoiding two patterns of length $3$. Our enumerative results establish further connections to the OEIS sequences and some classical combinatorial objects, such as restricted permutations, weighted ordered trees and set partitions. Since patterns of relation triples are some special multiple patterns of length $3$, our results complement the work by Martinez and Savage. In particular, one of their conjectures regarding the enumeration of $(021,120)$-avoiding inversion sequences is solved.

Photoluminescence (PL) bands from potassium dihydrogen phosphate (KDP) crystals are studied by time-resolved PL spectroscopy. KDP crystals irradiated at a laser fluence of 11.5 J/cm2 are found to have the highest probability of phosphorus–oxygen hole center defects and the lowest probability of phosphorus-oxygen electric center defects, in contrast to the probabilities of these defects for KDP crystals irradiated at 9.0 J/cm2. The probabilities of these two defects occurring in retired components are found to be intermediate between those for crystals irradiated at the two different fluences. The two types of defects may result from two different mechanisms and may interconvert under certain conditions. Thus, there are differences between the defects in KDP crystals irradiated at a high laser fluence and those in retired components.

Background/Aims: Thyroid cancer is the most common malignancy in human endocrine system. Smad ubiquitination regulatory factor 1 (Smurf1) is an E3 ubiquitin-protein ligase in ubiquitin-proteasome pathway (UPP) system. This study aimed to investigate the effects of Smurf1 on thyroid cancer proliferation and metastasis, as well as underlying potential mechanism. Methods: The expression levels of Smurf1 in thyroid tumor tissues and thyroid cancer cells were detected by western blotting and qRT-PCR. Then, the effects of up-regulation or down-regulation of Smurf1 on thyroid cancer cell viability, migration, invasion, proliferation and apoptosis were measured using trypan blue exclusion assay, two-chamber migration (invasion) assay, cell colony formation assay and Guava Nexin assay, respectively. The ubiquitination of kisspeptin-1 (KISS-1) was assessed by protein ubiquitination assay. Finally, the effects of KISS-1 overexpression on activity of nuclear factor-kappa B (NF-κB) signaling pathway, as well as thyroid cancer cell viability, migration, invasion, proliferation and apoptosis were also detected, respectively. Results: Smurf1 was highly expressed in thyroid tumor tissues and thyroid cancer cells. Up-regulation of Smurf1 promoted the viability, migration, invasion and proliferation of thyroid cancer cells. Knockdown of Smurf1 had opposite effects. Moreover, smurf1 promoted the ubiquitination of KISS-1. Overexpression of KISS-1 inactivated NF-κB pathway, suppressed thyroid cancer cell viability, migration, invasion and proliferation, and induced cell apoptosis. Conclusion: Up-regulation of Smurf1 exerted important roles in thyroid cancer formation and development by promoting thyroid cancer proliferation and metastasis. The ubiquitin-dependent degradation of KISS-1 induced by Smurf1 and the activation of NF-κB signaling pathway might be involved in this process. Smurf1 could be an effective therapy target and biomarker for thyroid cancer treatment.

The effects of α-linolenic acid (ALA)-rich flaxseed oil (FDO) against ethanol-induced liver injury and the probable molecular mechanisms in a mouse model of chronic-plus-single-binge ethanol feeding were evaluated. Mice were fed Lieber-DeCarli ethanol or control liquid diets with corn oil (CNO) or flaxseed oil for 10 days. On day 11, mice are gavaged with a single dose of ethanol or maltose dextrin. Ethanol exposure with CNO caused severe liver injury, inflammation and oxidative stress in liver, which were remarkably ameliorated by FDO. FDO supplementation decreased the elevation of plasma endotoxin level, which might be attributed to ameliorating ethanol-induced intestinal barrier dysfunction via upregulating the expressions of tight junction proteins. Additionally, FDO supplementation suppressed endotoxin-triggered inflammation via blocking TLR4/MyD88/NF-κB cascades in liver. These findings suggest that ALA-rich flaxseed oil may have potential to be developed as an effective agent for ethanol-induced liver injury.

In order to get products with antioxidant activity from Arca subcrenata Lischke, the optimal hydrolase and hydrolysis conditionswere investigated in the paper. Three proteases (neutrase, alcalase and papain) were applied to hydrolyze the homogenate of A. subcrenata. An orthogonaldesign was used to optimize hydrolysis conditions, and the pH-stat methods was used to determine the degree of hydrolysis. Viewed from the angle ofreducing power, such as scavenging activities against α,α-diphenyl-β-picrylhydrazyl (DPPH) radical and hydrogen peroxide, the antioxidantactivities of the alcalase hydrolysate (AH) were superior to neutrase hydrolysate (NH) and papain hydrolysate (PH), and its EC50 values in DPPHradical and hydrogen peroxide scavenging effect were 6.23 mg/ml and 19.09 mg/ml, respectively. Moreover, compared with products hydrolyzed byneutrase and papain, the molecular mass of AH was lower and its content ofamino acid of peptides was higher. Therefore, alcalase was selected as theoptimal enzyme to produce active ingredients since its hydrolysate exhibitedthe best antioxidant activity among them and possessed large amount ofpotential active peptides.

Two purified proteins G-6 and G-4-2 were obtained from Arca subcrenata Lischke using the homogenization, salting-out with ammonium sulfate, ion-exchange chromatography and gel filtration chromatography techniques. The purity of G-6 and G-4-2 was over 96%, as measured by RP-HPLC. G-6 and G-4-2 were measured by SDS-PAGE and IEF-PAGE to have molecular weights of 8.2 kDa and 16.0 kDa, and isoelectric points of 6.6 and 6.1, respectively. The amino acid constituents of G-6 and G-4-2 were also determined. The existence of saccharides in G-6 was demonstrated by the phenol-sulfuric acid method. G-6 and G-4-2 inhibited the proliferation of human tumor cells in vitro. By MTT assay, the IC50 values of G-4-2 were 22.9 μg/mL, 46.1 μg/mL and 57.7 μg/mL against Hela, HL-60 and KB cell lines, respectively, and the IC50 value of G-6 against HL-60 cell line was measured to be 123.2 μg/mL.

Abstract The COVID-19 outbreak and associated lockdowns have heightened the challenges of social isolation in urban communities. Social interaction is recognized as a key factor in promoting people’s health, wellbeing, and social sustainability within urban communities. Public open spaces serve as a vital link between communities’ environment and individuals’ wellbeing. However, there has been limited research exploring how community parks impact residents’ social interaction in urban communities during the pandemic, particularly a lack of in-depth qualitative research in this area. To address this gap, this research investigated the impact of community parks on social interaction in master-planned communities in Sydney, using a qualitative case study method. A total of sixteen residents living in two selected communities—Breakfast Point and Liberty Grove—were interviewed during the COVID-19 pandemic in 2022. It was found that three themes and seven underlying subthemes of park-use factors influence residents’ social interactions: (1) quality of park spaces (rest spaces, BBQ/picnic recreation spaces, children’s playgrounds, sport facilities, and nature amenities), (2) pedestrian integration of parks (interconnected park network and well-dispersed small parks), and (3) pedestrian connectivity with surroundings. The findings provide theoretical, empirical, and practical implications for promoting social wellbeing and community sustainability in the post-COVID era.

Abstract Background Buffalo is a globally important livestock species, but its reproductive performance is relatively low than cattles. At present, dominant follicle development specific process and mechanistic role of follicular growth related genes in water buffaloes are not well understood. Therefore, we comprehensively performed transcriptomics of granulosa cells and oocytes from different-sized follicles in water buffalo to identify key candidate genes that influence follicle development and diameter, and further explored the potential regulatory mechanisms of granulosa cells and oocytes in the process of water buffalo follicle development. Results In this study, we found918 granulosa cell transcripts and 1401 oocyte transcripts were correlated in follicles of different diameters, and the expression differences were significant. Subsequent enrichment analysis of the co-expressed differentially expressed transcripts identified several genes targeted by long non-coding RNAs (lncRNAs) and associated with follicular development. Notably, the upregulation of BUB1 regulated by MSTRG.41325.4 and interactive action of SMAD2 and SMAD7 might have key regulatory role in follicular development. Additionally, we also detected key differentially expressed genes that potentially influence follicular hormone metabolism and growth, like ID2, CHRD, TGIF2 and MAD2L1, and constructed an interaction network between lncRNA transcripts and mRNAs. Conclusions In summary, this study preliminarily revealed the differences in gene expression patterns among buffalo follicles of different sizes and their potential molecular regulatory mechanisms. It provides a new perspective for exploring the mechanism of buffalo follicular dominance and improving buffalo reproductive performance.

Hyperparameters play a vital impact in the performance of most machine learning algorithms. It is a challenge for traditional methods to configure hyperparameters of the capsule network to obtain high-performance manually. Some swarm intelligence or evolutionary computation algorithms have been effectively employed to seek optimal hyperparameters as a combinatorial optimization problem. However, these algorithms are prone to get trapped in the local optimal solution as random search strategies are adopted. The inspiration for the hybrid rice optimization (HRO) algorithm is from the breeding technology of three-line hybrid rice in China, which has the advantages of easy implementation, less parameters and fast convergence. In the paper, genetic search is combined with the hybrid rice optimization algorithm (GHRO) and employed to obtain the optimal hyperparameter of the capsule network automatically, that is, a probability search technique and a hybridization strategy belong with the primary HRO. Thirteen benchmark functions are used to evaluate the performance of GHRO. Furthermore, the MNIST, Chest X-Ray (pneumonia), and Chest X-Ray (COVID-19 & pneumonia) datasets are also utilized to evaluate the capsule network learnt by GHRO. The experimental results show that GHRO is an effective method for optimizing the hyperparameters of the capsule network, which is able to boost the performance of the capsule network on image classification. [ABSTRACT FROM AUTHOR]

Foam fractionation is a green and economical primary separation technique and it has excellent application prospect in the field of food industry. However, it is difficult to simultaneously obtain the high values of enrichment ratio and recovery percentage in a batch operation of foam fractionation due to the opposite effects of operating parameters on interfacial adsorption and foam drainage. In order to solve this problem, multiple process intensification strategies of foam fractionation are developed. In this work, the current studies on the intensification methods of interfacial adsorption and foam drainage were firstly reviewed. The advantages and disadvantages of these methods are analyzed. Subsequently, the research progress of foam fractionation in the separation of proteins, enzymes, saponins, polyphenols and biological preservatives are summarized. Based on the literature review and problem analysis, three future research respects are proposed to promote the industrial application of foam fractionation: Developing new methods which would simultaneously improve interfacial adsorption and foam drainage, designing new collectors with strong binding specificity for non-surface-active materials and good reusability, and inhibiting protein denaturation during desorption process.

Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis, is a common metabolic liver disease worldwide. Currently, satisfactory drugs for NAFLD treatment remain lacking. Obesity and diabetes are the leading causes of NAFLD, and compounds with anti-obesity and anti-diabetic activities are considered suitable candidates for treating NAFLD. In this study, biochemical and histological assays revealed that a natural lignan schisanhenol (SAL) effectively decreased lipid accumulation and improved hepatic steatosis in free fatty acid (FFA)-treated HepG2 cells and high-fat diet (HFD)-induced NAFLD mice. Further, molecular analyses, microRNA (miRNA)-seq, and bioinformatics analyses revealed that SAL may improve NAFLD by targeting the miR-802/adenosine monophosphate-activated protein kinase (AMPK) pathway. Liver-specific overexpression of miR-802 in NAFLD mice significantly impaired SAL-mediated liver protection and decreased the protein levels of phosphorylated (p)-AMPK and PRKAB1. Dual-luciferase assay analysis further confirmed that miR-802 inhibits hepatic AMPK expression by binding to the 3' untranslated region of mouse Prkab1 or human PRKAA1. Additionally, genetic silencing of PRKAA1 blocked SAL-induced AMPK pathway activation in FFA-treated HepG2 cells. The results demonstrate that SAL is an effective drug candidate for treating NAFLD through regulating miR-802/AMPK-mediated lipid metabolism.

Abstract Background The effectiveness and safety of acupuncture therapy to delay lung function decline in chronic obstructive pulmonary disease (COPD) remain unclear. This study aimed to determine whether acupuncture, as an adjunctive therapy to COPD-guided medication, could prevent lung function decline. Methods This randomised, two-centre study was conducted between February 2022 and July 2023. Men and women aged 40–80 years with COPD were recruited. Participants received active or sham acupuncture three times a week (36 sessions total). The primary outcome was the change in the percentage of forced expiratory volume for 1 s to the predicted value (FEV1%) between the baseline and after the intervention. Results Overall, 238 participants were screened, and 74 (58 men [78.4%]; mean [standard deviation] age, 69.6 [7.2] years) were randomised into the acupuncture and sham acupuncture groups (37 per group). After the intervention, the change in FEV1% was 1.35 (95% confidence interval [CI]: -0.47 to 3.17) and -2.44 (95% CI: -4.56 to -0.33) in the acupuncture and sham acupuncture groups, respectively. The difference was -3.97 (95% CI: -6.2 to -1.74), and the adjusted difference was -3.46 (95% CI: -5.69 to -1.24, P = 0.003) between the groups. A significantly less decline was found in forced expiratory volume for 1 s in the acupuncture group. All treatment-related adverse events (acupuncture = 11, sham = 2) were mild. Conclusions Compared with sham acupuncture, acupuncture plus medication may delay lung function decline. However, further studies with a larger sample size and longer-term follow-up are needed to clarify the effects.

Abstract Soybean represents a vital source of premium plant-based proteins for human nutrition. Importantly, the level of water-soluble protein (WSP) is crucial for determining the overall quality and nutritional value of such crops. Enhancing WSP levels in soybean plants is a high-priority goal in crop improvement. This study aimed to elucidate the genetic basis of WSP content in soybean seeds by identifying quantitative trait loci (QTLs) and set the foundation for subsequent gene cloning and functional analysis. Using 180 F10 recombinant inbred lines generated by crossing the high-protein soybean cultivar JiDou 12 with the wild variety Ye 9, our researcher team mapped the QTLs influencing protein levels, integrating Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and gene expression profiling to identify candidate genes. During the 2020 and 2022 growing seasons, a standard bell-shaped distribution of protein content trait data was observed in these soybean lines. Eight QTLs affecting protein content were found across eight chromosomes, with LOD scores ranging from 2.59 to 7.30, explaining 4.15–11.74% of the phenotypic variance. Notably, two QTLs were newly discovered, one with a elite allele at qWSPC-15 from Ye 9. The major QTL, qWSPC-19, on chromosome 19 was stable across conditions and contained genes involved in nitrogen metabolism, amino acid biosynthesis, and signaling. Two genes from this QTL, Glyma.19G185700 and Glyma.19G186000, exhibited distinct expression patterns at maturity, highlighting the influence of these genes on protein content. This research revealed eight QTLs for WSP content in soybean seeds and proposed a gene for the key QTL qWSPC-19, laying groundwork for gene isolation and enhanced soybean breeding through the use of molecular markers. These insights are instrumental for developing protein-rich soybean cultivars.

Abstract Background The prevalence and severity of pediatric Mycoplasma pneumoniae pneumonia (MPP) poses a significant threat to the health and lives of children. In this study, we aim to systematically evaluate the value of routine blood parameters in predicting MPP and develop a robust and generalizable ensemble artificial intelligence (AI) model to assist in identifying patients with MPP. Methods We collected 27 features, including routine blood parameters and hs-CRP levels, from patients admitted to The Affiliated Dazu’s Hospital of Chongqing Medical University with or without MPP between January, 2023 and January, 2024. A classification model was built using seven machine learning (ML) algorithms to develop an integrated prediction tool for diagnosing MPP. It was evaluated on both an internal validation set (982 individuals) and an external validation set (195 individuals). The primary outcome measured the accuracy of the model in predicting MPP. Results The GBDT is state-of-the-art based on 27 features. Following inter-laboratory cohort testing, the GBDT demonstrated an AUC, accuracy, specificity, sensitivity, PPV, NPV, and F1-score of 0.980 (0.938–0.995), 0.928 (0.796–0.970), 0.929 (0.717-1.000), 0.926 (0.889–0.956), 0.922 (0.727-1.000), 0.937 (0.884–0.963), and 0.923 (0.800-0.966) in stratified 10-fold cross-validation. A GBDT-based AI Lab was developed to facilitate the healthcare providers in remote and impoverished areas. Conclusions The GBDT-based AI Lab tool, with high sensitivity and specificity, could help discriminate between pediatric MPP infection and non-MPP infection based on routine blood parameters. Moreover, a user-friendly webpage tool for AI Lab could facilitate healthcare providers in remote and impoverished areas where advanced technologies are not accessible.

Objectives: This meta-analysis aimed to explore the relationship between the dose of acupuncture sessions, acupuncture frequency, and acupuncture duration and its effects on migraine. Methods: Eight databases were searched for randomized controlled trials (RCTs) evaluating the efficacy of penetrating manual acupuncture for migraine published in English and Chinese from inception to June 20, 2024. The robust-error meta-regression (REMR) approach and non-linear meta-regression with restricted cubic spline (RCS) were used to investigate the dose-response association between acupuncture sessions, acupuncture frequency, and acupuncture duration and the frequency of migraine attacks. The potential nonlinear relationships was tested by restricting the regression coefficient to zero and a P value＜0.1. The statistical analysis was conducted using Stata 17.0. The risk of bias was independently assessed by two reviewers using the Cochrane tool. The reporting quality for acupuncture procedures was evaluated by STRICTA criteria. Results: Thirty-two RCTs involving 1562 participants were included, and the results showed a J-shaped dose-response association between acupuncture sessions, acupuncture frequency, and acupuncture duration and migraine attack frequency. After 16 acupuncture sessions, the change in the frequency of migraine attacks was 3.95 (95 %CI: 3.13 to 4.77). Three sessions of acupuncture a week resulted in a significant decrease in the frequency of migraine attacks, reaching 4.04 (95 % CI: 2.49 to 5.58). After two months of acupuncture, the frequency of migraine attacks decreased significantly, showing a difference of 4.05 (95 % CI: 3.61 to 4.49). Subsequently, the improvement trend gradually flattened, yielding diminishing benefits to patients. The risk of bias showed that seven studies were rated as “low risk”, two were rated as “high risk”, and the others were rated as “unclear risk”. The reporting quality of RCTs of acupuncture for migraine remain suboptimal. Conclusions: A non-linear dose-response relationship was found between acupuncture sessions, acupuncture frequency, and acupuncture duration and migraine attack frequency. The results of our study recommend 16 sessions of acupuncture with a frequency of 3 sessions/week and a treatment duration of 1.5 to 2 months. Registration number: This meta-analysis has been registered on PROSPERO (CRD42023400493).