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Hesperidin is a dihydroflavonoids, accounting for more than 50% of the total flavonoids in Citri Reticulatae Pericarpium (CRP) of traditional Chinese medicine. It is an effective antioxidant and free radical scavenger that has anti-inflammatory, antiviral and hypoglycemic properties. The latest studies reported that hesperidin has a potential for novel coronavirus resistance. However, little is known about the synthesis regulation and accumulation site of hesperidin in plants. In this study, hesperidin synthase gene Crc1,6RhaT was cloned, and the protein can be completely transformed flavanone-7-O-glucoside into hesperidin in vitro and in vivo. Studies on biological characteristics of ovary walls and exocarps showed that the relative expression levels of the Crc1,6RhaT gene and protein decreased gradually with the development of citrus fruits, and the relative content of hesperidin firstly increased, then sequentially decreased. In situ hybridization results further revealed that Crc1,6RhaT transcription was mainly concentrated in the secretory cavity cells, which are revealed to be the site of flavonoid synthesis. Immunocytochemistry localization results showed that the Crc1,6RhaT was mainly located in the endoplasmic reticulum, nucleus and vacuole of secretory cells. We inferred that the Crc1,6RhaT was synthesized in the endoplasmic reticulum, then was transported into the vacuoles through enlarged vesicles at the end of the endoplasmic reticulum. Our results not only revealed that Crc1,6RhaT may be involved in the synthesis of hesperidin of the main bioactive substance in the medicinal plant Citrus reticulata ‘Chachi’ fruit, but also provided novel insights into the main subcellular sites of hesperidin biosynthesis in vacuoles.

Abstract Hyperlipidemia and hypertension might play a role in cardiac fibrosis, in which a heterogeneous population of fibroblasts seems important. However, it is unknown whether CD34+ progenitor cells are involved in the pathogenesis of heart fibrosis. This study aimed to explore the mechanism of CD34+ cell differentiation in cardiac fibrosis during hyperlipidemia. Through the analysis of transcriptomes from 50,870 single cells extracted from mouse hearts and 76,851 single cells from human hearts, we have effectively demonstrated the evolving cellular landscape throughout cardiac fibrosis. Disturbances in lipid metabolism can accelerate the development of fibrosis. Through the integration of bone marrow transplantation models and lineage tracing, our study showed that hyperlipidemia can expedite the differentiation of non-bone marrow-derived CD34+ cells into fibroblasts, particularly FABP4+ fibroblasts, in response to angiotensin II. Interestingly, the partial depletion of CD34+ cells led to a notable reduction in triglycerides in the heart, mitigated fibrosis, and improved cardiac function. Furthermore, immunostaining of human heart tissue revealed colocalization of CD34+ cells and fibroblasts. Mechanistically, our investigation of single-cell RNA sequencing data through pseudotime analysis combined with in vitro cellular studies revealed the crucial role of the PPARγ/Akt/Gsk3β pathway in orchestrating the differentiation of CD34+ cells into FABP4+ fibroblasts. Through our study, we generated valuable insights into the cellular landscape of CD34+ cell-derived cells in the hypertrophic heart with hyperlipidemia, indicating that the differentiation of non-bone marrow-derived CD34+ cells into FABP4+ fibroblasts during this process accelerates lipid accumulation and promotes heart failure via the PPARγ/Akt/Gsk3β pathway.

Major depressive disorder (MDD) is a common mental illness. Currently, nearly 16% of the global population is affected by depression-related symptoms, while the diagnosis and treatment rate of MDD patients in China is only 9.5%. MDD is characterised by high morbidity and low recovery rate, and how to effectively improve its therapeutic effect has been a hot research topic in recent years. Antidepressants, as the main treatment for MDD, have the disadvantages of many adverse effects and slow onset of action, prompting people to pay attention to the non-pharmacological treatments of MDD. Dietary intervention is a kind of non-pharmacological treatment by changing dietary structures and rhythms; the current application of dietary intervention to psychiatry is very extensive, and it has been proved to be effective in the treatment of depression. Recent research suggests that dietary interventions can treat and ameliorate depressive symptoms by influencing brain-gut axis-related eating mechanisms. This article reviews the multidimensional exploration of dietary interventions in the treatment of depression: dietary structure interventions, dietary rhythm interventions, and the role of intestinal flora. It details the modalities of dietary interventions and the related mechanisms involved, and provides reference for dietary interventions in the treatment of depression-related symptoms.

The characteristic features of dissociative conversion disorder entail a partial or complete loss of normal integration in memory, identity awareness, immediate sensation, and motor control. This article documents a case of the disorder presenting with an onset of depressive mood, diminished interest, and facial tics, subsequently accompanied by intermittent fainting spells with limb convulsions. Despite multiple consultations in both general hospitals and psychiatric settings, and despite treatment with various antidepressants and antiepileptic medications, the patient's symptoms showed no significant improvement. The report of this case deepens the understanding of a complex and commonly misdiagnosed condition, offering valuable insights for the diagnosis and treatment of patients exhibiting similar symptoms.

Abstract Macrophages are multifunctional innate immune cells that play indispensable roles in homeostasis, tissue repair, and immune regulation. However, dysregulated activation of macrophages is implicated in the pathogenesis of various human disorders, making them a potential target for treatment. Through the expression of pattern recognition and scavenger receptors, macrophages exhibit selective uptake of pathogens and apoptotic cells. Consequently, the utilization of drug carriers that mimic pathogenic or apoptotic signals shows potential for targeted delivery to macrophages. In this study, a series of mannosylated or/and phosphatidylserine (PS) -presenting liposomes were developed to target macrophages via the design of experiment (DoE) strategy and the trial-and-error (TaE) approach. The optimal molar ratio for the liposome formulation was DOPC: DSPS: Chol: PEG-PE = 20:60:20:2 based on the results of cellular uptake and cytotoxicity evaluation on RAW 264.7 and THP-1 in vitro. Results from in vivo distribution showed that, in the DSS-induced colitis model and collagen II-induced rheumatoid arthritis model, PS-presenting liposomes (PS-Lipo) showed the highest accumulation in intestine and paws respectively, which holds promising potential for macrophage target therapy since macrophages are abundant at inflammatory sites and contribute to the progression of corresponding diseases. Organs such as the heart, liver, spleen, lung, and kidney did not exhibit histological alterations such as inflammation or necrosis when exposed to PC-presenting liposomes (PC-Lipo) or PS-Lipo. In addition, liposomes demonstrated hemobiocompatibility and no toxicity to liver or kidney for circulation and did not induce metabolic injury in the animals. Thus, the well-designed PS-Lipo demonstrated the most potential for macrophage target therapy.

Citrus Huanglongbing (HLB) is one of the most serious citrus diseases worldwide, causing huge economic losses every year and seriously affecting the development of the global citrus industry. In Lingnan region of China, HLB threatens the growth of important medicinal plants, such as Citrus reticulata 'Chachi', C. grandis 'Tomentosa', and C. medica 'Fingered'. Candidatus Liberibacter asiaticus (CLas) is the most common pathogen, which colonizes the phloem of plants and mainly infects rutaceae citrus species. At present, there is a lack of reports on the successful cultivation of CLas in vitro, making it difficult to study the pathogenic mechanism and control of the disease. Effector (also called effector protein) is a kind of pathogenic factor secreted by pathogens to the host, serving as an important weapon for pathogens to infect plants. The effectors are capable of targeting the key immune signal transduction and regulatory components of host cells, thereby inhibiting plant defense responses and enhancing the pathogenicity of pathogens. CLas can secrete over a hundred effectors, mainly divided into Secdependent effectors and non-classical secretory effectors according to different secretion pathways. Among them, there are 90 Sec-dependent effectors and 15 non-classical secretory effectors. They play a key role in the pathogenic process of infecting the host. Studies have shown that HLB effectors could target multiple cellular processes including plant immune signal transduction, autophagy, salicylic acid signaling pathway, and seriously disrupt the host's defense response to achieve colonization. Combined with recent researches on the pathogenic mechanism of HLB effectors, this article elaborates on the research overview of HLB and the classification of HLB effectors, and summarizes the pathogenic mechanism of effectors that affect citrus defense response. Finally, it offers a prospect on the future research directions, discusses the possibility of searching for important resistance genes to HLB based on identification of effector targets, with a aim to provide guidance for the pathogenic mechanism and disease control of HLB through the study of the effectors.

Abstract High intraocular pressure (IOP) is one of the early complications after pars plana vitrectomy (PPV), which may cause glaucoma and poor visual prognosis secondary to surgery. Proliferative vitreoretinopathy (PVR) is one of the complications of retinal detachment (RD) and is the main reason for the poor prognosis, which is related to different kinds of cytokines. It’s essential for the basic mechanism to analyze the relative aqueous humor cytokine profiles with IOP after PPV for RD. In this study, we have collected the aqueous humor of 16 patients and qualified 27 cytokines using Luminex and compared biomarkers with the high IOP group and the normal group. As a result, the concentrations of VEGF, IL-6, FGF2, and G-CSF upregulated significantly (P

Aberrant expression of cyclin-dependent kinase 5 (Cdk5) has been reported in pituitary adenomas. However, the role of Cdk5 in the tumorigenesis remains unclear. We show that prenatal p25-activated Cdk5 phosphorylates minichromosome maintenance protein 2 (Mcm2), enhancing minichromosome maintenance (MCM) family proteins and driving intermediate lobe-located melanotrope-originated pituitary tumorigenesis. In a mouse model with CaMKII promoter-driven transgenic induction of p25, we observed intermediate lobe-originated pituitary adenoma producing non-functional proopiomelanocortin (POMC)-derived peptides under persistent p25 overexpression. Single-cell RNA sequencing revealed Mcm2 may play an important role during tumor progression. Subsequently, Mcm2 was identified as a potential phosphorylated substrate of Cdk5, mediating the tumorous proliferation of melanotrope cells. Silencing Cdk5 or Mcm2 suppressed cell proliferation and colony formation in the 293T cell lines. Therefore, our findings provide a new mouse model of intermediate lobe-originated pituitary adenoma induced by p25/Cdk5 and unveil a previously unappreciated role of Cdk5 and Mcm2 in pituitary adenoma tumorigenesis.

Background The circadian variation pattern of sudden cardiac arrest (SCA) occurred in Chinese community including both community healthcare centres and primary hospitals remains unknown. This study analysed the circadian variation of SCA in the Chinese community.Methods Data between 2018 and 2022 from the remote ECG diagnosis system of Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine were analysed to examine the circadian rhythm of SCA, stratified by initial shockable (ventricular tachycardia or ventricular fibrillation) versus non-shockable (asystole or pulseless electrical activity) rhythm.Results Among 10 210 cases of SCA, major cases (8736, 85.6%) were non-shockable and 1474 (14.4%) cases were shockable. The circadian rhythm of SCA was as follows: peak time was from 08:00 to 11:59 (30.1%), while deep valley was from 00:00 to 03:59 (7.5%). The proportions of events by non-shockable and shockable events were similar and both reached their peak from 08:00 to 11:59, with a percentage of 29.0% and 36.4%, respectively. Multivariable analysis showed that the relative risk of shockable compared with non-shockable arrests was lower between 00:00 and 03:59 (adjusted OR (aOR): 0.72, 95% CI: 0.54 to 0.97, p=0.028) and 04:00 to 07:59 (aOR: 0.60, 95% CI: 0.46 to 0.79, p

IntroductionShort-video platforms have demonstrated vast potential for health education. To meet diverse user requirements, many short-video platforms have integrated livestreaming functionalities. This integration presents challenges for health content creators in formulating effective performance strategies, including decisions about which format to use (short video or livestream) and what type of content to produce. This study utilizes panel data from a prominent short-video platform in China to empirically investigate the impact of different forms and content characteristics on the performance of health content creators.MethodsWe conducted an empirical analysis using panel data obtained from a leading short-video platform in China. Our analysis focused on understanding how the behaviors associated with short videos and livestreaming impact the performance of health content creators. We examined form-level differences, analyzing the distinct roles of short video and livestreaming behaviors. Additionally, we explored content-level characteristics, investigating the effects of content coverage, health knowledge content, and advertising content on both short-term and long-term performance. The moderation effects of the creator’s occupation and certification type were also analyzed.ResultsOur form-level analysis revealed that health creators’ behaviors in short videos and livestreaming play distinct roles in their performance. Livestreaming behaviors resulted in short-term economic returns, while short video behaviors had a more significant effect on follow-ups, which are often viewed as long-term, more sustainable performance indicators. Content-level analysis showed that content coverage and health knowledge content enhance long-term performance but do not increase short-term performance. Conversely, advertising content was found to be essential for securing short-term financial income. The study also identified that the creator’s occupation and certification type moderate the impact of content on performance.ConclusionThis study integrates two media forms (short video and livestream), providing direct insights into the performance of health content creators in the realm of health education. Health content creators need to strategically balance their use of short videos and livestreaming to optimize both short-term and long-term performance outcomes. Specifically, increasing content coverage and health knowledge can enhance long-term engagement, while incorporating advertising content is crucial for immediate financial gains.

Abstract Citrus reticulata cv. Chachiensis (CRC) is an important medicinal plant, its dried mature peels named “Guangchenpi”, has been used as a traditional Chinese medicine to treat cough, indigestion, and lung diseases for several hundred years. However, the biosynthesis of the crucial natural products polymethoxylated flavonoids (PMFs) in CRC remains unclear. Here, we report a chromosome-scale genome assembly of CRC with the size of 314.96 Mb and a contig N50 of 16.22 Mb. Using multi-omics resources, we discover a putative caffeic acid O-methyltransferase (CcOMT1) that can transfer a methyl group to the 3-hydroxyl of natsudaidain to form 3,5,6,7,8,3’,4’-heptamethoxyflavone (HPMF). Based on transient overexpression and virus-induced gene silencing experiments, we propose that CcOMT1 is a candidate enzyme in HPMF biosynthesis. In addition, a potential gene regulatory network associated with PMF biosynthesis is identified. This study provides insights into PMF biosynthesis and may assist future research on mining genes for the biosynthesis of plant-based medicines.

Abstract Background The plastid is the photosynthetic organelle in plant cell, and the plastid genomes (plastomes) are generally conserved in evolution. As one of the most economically and ecologically important order of angiosperms, Poales was previously documented to exhibit great plastomic variation as an order of photoautotrophic plants. Results We acquired 93 plastomes, representing all the 16 families and 5 major clades of Poales to reveal the extent of their variation and evolutionary pattern. Extensive variation including the largest one in monocots with 225,293 bp in size, heterogeneous GC content, and a wide variety of gene duplication and loss were revealed. Moreover, rare occurrences of three inverted repeat (IR) copies in angiosperms and one IR loss were observed, accompanied by short IR (sIR) and small direct repeat (DR). Widespread structural heteroplasmy, diversified inversions, and unusual genomic rearrangements all appeared in Poales, occasionally within a single species. Extensive repeats in the plastomes were found to be positively correlated with the observed inversions and rearrangements. The variation all showed a “small-large-moderate” trend along the evolution of Poales, as well as for the sequence substitution rate. Finally, we found some positively selected genes, mainly in C4 lineages, while the closely related lineages of those experiencing gene loss tended to have undergone more relaxed purifying selection. Conclusions The variation of plastomes in Poales may be related to its successful diversification into diverse habitats and multiple photosynthetic pathway transitions. Our order-scale analyses revealed unusual evolutionary scenarios for plastomes in the photoautotrophic order of Poales and provided new insights into the plastome evolution in angiosperms as a whole.

Sea urchins produced by aquaculture could enhance declining wild populations and provide a sufficient roe product to satisfy increasing market demand. This study reports a method for large-scale rearing of the edible tropical sea urchin Salmacis sphaeroides, from induction of larval metamorphosis and settlement, to juvenile rearing and grow-out. Larvae were reared in 500-L hatchery tanks, on a diet of the microalga Chaetoceros muelleri at concentrations ranging from 2500 to 24,000 cells mL−1, with daily water renewal of one-third to two-thirds of the volume depending on their developmental stage. The larvae breeding protocol proved suitable for this species, and competent larvae occurred at 12 days post-fertilization. To induce metamorphosis, we tested exposure to potassium chloride (KCl) at different concentrations (0, 25, 50, 100, 200, and 400 mmol L−1) and for different durations (5, 10, and 20 min). Exposure to 200 mmol L−1 KCl for 5 min resulted in the highest proportion of metamorphosed individuals (41.67 ± 2.89 %). Using this method, the densities of juveniles attaching to settlement plates (232.50 ± 41.23 ind. per plate; settlement percentage ca. 3.88 ± 0.69 %) were approximately twice as high as those of the controls (105.75 ± 15.52 ind. per plate; settlement percentage ca. 1.76 ± 0.26 %). Next, two batches of juveniles were grown out in sea cages. In the first batch (deployed for ca. 4 months), the absolute growth rate of the test diameter (AGRD) was 12.79 ± 0.98 mm month−1 from May to September; in the second batch (deployed for 6 months), the AGRD was 5.68 ± 0.90 mm month−1 from October to May of the following year. Survival of the juvenile S. sphaeroides in the sea cages was high (86.56 %–100 %). Finally, the S. sphaeroides cultivated in the second batch were harvested (at a mean test diameter of 71.24 ± 1.45 mm, and wet weight of 101.24 ± 1.91 g) on May 28 of the second year; all animals had matured and could be successfully utilized as broodstock. The fatty acid composition of the gonads was then compared between cultivated and wild-collected adult S. sphaeroides. The proportion of polyunsaturated fatty acids in the cultivated sea urchins (16.59 ± 0.67 %) exceeded that in wild-collected individuals (13.13 ± 0.42 %). From these experiments we conclude that S. sphaeroides is a sea urchin species with excellent potential for aquaculture; the present methods and data will provide helpful information for their mass production in South China.

This qualitative study sought to explore how women entrepreneurs leverage the Internet to empower their entrepreneurial activities in the Chinese context. To this end, we first conducted semi-structured interviews with 30 women entrepreneurs, and then analyzed their transcripts by following the principles of thematic analysis from grounded theory method. After the three-phase coding procedure, we developed a conceptual model of Internet use of women entrepreneurs which were composed of Internet marketing, Internet purchasing, and Internet learning. The current study provides the first evidence for the multidimensional construct of Internet use with a sample of women entrepreneurs in China. A hypothesis concerning the relationship between Internet use and women entrepreneurial performance is proposed for future investigation. Implications for women entrepreneurs and policymakers are discussed.

The gut microbiome plays important roles in metabolic and immune system related to the health of host. This study applied non-invasive sampling and 16S rDNA high-throughput sequencing to study the gut microbiota structure of red pandas (Ailurus fulgens) for the first time under different geographical latitudes in captivity. The results showed that the two predominant phyla Firmicutes (59.30%) and Proteobacteria (38.58%) constituted 97.88% of the total microbiota in all the fecal samples from north group (red pandas from Tianjin Zoo and Jinan Zoo) and south group (red pandas from Nanjing Hongshan Forest Zoo). The relative abundance of Cyanobacteria in north group was significantly higher than that in south group. At the genus level, Escherichia-Shigella (24.82%) and Clostridium_sensu_stricto_1 (23.00%) were common dominant genera. The relative abundance of norank_f__norank_o__Chloroplast, Terrisporobacter and Anaeroplasma from south group was significantly higher than that of north group. Alpha and Beta analysis consistently showed significant differences between north group and south group, however, the main functions of intestinal microbiota were basically the same, which play an important role in metabolic pathways, biosynthesis of secondary metabolites, microbial metabolism in different environments, and amino acid biosynthesis. The variations in gut microbiota between the northern and southern populations of the same species, both kept in captivity, which are primarily driven by significant differences in climate and diet. These findings provide a deeper understanding of the gut microbiota in red pandas and have important implications for their conservation, particularly in optimizing diet and environmental conditions in captivity.

In this study, the role of matrine, a component derived from traditional Chinese medicine, in modulating macrophage polarization and its effects on traumatic heterotopic ossification (HO) in mice was investigated. Traumatic HO is a pathological condition characterized by abnormal bone formation in nonskeletal tissues, often following severe trauma or surgery. The mechanisms underlying HO involve an enhanced inflammatory response and abnormal bone formation, with macrophages playing a crucial role. Our study demonstrated that matrine effectively inhibits the polarization of bone marrow-derived macrophages (BMDMs) toward the M2 phenotype, a subtype associated with anti-inflammatory processes and implicated in the progression of HO. Using in vitro assays, we showed that matrine suppresses key M2 markers and inhibits the MAPK signaling pathway in BMDMs. Furthermore, in vivo experiments revealed that matrine treatment significantly reduced HO formation in the Achilles tendons of mice and downregulated the expression of markers associated with M2 macrophages and the MAPK pathway. Our findings suggest that the ability of matrine to modulate macrophage polarization and inhibit the MAPK pathway has therapeutic potential for treating traumatic HO, providing a novel approach to managing this complex condition.

Immunopeptides have low toxicity, low immunogenicity and targeting, and broad application prospects in drug delivery and assembly, which are diverse in application strategies and drug combinations. Immunopeptides are particularly important for regulating ocular immune homeostasis, as the eye is an immune-privileged organ. Immunopeptides have advantages in adaptive immunity and innate immunity, treating eye immune-related diseases by regulating T cells, B cells, immune checkpoints, and cytokines. This article summarizes the application strategies of immunopeptides in innate immunity and adaptive immunity, including autoimmunity, infection, vaccine strategies, and tumors. Furthermore, it focuses on the mechanisms of immunopeptides in mediating ocular immunity (autoimmune diseases, inflammatory storms, and tumors). Moreover, it reviews immunopeptides’ application strategies and the therapeutic potential of immunopeptides in the eye. We expect the immune peptide to get attention in treating eye diseases and to provide a direction for eye disease immune peptide research.

Abstract The emergence of various topological semimetal states presents a novel opportunity for enhancing the efficiency of thermoelectric transport. This study introduces a recipe to improve the thermoelectric (TE) performance in topological materials containing single‐pair Weyl points (SP WPs) fermions and phonons. The recipe focuses on two key factors contributing to the enhancement of TE performance: the increase in the density of states to achieve a high power factor, and the introduction of additional phonon scattering to reduce the lattice thermal conductivity. The proposed recipe is confirmed in a half‐metallic SP WPs material BaNiIO6 through first‐principles methods. An enhanced density of states arises near the energy of the SP WPs in BaNiIO6, leading to a peak power factor connected to the complex Fermi surface due to the degeneracy of Weyl pockets in energy. Furthermore, it is shown that the SP WPs phonons in BaNiIO6 possess a high scattering rate and can likely contribute to the low lattice thermal conductivity, especially when two crossing points in SP WPs do not degenerate in frequency. The new recipe can be used for discovering high‐performance thermoelectric materials in the future by utilizing the transport advantages of degenerate‐in‐energy SP WPs fermions and non‐degenerate‐in‐frequency SP WPs phonons.

BackgroundObservational studies have indicated that immune dysregulation in primary sclerosing cholangitis (PSC) primarily involves intestinal-derived immune cells. However, the causal relationship between peripheral blood immune cells and PSC remains insufficiently understood.MethodsA bidirectional two-sample Mendelian randomization (MR) analysis was implemented to determine the causal effect between PBC and 731 immune cells. All datasets were extracted from a publicly available genetic database. The standard inverse variance weighted (IVW) method was selected as the main method for the causality analysis. Cochran’s Q statistics and MR-Egger intercept were performed to evaluate heterogeneity and pleiotropy.ResultsIn forward MR analysis, the expression ratios of CD11c on CD62L+ myeloid DC (OR = 1.136, 95% CI = 1.032–1.250, p = 0.009) and CD62L-myeloid DC AC (OR = 1.267, 95% CI = 1.086–1.477, p = 0.003) were correlated with a higher risk of PSC. Each one standard deviation increase of CD28 on resting regulatory T cells (Treg) (OR = 0.724, 95% CI = 0.630–0.833, p < 0.001) and CD3 on secreting Treg (OR = 0.893, 95% CI = 0.823–0.969, p = 0.007) negatively associated with the risk of PSC. In reverse MR analysis, PSC was identified with a genetic causal effect on EM CD8+ T cell AC, CD8+ T cell AC, CD28− CD127− CD25++ CD8+ T cell AC, CD28− CD25++ CD8+ T cell AC, CD28− CD8+ T cell/CD8+ T cell, CD28− CD8+ T cell AC, and CD45 RA− CD28− CD8+ T cell AC.ConclusionOur study indicated the evidence of causal effects between PSC and immune cells, which may provide a potential foundation for future diagnosis and treatment of PSC.

Chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer (CRC). Cisplatin (DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeutic drug effects which are characterized by the activation of slow-cycle programs and DNA repair. Among the elements that lead to DDP resistance, O6-methylguanine (O6-MG)-DNA-methyltransferase (MGMT), a DNA-repair enzyme, performs a quintessential role. In this study, we clarify the significant involvement of MGMT in conferring DDP resistance in CRC, elucidating the underlying mechanism of the regulatory actions of MGMT. A notable upregulation of MGMT in DDP-resistant cancer cells was found in our study, and MGMT repression amplifies the sensitivity of these cells to DDP treatment in vitro and in vivo. Conversely, in cancer cells, MGMT overexpression abolishes their sensitivity to DDP treatment. Mechanistically, the interaction between MGMT and cyclin dependent kinase 1 (CDK1) inducing slow-cycling cells is attainted via the promotion of ubiquitination degradation of CDK1. Meanwhile, to achieve nonhomologous end joining, MGMT interacts with XRCC6 to resist chemotherapy drugs. Our transcriptome data from samples of 88 patients with CRC suggest that MGMT expression is co-related with the Wnt signaling pathway activation, and several Wnt inhibitors can repress drug-resistant cells. In summary, our results point out that MGMT is a potential therapeutic target and predictive marker of chemoresistance in CRC.

Summary: This review explores the hallmarks of cancer resistance, including drug efflux mediated by ATP-binding cassette (ABC) transporters, metabolic reprogramming characterized by the Warburg effect, and the dynamic interplay between cancer cells and mitochondria. The role of cancer stem cells (CSCs) in treatment resistance and the regulatory influence of non-coding RNAs, such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are studied. The chapter emphasizes future directions, encompassing advancements in immunotherapy, strategies to counter adaptive resistance, integration of artificial intelligence for predictive modeling, and the identification of biomarkers for personalized treatment. The comprehensive exploration of these hallmarks provides a foundation for innovative therapeutic approaches, aiming to navigate the complex landscape of cancer resistance and enhance patient outcomes.

The aim of this research was to examine the correlation between the exposure to bisphenol analogues (BPs), such as bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS), and the risk of developing systemic lupus erythematosus (SLE). Ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was utilized to measure the levels of BPA, BPF, and BPS in the urine of 168 female participants diagnosed with SLE and 175 female participants who were deemed healthy controls. Logistic regression models were utilized to assess the connections between levels of bisphenol and the risk of SLE. The findings indicated that levels of BPA and BPF in the urine of individuals with SLE were markedly elevated compared to those in the control group. Higher exposure to BPA and BPF exhibited positive dose-response relationships with increased SLE risk. No significant associations were identified between BPS and the risk of SLE. These findings suggest exposure to BPA and BPF may be implicated as novel environmental triggers in the development of autoimmunity such as SLE. The significantly increased levels of these bisphenol analogues detected in SLE patients versus healthy controls, along with the associations between higher exposures and elevated SLE risk, which offers crucial hints for comprehending how endocrine-disrupting substances contribute to the genesis of autoimmune illnesses. Further research using robust longitudinal assessments of bisphenol analogue exposures is warranted to corroborate these epidemiological findings. Overall, this study highlights potential environmental risk factors for SLE while calling for additional investigation into the impact of bisphenol exposures on autoimmunity development.

Medicinal plants contain numerous bioactive secondary metabolites (SMs) that can be used for the treatment and prevention of diseases. SM concentration is a crucial standard for evaluating the quality of medicinal plants. SM accumulation is affected by multiple factors, including genetic background, climate, soil physical and chemical properties, and environmental changes. In recent years, increasing studies have indicated that rhizospheric and endophytic microorganisms, play an essential role in regulating the accumulation of SMs in medicinal plants. While some microorganisms establish symbiotic relationships with medicinal plants to promote plant growth. Other microorganisms can directly synthesize SMs or promote plant SM biosynthesis through multiple strategies, such as activating plant immune signaling pathways and secreting plant hormones into host cells to manipulate hormone-mediated pathways. In contrast, SMs may improve plant resistance to environmental stresses, thereby affecting the composition of rhizospheric and endophytic microorganisms. In this review, we summarized the recent progress in understanding the role of microorganisms in regulating SM accumulation in medicinal plants. Further studies should focus on the application of utilizing microorganisms to enhance the accumulation of bioactive SMs in medicinal plants.

Abstract Breast cancer (BC) is a multifaceted disease characterized by distinct molecular subtypes and varying responses to treatment. In BC, the phosphatidylinositol 3-kinase (PI3K) pathway has emerged as a crucial contributor to the development, advancement, and resistance to treatment. This review article explores the implications of the PI3K pathway in predictive, preventive, and personalized medicine for BC. It emphasizes the identification of predictive biomarkers, such as PIK3CA mutations, and the utility of molecular profiling in guiding treatment decisions. The review also discusses the potential of targeting the PI3K pathway for preventive strategies and the customization of therapy based on tumor stage, molecular subtypes, and genetic alterations. Overcoming resistance to PI3K inhibitors and exploring combination therapies are addressed as important considerations. While this field holds promise in improving patient outcomes, further research and clinical trials are needed to validate these approaches and translate them into clinical practice. Graphical Abstract

Abstract Many types of tumors feature aerobic glycolysis for meeting their increased energetic and biosynthetic demands. However, it remains still unclear how this glycolytic phenomenon is achieved and coordinated with other metabolic pathways in tumor cells in response to growth stimuli. Here we report that activation of AKT1 induces a metabolic switch to glycolysis from the mitochondrial metabolism via phosphorylation of cytoplasmic malic enzyme 2 (ME2), named ME2fl (fl means full length), favoring an enhanced glycolytic phenotype. Mechanistically, in the cytoplasm, AKT1 phosphorylates ME2fl at serine 9 in the mitochondrial localization signal peptide at the N-terminus, preventing its mitochondrial translocation. Unlike mitochondrial ME2, which accounts for adjusting the tricarboxylic acid (TCA) cycle, ME2fl functions as a scaffold that brings together the key glycolytic enzymes phosphofructokinase (PFKL), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and pyruvate kinase M2 (PKM2), as well as Lactate dehydrogenase A (LDHA), to promote glycolysis in the cytosol. Thus, through phosphorylation of ME2fl, AKT1 enhances the glycolytic capacity of tumor cells in vitro and in vivo, revealing an unexpected role for subcellular translocation switching of ME2 mediated by AKT1 in the metabolic adaptation of tumor cells to growth stimuli.

Abstract This paper explores the feasibility and principle of hepatic parenteral fluorescence imaging technology after retrograde injection of indocyanine green (ICG) through endoscopic nasobiliary drainage (ENBD). The data were collected from 53 patients with cholecystolithiasis and choledocholithiasis, from October 2022 to March 2023, diagnosed by fluorescence imaging technique retrograde biliary approach (FIT-RB). We divided the patients into two groups according to the features of liver parenchyma, the poor group (n = 34, including scattered or no imaging) and the good group (n = 19, regular uniform imaging). We compared and analyzed the perioperative results of the two groups and explored the influencing factors of the success of FIT-RB and the ICG concentration suitable for this imaging technique. The good imaging rate of the 53 enrolled cases was 35.8%. The bilirubin level before ENBD and laparoscopic cholecystectomy in the poor group was significantly higher than that in the good group (P

Abstract Objective To create an automated machine learning model using sacroiliac joint MRI imaging for early sacroiliac arthritis detection, aiming to enhance diagnostic accuracy. Methods We conducted a retrospective analysis involving 71 patients with early sacroiliac arthritis and 85 patients with normal sacroiliac joint MRI scans. Transverse T1WI and T2WI sequences were collected and subjected to radiomics analysis by two physicians. Patients were randomly divided into training and test groups at a 7:3 ratio. Initially, we extracted the region of interest on the sacroiliac joint surface using ITK-SNAP 3.6.0 software and extracted radiomic features. We retained features with an Intraclass Correlation Coefficient > 0.80, followed by filtering using max-relevance and min-redundancy (mRMR) and LASSO algorithms to establish an automatic identification model for sacroiliac joint surface injury. Receiver operating characteristic (ROC) curves were plotted, and the area under the ROC curve (AUC) was calculated. Model performance was assessed by accuracy, sensitivity, and specificity. Results We evaluated model performance, achieving an AUC of 0.943 for the SVM-T1WI training group, with accuracy, sensitivity, and specificity values of 0.878, 0.836, and 0.943, respectively. The SVM-T1WI test group exhibited an AUC of 0.875, with corresponding accuracy, sensitivity, and specificity values of 0.909, 0.929, and 0.875, respectively. For the SVM-T2WI training group, the AUC was 0.975, with accuracy, sensitivity, and specificity values of 0.933, 0.889, and 0.750. The SVM-T2WI test group produced an AUC of 0.902, with accuracy, sensitivity, and specificity values of 0.864, 0.889, and 0.800. In the SVM-bimodal training group, we achieved an AUC of 0.974, with accuracy, sensitivity, and specificity values of 0.921, 0.889, and 0.971, respectively. The SVM-bimodal test group exhibited an AUC of 0.964, with accuracy, sensitivity, and specificity values of 0.955, 1.000, and 0.875, respectively. Conclusion The radiomics-based detection model demonstrates excellent automatic identification performance for early sacroiliitis.

BackgroundThe etiopathogenesis of major depressive disorder （MDD） is strongly associated with neuroinflammation. MDD is a highly heterogeneous psychiatric disorder， and the disease subtyping is an essential step for the identification of biological markers. The presence of psychomotor retardation seriously affects the prognosis of MDD， whereas the underlying mechanism is not yet completely clear. A potential involvement of granulocyte colony-stimulating factor （G-CSF） and macrophage colony-stimulating factor （M-CSF） in the pathogenesis of MDD with psychomotor retardation has been suggested in previous studies， but little detailed research has been completed.ObjectiveTo analyze the correlation of plasma G-CSF and M-CSF levels with psychomotor retardation in patients with MDD， and to explore the potential biological underpinnings of psychomotor retardation in MDD.MethodsA total of 50 MDD patients who met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） and attended the outpatient clinics of Shanghai Mental Health Center from April 2018 to April 2019 were included. The severity of symptoms was assessed using the Hamilton Depression Scale-17 item （HAMD-17）. According to the retardation factor in HAMD-17， patients with a score of ≥8 were included in retardation group （n=22）， and those with a score below 8 were included in non-retardation group （n=28）. Another 22 age- and sex-matched healthy controls were concurrently recruited. Plasma G-CSF and M-CSF levels were measured in all subjects using Luminex liquid suspension chip technology. Spearman correlation analysis was adopted to verify the correlation of retardation factor score in HAMD-17 with plasma G-CSF and M-CSF levels in MDD patients.ResultsPlasma G-CSF levels were decreased in MDD patients compared with healthy controls ［57.34（39.24， 83.15）pg/mL vs. 71.47（61.20， 79.99）pg/mL， Z=-2.098， P

Background: Natural killer (NK) cells play a role in the pathogenesis of various metabolic diseases related to obesity. While our initial findings have indicated a potential involvement of NK cells in the pathogenesis of type 2 diabetes mellitus, the precise mechanism underlying NK cell-mediated development of this form of diabetes remains inadequately comprehended.Objective: To investigate the impact and the underlying mechanism of high glucose and elevated levels of free fatty acids (FFAs) on immune and inflammatory responses and oxidative stress in NK92 cells.Methods: In this experiment, the CCK8 cytotoxicity assay was used to select the 44.4 mM and 1.5 mM concentrations of high glucose and high FFAs, respectively, to treat NK92 cells for 4 days. The concentrations of superoxide dismutase (SOD) and glutathione (GSH) were determined using a biochemical analyzer. Intracellular reactive oxygen species (ROS) levels, cytokines concentrations (TNF-α, IFN-γ, IL-6, and IL-10), and the expression levels of intracellular molecules (perforin and granzyme B) were assessed by flow cytometry.Results: The number of NK92 cell clumps was significantly reduced in the high-FFA (HF) group. In addition, the production of ROS and levels of cytokines (TNF-α, IFN-γ, IL-6, and IL-10) significantly decreased in the HF group but showed no significant change in the high-glucose (HG) group. This observation was consistent with the expression levels of perforin and granzyme B that decreased in the HF group.Conclusion: High FFAs induced morphological changes and serious damage to oxidative stress and inflammatory response in NK92 cells.

Abstract. Background:. Red-cell transfusion is critical for surgery during the peri-operative period; however, the transfusion threshold remains controversial mainly owing to the diversity among patients. The patient's medical status should be evaluated before making a transfusion decision. Herein, we developed an individualized transfusion strategy using the West-China-Liu's Score based on the physiology of oxygen delivery/consumption balance and designed an open-label, multicenter, randomized clinical trial to verify whether it reduced red cell requirement as compared with that associated with restrictive and liberal strategies safely and effectively, providing valid evidence for peri-operative transfusion. Methods:. Patients aged >14 years undergoing elective non-cardiac surgery with estimated blood loss > 1000 mL or 20% blood volume and hemoglobin concentration

Green stormwater infrastructure (GSI) is increasingly implemented worldwide to address stormwater issues while providing co-benefits such as habitat provision. However, research on public perceptions of GSI’s ecosystem benefits is limited, and barriers such as perception and maintenance hinder biodiversity promotion in GSI. Through an online survey (n = 781), we explored how residents in four Northeast US urban areas—Prince George’s County and Montgomery County, MD, New York City, and Philadelphia, PA—perceived the benefits and concerns regarding two types of bioswales (biodiverse and turf). Biodiverse swales feature various plants to promote biodiversity, whereas turf swales are primarily grass-covered. Our analyses included paired-samples t-tests, independent t-tests, one-way repeated measures ANOVA tests, and one-way ANOVA tests to compare perceptions across bioswale types, aspects of benefit/concern, and locations. Both bioswale types were recognized for enhancing green spaces and neighborhood aesthetics. Residents perceived greater environmental and social benefits from biodiverse swales than turf swales, particularly for habitat provision. While overall concerns for both bioswale types were low, potential issues like pest cultivation and the unappealing appearance of biodiverse swales remain significant barriers. Notably, implementing biodiverse swales alleviated initial concerns, especially about pests, suggesting familiarity can enhance acceptance. Location-specific differences in perception were observed, with New York City showing higher perceived benefits and concerns and Montgomery County exhibiting the lowest concerns. This variance is likely due to distinct urban environments, levels of environmental awareness, and demographic profiles.

Photovoltaic (PV) power generation is highly stochastic and intermittent, which poses a challenge to the planning and operation of existing power systems. To enhance the accuracy of PV power prediction and ensure the safe operation of the power system, a novel approach based on seasonal division and a periodic attention mechanism (PAM) for PV power prediction is proposed. First, the dataset is divided into three components of trend, period, and residual under fuzzy c-means clustering (FCM) and the seasonal decomposition (SD) method according to four seasons. Three independent bidirectional long short-term memory (BiLTSM) networks are constructed for these subsequences. Then, the network is optimized using the improved Newton–Raphson genetic algorithm (NRGA), and the innovative PAM is added to focus on the periodic characteristics of the data. Finally, the results of each component are summarized to obtain the final prediction results. A case study of the Australian DKASC Alice Spring PV power plant dataset demonstrates the performance of the proposed approach. Compared with other paper models, the MAE, RMSE, and MAPE performance evaluation indexes show that the proposed approach has excellent performance in predicting output power accuracy and stability.

In this study, volatile compounds from Cinnamomum cassia Presl. leaves from different regions of China were identified using gas chromatography coupled with mass spectrometry (GC-MS) and Fourier-transform infrared (FTIR) spectroscopy combined with chemometrics. The results showed that the essential oil yields greatly varied across regions, with the density of oil cells at the accumulation and saturation stages playing a key role in this yield. GC-MS analysis revealed a higher content of trans-cinnamaldehyde in samples from the Xijiang River basin (No. 1-8) than in those from Baise Guangxi (No. 9). Variable importance in projection analysis identified five differential marker components for assessing the geographical origin of C. cassia leaves: trans-cinnamaldehyde, acetophenone, cis-cinnamaldehyde, camphor, and α-thujene. Hierarchical cluster analysis, similarity evaluation, and principal component analysis from FTIR fingerprinting indicated that essential oil compositions of samples No. 1-6 from the Xijiang River basin were closely related. In contrast, the Baise sample (Western Guangxi) significantly differed from the other eight, likely due to the geographical distance. Our results indicate that the methods employed are effective for determining the geographical distribution and assessing the quality of raw cinnamon in herbal medicine.

Women have become an increasingly important force in entrepreneurship, and their relatively low entrepreneurial competence has aroused widespread attention from the academia. Drawing from the resource-based theory and the social support theory, this study aims to explore the impact of Internet use on women’s entrepreneurial competence and the roles of entrepreneurial resource acquisition and family support in this relationship. After collecting a sample of 328 women entrepreneurs in China, this study demonstrates that Internet use is positively related to women’s entrepreneurial competence, and this relation is partially mediated by entrepreneurial resource acquisition. Moreover, family support moderates the relation between Internet use and entrepreneurial resource acquisition as well as the mediating effect of entrepreneurial resource acquisition. The results of the current study contribute to revealing how Internet use affects women’s entrepreneurial competence, including its direct and indirect effects and boundary conditions. Practical implications for policy-makers and female entrepreneurs are also provided.

Increasing demands for livestock products have stimulated rapid increases in the number of livestock and the scale of farming, thus increasing pressure on resources and the environment. Coordinating the development of livestock production (LP) with residential consumption (RC), resources and the environmental carrying capacity (RECC) is important to ensure sustainable development. In this study, the entropy weight method and the improved-coupling coordination degree (CCD) model were used to identify the spatial–temporal coordination development characteristics of livestock production-residential consumption-resource and environmental carrying capacity (LRRE). Furthermore, the spatial autocorrelation model (SAM) and gray model (GM) were used to analyze the spatial aggregation characteristics and future development trends of the CCDs of the LRRE in China. The findings show that the CCDs of the LRRE values in 31 Chinese provinces increased from 2005 to 2020, but no provinces reached a high coordination level. Specifically, the coordinated development level of LRRE is relatively high in the central, eastern and northeastern regions and relatively low in the western region. The spatial autocorrelation analysis confirmed that the high-high (H-H) aggregation areas were mainly distributed in the northeastern, eastern, and central regions, while low-high (L-H) agglomeration was distributed in the western region. This phenomenon is mainly attributed to the continuous expansion of the scale of livestock production in western China. Regions with relatively developed economies have more funds to invest in environmental protection projects. Using GM method, we find that the CCDs of LRRE in 31 provinces in China will increase from 2021 to 2030, and all provinces will reach the basic coordination level. However, most of the western regions will barely reach the basic coordination level. This result indicates that the low level of LRRE development in western China may be difficult to change in the short term. The level of coordinated LRRE development in the relatively developed eastern region is increasing. The spatial layout of China’s livestock industry should be appropriately adjusted, its expansion rate in the western region should be decreased, and the ecological environment of the areas bordering the western and central regions should be improved. These findings have practical implications for other large livestock production countries. Promoting the coordinated development of LRRE is also an important condition for agricultural transformation in developing countries, especially for improving the environment in key areas of the livestock industry.

IntroductionNucleic acid-sensing (NAS) pathways could induce innate and adaptive immune responses. However, rare evidence exhibited how the core genes of the NAS pathways affected the immune response and prognosis of small cell lung cancer (SCLC) patients.MethodsWe conducted a comprehensive bioinformatic analysis based on the RNA profiles of 114 SCLC patients, including 79 from cBioPortal, 21 from GSE30219, and 14 from our sequencing data. The multiplex immunohistochemistry (mIHC) was used to characterize the role of NAS related genes in the tumor microenvironment (TME) of SCLC.ResultsA prognostic model (7NAS risk model) was constructed based on 7 NAS-related genes which was demonstrated as an independent prognostic index. The low-risk group was identified to have a better prognosis and an immune-activated microenvironment in both the public datasets and our dataset. Intriguingly, mIHC data showed that CD45+ immune cells, CD8+ T lymphocytes, and CD68+ macrophages were prevalently enriched in low-risk SCLC patients and positively correlated with IRF1 expression. Additionally, Patients in the low-risk group might have superior responses to chemotherapy and immunotherapy.ConclusionConclusively, this study created a new risk model based on genes associated with NAS pathways which could predict the prognosis and response of treatment in patients with SCLC.

Delayed luminescence (DL) refers to the photon-induced ultra-weak luminescence emitted by samples after the light source is switched off. As a noninvasive method for health monitoring and disease diagnosis, DL has attracted increasing attention. The further development of this technology is valuable for the study of complex biological processes, such as different growth stages. If such studies were to be conducted in humans, large numbers of subjects of all ages would need to be recruited, and individual differences would be inevitable. The budding yeast Saccharomyces cerevisiae (S. cerevisiae) has a short population lifespan, and the growth phases can be monitored within dozens of hours. Therefore, S. cerevisiae is an ideal model organism for research. In this study, we investigated the physiological characteristics and DL emission of S. cerevisiae during growth in glucose-based media and entry into stationary phase, and the results showed that DL kinetic curves of yeast cells in the growing phase were obviously separated from those of stationary phase cells. Moreover, the metabolic and physiological characteristics of the yeast cell population were discussed using the DL emission parameters I0, τ and γ. We also discussed the possibility of assessing entropy using DL emission parameters. Our research demonstrates the potential of this technology to be used in wider applications.

The fecal microbiota plays an important role in maintaining animal health and is closely related to host life activities. In recent years, there have been an increasing number of studies on the fecal microbiota from birds. An exploration of the effects of species and living environments on the composition of gut microbiota will provide better protection for wildlife. In this study, non-injury sampling and 16S rDNA high-throughput sequencing were used to investigate the bacterial composition and diversity of the fecal microbiota in silver pheasants (Lophura nycthemera) and golden pheasants (Chrysolophus pictus) from Tianjin Zoo and Beijing Wildlife Park. The results showed that the abundance of Firmicutes was the highest in all fecal samples. At the genus level, Bacteroides was the common dominant bacteria, while there were some differences in other dominant bacteria genera. There were significant differences in fecal microbial composition between the golden pheasants from Tianjin Zoo and Beijing Wildlife Park. The metabolic analysis and functional prediction suggested that the gut microbiota composition and host metabolism were influenced by dietary interventions and living conditions. The results of this study provide the basis for further research of intestinal microbial of L. nycthemera and C. pictus, and valuable insights for conservation of related species.

ObjectivesTo investigate the causal relationships between pneumoconiosis and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and gout.MethodsThe random-effects inverse variance weighted (IVW) approach was utilized to explore the causal effects of the instrumental variables (IVs). Sensitivity analyses using the MR-Egger and weighted median (WM) methods were did to investigate horizontal pleiotropy. A leave-one-out analysis was used to avoid the bias resulting from single-nucleotide polymorphisms (SNPs).ResultsThere was no causal association between pneumoconiosis and SLE, RA or gout in the European population [OR = 1.01, 95% CI: 0.94–1.10, p = 0.74; OR = 1.00, 95% CI: 0.999–1.000, p = 0.50; OR = 1.00, 95% CI: 1.000–1.001, p = 0.55]. Causal relationships were also not found in pneumoconiosis due to asbestos and other mineral fibers and SLE, RA and gout [OR = 1.01, 95% CI: 0.96–1.07, p = 0.66; OR = 1.00, 95% CI: 1.00–1.00, p = 0.68; OR = 1.00, 95% CI: 1.00–1.00, p = 0.20].ConclusionOur study suggests that pneumoconiosis may have no causal relationship with the three inflammatory immune diseases.

Vitreous replacement is a commonly employed method for treating a range of ocular diseases, including posterior vitreous detachment, complex retinal detachment, diabetic retinopathy, macular hole, and ocular trauma. Various clinical substitutes for vitreous include air, expandable gas, silicone oil, heavy silicone oil, and balanced salt solution. However, these substitutes have drawbacks such as short retention time, cytotoxicity, high intraocular pressure, and the formation of cataracts, rendering them unsuitable for long-term treatment. Polymeric hydrogels possess the potential to serve as ideal vitreous substitutes due to their structure-mimicking to natural vitreous and adjustable mechanical properties. Replacement with hydrogels as the tamponade can help maintain the shape of the eyeball, apply pressure to the detached retina, and ensure the metabolic transport of substances without impairing vision. This literature review examines the required properties of artificial vitreous, including the optical properties, rheological properties, expansive force action, and physiological and biochemical functions of chemically and physically crosslinked hydrogels. The strategies for enhancing the biocompatibility and injectability of hydrogels are also summarized and discussed. From a clinical ophthalmology perspective, this paper presents the latest developments in vitreous replacement, providing clinicians with a comprehensive understanding of hydrogel clinical applications, which offers guidance for future design directions and methodologies for hydrogel development.

Abstract Intrahepatic cholangiocarcinoma (ICC) accounts for 20% of liver malignancies with a 5-year survival rate of 35% at best with limited prognostic predictors. Lung Immune Prognostic Index (LIPI) is a novel prognostic factor in pulmonary cancers. In this study, we developed a modified prognostic model from LIPI called intrahepatic immune prognostic index (IIPI) for ICC. A retrospectively study was conducted at Liver Transplant Center of West China Hospital between January 2015 and January 2023. Hematological factors and clinical features of ICC patients were collected and analyzed. The area under curve (AUC) and optimal cuff-off of each single hematological factor was calculated. In this study, derived neurtrophil to lymphocyte ratio (dNLR), arbohydrate antigen199 (CA199) and carcinoembryonic antigen (CEA) have higher AUC values. LIPI was composed of dNLR and was further modified by combing CA199 and CEA, forming the IIPI. The IIPI consists of four grades which are None, Light, Moderate and Severe. Compared to other prognostic factors, IIPI exhibited better ability to predict overall survival. The multivariate analysis indicated that cirrhosis, differentiation, hilar invasion and IIPI were independent prognostic factors for ICC patients. An IIPI-based nomogram was also established and could predict the overall survival. In addition, the subgroup analyses based on clinical prognostic factors showed that the IIPI exhibited excellent prognostic influence. IIPI model is suitable for predicting the prognosis of postoperative ICC patients. Further research is needed to explore the relationship between postoperative recurrence and metastasis of ICC patients and IIPI.

Abstract The role of PRKAG2 in the maintenance of heart function is well established, but little is known about how PRKAG2 is regulated in cardiomyocytes. In this study, we investigated the role of the lncRNA PRKAG2-AS, which is present at the PRKAG2 promoter, in the regulation of PRKAG2 expression. PRKAG2-AS expression was predominantly nuclear, as determined by RNA nucleoplasmic separation and fluorescence in situ hybridization. Knockdown of PRKAG2-AS in the nucleus, but not the cytoplasm, significantly decreased the expression of PRKAG2b and PRKAG2d. Interestingly, we found that PRKAG2-AS and its target genes, PRKAG2b and PRKAG2d, were reduced in the hearts of patients with ischemic cardiomyopathy, suggesting a potential role for PRKAG2-AS in myocardial ischemia. Indeed, knockdown of PRKAG2-AS in the nucleus resulted in apoptosis of cardiomyocytes. We further elucidated the mechanism by which PRKAG2-AS regulates PRKAG2 transcription by identifying 58 PRKAG2-AS interacting proteins. Among them, PPARG was selected for further investigation based on its correlation and potential interaction with PRKAG2-AS in regulating transcription. Overexpression of PPARG, or its activation with rosiglitazone, led to a significant increase in the expression of PRKAG2b and PRKAG2d in cardiomyocytes, which could be attenuated by PRKAG2-AS knockdown. This finding suggests that PRKAG2-AS mediates, at least partially, the protective effects of rosiglitazone on hypoxia-induced apoptosis. However, given the risk of rosiglitazone in heart failure, we also examined the involvement of PRKAG2-AS in this condition and found that PRKAG2-AS, as well as PRKAG2b and PRKAG2d, was elevated in hearts with dilated cardiomyopathy (DCM) and that overexpression of PRKAG2-AS led to a significant increase in PRKAG2b and PRKAG2d expression, indicating that up-regulation of PRKAG2-AS may contribute to the mechanism of heart failure by promoting transcription of PRKAG2. Consequently, proper expression of PRKAG2-AS is essential for maintaining cardiomyocyte function, and aberrant PRKAG2-AS expression induced by hypoxia or other stimuli may cause cardiac dysfunction.

Abstract Background There is increasing evidence that recombinant human P2Y purinoceptor 6 (P2RY6) may be involved in inflammatory responses. However, the role of P2RY6 in lung adenocarcinoma (LUAD) remains unknown. Methods We used transcriptomic, genomic, single-cell transcriptomic, and methylation sequencing data from The Cancer Genome Atlas database to analyze the aberrant status and prognostic value of P2RY6 in a variety of tumors. The LUAD single-cell sequencing dataset was used to explore the effect of P2RY6 on the tumor microenvironment. Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) was used to quantify immune cells in the tumor microenvironment. We also analyzed the correlation of P2RY6 with immune checkpoints and immune regulation-related genes. The correlation of between tumor mutation burden (TMB), microsatellite instability (MSI), and P2RY6 expression was also analyzed simultaneously. Tissue microarray and immunohistochemistry were employed to assess the expression of P2RY6 in internal tumor samples. Results Our findings indicate that P2RY6 exhibits significantly higher expression levels in various cancer tissues, particularly in LUAD. High expression of P2RY6 was closely associated with a poor prognosis for patients, and it plays a role in regulating immune-related pathways, such as cytokine-cytokine receptor interaction. Notably, P2RY6 expression is closely linked to the abundance of CD8 + T cells. Furthermore, we have developed a P2RY6-related inflammation prediction model that demonstrates promising results in predicting the prognosis of LUAD patients, with an AUC (area under the curve) value of 0.83. This performance is significantly better than the traditional TNM staging system. Through single-cell transcriptome sequencing analysis, we observed that high P2RY6 expression is associated with increased intercellular communication. Additionally, pathway enrichment analysis revealed that P2RY6 influences antigen presentation and processing pathways within the LUAD microenvironment. Conclusions This study suggests that P2RY6 would be a new target for immunotherapy in LUAD.

Abstract Medical crowdsourcing competitions can help patients get more efficient and comprehensive treatment advice than “one-to-one” service, and doctors should be encouraged to actively participate. In the crowdsourcing competitions, winning the crowdsourcing competition is the driving force for doctors to continue to participate in the service. Therefore, how to improve the winning probability needs to be revealed. From the service content and competitive environment perspectives, this study introduces doctor competence indicators to investigate the key influence factors of doctors’ wins on the online platform. The results show that the emotional interaction in doctors’ service content positively influences doctors’ wins. However, the influence of information interaction presents heterogeneity. Conclusive information helps doctors win, while suggestive information negatively affects them. For the competitive environment, the competitive environment negatively moderates the relationship between doctors’ service content and doctors’ wins. The results of this study provide important contributions to the research on crowdsourcing competitions and online healthcare services and guide the participants of the competition, including patients, doctors, and platforms.

Abstract Background Prothrombin induced by vitamin K absence‐II (PIVKA‐II) and Alpha‐fetoprotein (AFP) have been widely used as diagnostic markers in hepatocellular carcinoma (HCC), but the prognostic values of the two serum markers and their clinical usefulness in patient selection for different surgical approaches remain largely unclear. Methods HCC patients received surgical treatment between 2015 and 2019 were included. Patients were divided into four statuses according to the serum PIVKA‐II and AFP secretion status: PIVKA‐II (−) AFP (−) (status 1); PIVKA‐II (+) AFP (−) (status 2); PIVKA‐II (−) AFP (+) (status 3); PIVKA‐II (+) AFP (+) (status 4). Kaplan–Meier analyses were conducted to compare the survivals of the four groups and the HCC patients received different surgical interventions; time‐dependent AUC curves were introduced to evaluate the prognostic value of the PIV‐AFP status; Cox regression model was used to identify prognostic indexes for overall survival (OS) and recurrence‐free survival (RFS). Results A total of 518 patients were included. Patients with PIVKA‐II (+) and APF (+) presented significantly decreased OS and RFS comparing to the other statuses. The areas under ROC curves of PIV‐AFP status in predicting OS and RFS were superior to the PIVKA‐II or the AFP alone. The HCC patients in early stages with PIVKA‐II (+) and APF (+) had worse RFS when received laparoscopic hepatectomy than those who received open hepatectomy, whereas there was no difference in other secretion statuses. The PIVKA‐II (+) and AFP (+) secretion status was an independent risk factor for OS, RFS. Conclusions The PIV‐AFP secretion status is of favorable clinical utility in predicting the OS and RFS of the HCC patients; extra caution is needed when applicated the laparoscopic approach in the HCC patients with PIVKA‐II (+) and AFP (+).

Abstract 3D ionic covalent organic framework (COF) membranes, which are envisioned to be able to break the trade-off between ion conductivity and ion selectivity, are waiting for exploitation. Herein, we report the fabrication of a 3D sulfonic acid-functionalized COF membrane (3D SCOF) for efficient and selective ion transport, using dual acid-mediated interfacial polymerization strategy. The 3D SCOF membranes possess highly interconnected ion transport channels, ultramicroporous pore sizes (0.97 nm), and abundant sulfonate groups (with a high ion exchange capacity of 4.1 mmol g−1), leading to high proton conductivity of 843 mS cm−1 at 90 °C. When utilized in osmotic energy conversion, a high power density of 21.2 W m−2, and a remarkable selectivity of 0.976 and thus an exceptional energy conversion efficiency of 45.3% are simultaneously achieved. This work provides an alternative approach to 3D ionic COF membranes and promotes the applications of 3D COFs in ion transport and separation.