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Background Cervical cancer, a prevalent malignancy in women, has a well-established etiology and can be effectively prevented through standardized screening. The WHO recommends HPV testing as the primary method for cervical cancer screening. Understanding the status of high-risk human papillomavirus (hrHPV) infection in Chengdu is crucial for optimizing primary hrHPV screening. Objective To investigate the hrHPV infection status among cervical cancer screening participants aged 35-64 years in Chengdu, and explore the related factors affecting the positive detection rate of hrHPV. Methods We retrospectively analyzed data from 459 433 women who received free cervical cancer screening in Chengdu in 2023, sourced from the "Chengdu Reproductive Health Database of Women of Childbearing Age". We analyzed the overall distribution of different hrHPV genotypes and the distribution of hrHPV subtypes in patients with cervical lesions, and compared the hrHPV infection in different populations. Multivariate Logistic regression models identified factors affecting the positive detection rate of hrHPV. Results The hrHPV prevalence among participants was 11.65% (53 509/459 433), with an increase observed with age (χ2=1 501.082, P

Mg alloys with advantages of biocompatibility and biodegradability are considered as a new type of medical material with great potential. Compared with casting and additive manufacturing, Semi-solid powder forming (SPF) is a promising new technique to prepare medical Mg alloys due to the characteristics of fine microstructures, a short process cycle and good comprehensive properties. In this study, the micromechanism of Mg–6Zn mixed powder materials under a semi-solid isothermal and deformation station was analyzed and discussed based on the results of SEM, EDS, XRD, synchrotron radiation X-ray computed tomography (SRXCT) and kinetic analysis. The results show all the Zn powders melt and Mg powder dissolves into the liquid Zn to form a Zn–Mg liquid wrapping around the Mg powders the semi-solid isothermal state. The powder particle boundary blurred and transgranular liquation cracking (TLC) occurs under the loading force, making the powders being broken into fragments which spheroidize and coarsen afterward. Simultaneously, the dynamic model of Mg–6Zn mixed powders was deduced and established, which agrees well with the experimental results and can predict the actual liquid fraction during SPF. The pores reconstructed by SRXCT has a low connectivity, near-spherical morphology and flat surface, combined with encapsulated microstructure with finer grains and fewer secondary phases, which are beneficial to slow down the degradation rate. Finally, the micromechanism of SPF was concluded as atomic diffusion, liquid flowing and filling, transgranular liquation cracking (TLC) of particles as well as coarsening and spheroidizing of its fragments, which provides theoretical guidance for optimizing the forming process.

Abstract The tripartite motif (TRIM) protein family has been shown to play important roles in the occurrence and development of various tumors. However, the biological functions of TRIM47 and its regulatory mechanism in hepatocellular carcinoma (HCC) remain unexplored. Here, we showed that TRIM47 was upregulated in HCC tissues compared with adjacent normal tissues, especially at advanced stages, and associated with poor prognosis in HCC patients. Functional studies demonstrated that TRIM47 enhanced the migration and invasion ability of HCC cells in vitro and in vivo. Mechanistically, TRIM47 promotes HCC metastasis through interacting with SNAI1 and inhibiting its degradation by proteasome. Moreover, TRIM47 was di-methylated by CARM1 at its arginine 210 (R210) and arginine 582 (R582), which protected TRIM47 from the ubiquitination and degradation mediated by E3 ubiquitin ligase complex CRL4CRBN. Collectively, our study reveals a pro-metastasis role of TRIM47 in HCC, unveils a unique mechanism controlling TRIM47 stability by CARM1 mediated arginine methylation, and highlights the role of the CARM1-CRL4CRBN-TRIM47-SNAI1 axis in HCC metastasis. This work may provide potential therapeutic targets for metastatic HCC treatment.

In order to explore the differences of taste and metabolites of different Ganoderma lucidum strains, the fruiting bodies of different Ganoderma lucidum strains were taken as samples, the taste of aqueous extracts of 21 different Ganoderma lucidum strains were determined by electronic tongue. The non-targeted metabonomics techniques of ultra high performance liquid chromatography and mass spectrometry were used. Combined with principal component analysis (PCA) and orthogonal partial least square discriminant analysis (OPLS-DA) and other statistical methods based on the results of taste cluster analysis, three different Ganoderma lucidum strains (GL229, GL219, GL236) were selected for metabolite identification and analysis. The results showed that the response values of sour, umami, bitter and salty taste of water extracts of different Ganoderma lucidum strains were quite different. A total of 6057 metabolites were identified from the water extracts of three different Ganoderma lucidum strains. There were 1282, 1311 and 1966 differential metabolites between GL219 and GL229, GL236 and GL229, GL219 and GL236, respectively. There were 123 differential metabolites among the three control groups, including organic acids and their derivatives, benzene ring compounds, organic oxygen compounds, organic heterocyclic compounds, lipids and lipid compounds. The main differential metabolites were Jamaicamide C, 2-isopropylmalicacid, 1-naphthylamine, tyramine, genipin and so on. The differential metabolites L-glutamine, glutamine, cinchonine, solanidine, phenylacetaldehyde and dehydrocholicacid were flavor substances, which contributed to the taste differences of water extracts of different Ganoderma lucidum strains. This study showed that metabonomics could be used to analyze the compositions differences of Ganoderma lucidum with different taste. Therefore, it could provide a theoretical basis for the material basis of Ganoderma lucidum taste.

Objectives: Citrate, oxalate and cystine in 24-h urine are considered to be associated with the incidence and recurrence risk of urinary stone disease (USD). An evaluation of the LC-MS/MS kit for simultaneous quantification of the three analytes was undertaken. Design: & Methods: The analytical performance of the kit was investigated based on FDA, EMA and CLSI guidelines. To promote the standardization of sample storage, this kit has been applied to perform systematic pre-analytical stability study of these analytes in urine. Results: This method was validated with good linearity with accuracy of 93.1%–104 %. Intra-day and inter-day imprecision were ≤5.55 % and 5.34 %, respectively. Recoveries of citrate, oxalate and cystine added to clinical samples were in the range of 92.0–103 %, 94.8–100 % and 99.0–107 % with CV ≤ 5.52 %. It was recommended that urine preserved with hydrochloric acid could be preferable in consideration of both reliable test results and neglected sample heterogeneity. Conclusions: This kit is suitable for measurement of citrate, oxalate and cystine for understanding the etiology of urinary stones, and the proper storage of urine samples is crucial for the correctness of the test results.

Abstract Endoplasmic reticulum stress (ERS) is a cellular stress response characterized by excessive contraction of the endoplasmic reticulum (ER). It is a pathological hallmark of many diseases, such as diabetes, obesity, and neurodegenerative diseases. In the unique growth characteristic and varied microenvironment of cancer, high levels of stress are necessary to maintain the rapid proliferation and metastasis of tumor cells. This process is closely related to ERS, which enhances the ability of tumor cells to adapt to unfavorable environments and promotes the malignant progression of cancer. In this paper, we review the roles and mechanisms of ERS in tumor cell proliferation, apoptosis, metastasis, angiogenesis, drug resistance, cellular metabolism, and immune response. We found that ERS can modulate tumor progression via the unfolded protein response (UPR) signaling of IRE1, PERK, and ATF6. Targeting the ERS may be a new strategy to attenuate the protective effects of ERS on cancer. This manuscript explores the potential of ERS-targeted therapies, detailing the mechanisms through which ERS influences cancer progression and highlighting experimental and clinical evidence supporting these strategies. Through this review, we aim to deepen our understanding of the role of ER stress in cancer development and provide new insights for cancer therapy.

Abstract Background Colorectal cancer (CRC) is the second most common malignant tumor worldwide, and its incidence rate increases annually. Early diagnosis and treatment are crucial for improving the prognosis of patients with colorectal cancer. Circular RNAs are noncoding RNAs with a closed-loop structure that play a significant role in tumor development. However, the role of circular RNAs in CRC is poorly understood. Methods The circular RNA hsa_circ_0000467 was screened in CRC circRNA microarrays using a bioinformatics analysis, and the expression of hsa_circ_0000467 in CRC tissues was determined by in situ hybridization. The associations between the expression level of hsa_circ_0000467 and the clinical characteristics of CRC patients were evaluated. Then, the role of hsa_circ_0000467 in CRC growth and metastasis was assessed by CCK8 assay, EdU assay, plate colony formation assay, wound healing assay, and Transwell assay in vitro and in a mouse model of CRC in vivo. Proteomic analysis and western blotting were performed to investigate the effect of hsa_circ_0000467 on c-Myc signaling. Polysome profiling, RT‒qPCR and dual-luciferase reporter assays were performed to determine the effect of hsa_circ_0000467 on c-Myc translation. RNA pull-down, RNA immunoprecipitation (RIP) and immunofluorescence staining were performed to assess the effect of hsa_circ_0000467 on eIF4A3 distribution. Results In this study, we found that the circular RNA hsa_circ_0000467 is highly expressed in colorectal cancer and is significantly correlated with poor prognosis in CRC patients. In vitro and in vivo experiments revealed that hsa_circ_0000467 promotes the growth and metastasis of colorectal cancer cells. Mechanistically, hsa_circ_0000467 binds eIF4A3 to suppress its nuclear translocation. In addition, it can also act as a scaffold molecule that binds eIF4A3 and c-Myc mRNA to form complexes in the cytoplasm, thereby promoting the translation of c-Myc. In turn, c-Myc upregulates its downstream targets, including the cell cycle-related factors cyclin D2 and CDK4 and the tight junction-related factor ZEB1, and downregulates E-cadherin, which ultimately promotes the growth and metastasis of CRC. Conclusions Our findings revealed that hsa_circRNA_0000467 plays a role in the progression of CRC by promoting eIF4A3-mediated c-Myc translation. This study provides a theoretical basis and molecular target for the diagnosis and treatment of CRC.

Abstract Hepatocellular carcinoma (HCC) represents a major global health threat with diverse and complex pathogenesis. Aldo–keto reductase family 1 member B10 (AKR1B10), a tumor-associated enzyme, exhibits abnormal expression in various cancers. However, a comprehensive understanding of AKR1B10's role in HCC is lacking. This study aims to explore the expression characteristics of AKR1B10 in HCC and its correlation with clinicopathological features, survival prognosis, and tumor immune microenvironment, further investigating its role and potential regulatory mechanisms in HCC. This study conducted comprehensive analyses using various bioinformatics tools and databases. Initially, differentially expressed genes related to HCC were identified from the GEO database, and the expression of AKR1B10 in HCC and other cancers was compared using TIMER and GEPIA databases, with validation of its specificity in HCC tissue samples using the HPA database. Furthermore, the relationship of AKR1B10 expression with clinicopathological features (age, gender, tumor size, staging, etc.) of HCC patients was analyzed using the TCGA database's LIHC dataset. The impact of AKR1B10 expression levels on patient prognosis was evaluated using Kaplan–Meier survival analysis and the Cox proportional hazards model. Additionally, the correlation of AKR1B10 expression with tumor biology-related signaling pathways and tumor immune microenvironment was studied using databases like GSEA, Targetscan, and others, identifying microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) that regulate AKR1B10 expression to explore potential regulatory mechanisms. Elevated AKR1B10 expression was significantly associated with gender, primary tumor size, and fibrosis stage in HCC tissues. High AKR1B10 expression indicated poor prognosis and served as an independent predictor for patient outcomes. Detailed mechanism analysis revealed a positive correlation between high AKR1B10 expression, immune cell infiltration, and pro-inflammatory cytokines, suggesting a potential DANCR-miR-216a-5p-AKR1B10 axis regulating the tumor microenvironment and impacting HCC development and prognosis. The heightened expression of AKR1B10 in HCC is not only related to significant clinical-pathological traits but may also influence HCC progression and prognosis by activating key signaling pathways and altering the tumor immune microenvironment. These findings provide new insights into the role of AKR1B10 in HCC pathogenesis and highlight its potential as a biomarker and therapeutic target.

BackgroundThe prognostic value and immune significance of T-cell proliferation regulators (TCRs) in hepatocellular carcinoma (HCC) have not been previously reported. This study aimed to develop a new prognostic model based on TCRs in patients with HCC.MethodThis study used The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) and International Cancer Genome Consortium-Liver Cancer-Riken, Japan (ICGC-LIRI-JP) datasets along with TCRs. Differentially expressed TCRs (DE-TCRs) were identified by intersecting TCRs and differentially expressed genes between HCC and non-cancerous samples. Prognostic genes were determined using Cox regression analysis and were used to construct a risk model for HCC. Kaplan-Meier survival analysis was performed to assess the difference in survival between high-risk and low-risk groups. Receiver operating characteristic curve was used to assess the validity of risk model, as well as for testing in the ICGC-LIRI-JP dataset. Additionally, independent prognostic factors were identified using multivariate Cox regression analysis and proportional hazards assumption, and they were used to construct a nomogram model. TCGA-LIHC dataset was subjected to tumor microenvironment analysis, drug sensitivity analysis, gene set variation analysis, and immune correlation analysis. The prognostic genes were analyzed using consensus clustering analysis, mutation analysis, copy number variation analysis, gene set enrichment analysis, and molecular prediction analysis.ResultsAmong the 18 DE-TCRs, six genes (DCLRE1B, RAN, HOMER1, ADA, CDK1, and IL1RN) could predict the prognosis of HCC. A risk model that can accurately predict HCC prognosis was established based on these genes. An efficient nomogram model was also developed using clinical traits and risk scores. Immune-related analyses revealed that 39 immune checkpoints exhibited differential expression between the high-risk and low-risk groups. The rate of immunotherapy response was low in patients belonging to the high-risk group. Patients with HCC were further divided into cluster 1 and cluster 2 based on prognostic genes. Mutation analysis revealed that HOMER1 and CDK1 harbored missense mutations. DCLRE1B exhibited an increased copy number, whereas RAN exhibited a decreased copy number. The prognostic genes were significantly enriched in tryptophan metabolism pathways.ConclusionsThis bioinformatics analysis identified six TCR genes associated with HCC prognosis that can serve as diagnostic markers and therapeutic targets for HCC.

Abstract Background The aim of the study was to investigate whether the expression of CD27−CD38+ in interferon (IFN)-γ+CD4+ T cells stimulated by the specific antigen early secreted antigenic target-6 (ESAT-6)/culture filter protein-10 (CFP-10) could be a potential new therapeutic evaluation indicator for anti-tuberculosis (TB) treatment. Methods Newly diagnosed active pulmonary TB patients, latent TB infection (LTBI) and healthy controls were enrolled from January 2021 to December 2021. PTB patients were treated by standard anti-TB regimen 2HREZ/4HR (2 months of isoniazid (H), rifampin (R), ethambutol (E), and pyrazinamide (Z) followed by 4 months of isoniazid (H) and rifampin (R)). The difference of CD27−CD38+ expression in IFN-γ+CD4+ T cells before treatment, 2 months after treatment, and 6 months after treatment were compared. Results Total 45 PTB patients, 38 LTBI cases and 43 healthy controls were enrolled. The expression of CD27−CD38+ decreased significantly after anti-TB treatment and was comparable with that in LTBI and healthy controls when the 6-month anti-TB treatment course was completed. The decline rate of CD27−CD38+ between 6 months after treatment and baseline was positively correlated with erythrocyte sedimentation rate (r = 0.766, P

Abstract Cellular metabolism is the fundamental process by which cells maintain growth and self‐renewal. It produces energy, furnishes raw materials, and intermediates for biomolecule synthesis, and modulates enzyme activity to sustain normal cellular functions. Cellular metabolism is the foundation of cellular life processes and plays a regulatory role in various biological functions, including programmed cell death. Ferroptosis is a recently discovered form of iron‐dependent programmed cell death. The inhibition of ferroptosis plays a crucial role in tumorigenesis and tumor progression. However, the role of cellular metabolism, particularly glucose and amino acid metabolism, in cancer ferroptosis is not well understood. Here, we reviewed glucose, lipid, amino acid, iron and selenium metabolism involvement in cancer cell ferroptosis to elucidate the impact of different metabolic pathways on this process. Additionally, we provided a detailed overview of agents used to induce cancer ferroptosis. We explained that the metabolism of tumor cells plays a crucial role in maintaining intracellular redox homeostasis and that disrupting the normal metabolic processes in these cells renders them more susceptible to iron‐induced cell death, resulting in enhanced tumor cell killing. The combination of ferroptosis inducers and cellular metabolism inhibitors may be a novel approach to future cancer therapy and an important strategy to advance the development of treatments.

Inhibiting the death receptor 3 (DR3) signaling pathway in group 3 innate lymphoid cells (ILC3s) presents a promising approach for promoting mucosal repair in individuals with ulcerative colitis (UC). Paeoniflorin, a prominent component of Paeonia lactiflora Pall., has demonstrated the ability to restore barrier function in UC mice, but the precise mechanism remains unclear. In this study, we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s. C57BL/6 mice were subjected to random allocation into 7 distinct groups, namely the control group, the 2 % dextran sodium sulfate (DSS) group, the paeoniflorin groups (25, 50, and 100 mg/kg), the anti-tumor necrosis factor-like ligand 1A (anti-TL1A) antibody group, and the IgG group. We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry, respectively. Meanwhile, DR3-overexpressing MNK-3 cells and 2 % DSS-induced Rag1−/− mice were used for verification. The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier. Simultaneously, paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines (Interleukin-17A, Granulocyte-macrophage colony stimulating factor, and Interleukin-22). Alternatively, paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage independently of the adaptive immune system. We additionally confirmed that paeoniflorin-conditioned medium (CM) restored the expression of tight junctions in Caco-2 cells via coculture. In conclusion, paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner, and its mechanism is associated with the inhibition of the DR3 signaling pathway.

Abstract BackgroundThe use of chronic disease information systems in hospitals and communities plays a significant role in disease prevention, control, and monitoring. However, there are several limitations to these systems, including that the platforms are generally isolated, the patient health information and medical resources are not effectively integrated, and the “Internet Plus Healthcare” technology model is not implemented throughout the patient consultation process. ObjectiveThe aim of this study was to evaluate the efficiency of the application of a hospital case management information system in a general hospital in the context of chronic respiratory diseases as a model case. MethodsA chronic disease management information system was developed for use in general hospitals based on internet technology, a chronic disease case management model, and an overall quality management model. Using this system, the case managers provided sophisticated inpatient, outpatient, and home medical services for patients with chronic respiratory diseases. Chronic respiratory disease case management quality indicators (number of managed cases, number of patients accepting routine follow-up services, follow-up visit rate, pulmonary function test rate, admission rate for acute exacerbations, chronic respiratory diseases knowledge awareness rate, and patient satisfaction) were evaluated before (2019‐2020) and after (2021‐2022) implementation of the chronic disease management information system. ResultsBefore implementation of the chronic disease management information system, 1808 cases were managed in the general hospital, and an average of 603 (SD 137) people were provided with routine follow-up services. After use of the information system, 5868 cases were managed and 2056 (SD 211) patients were routinely followed-up, representing a significant increase of 3.2 and 3.4 times the respective values before use (UPP(P ConclusionsUse of a chronic disease management information system improves the quality of chronic respiratory disease case management and reduces the admission rate of patients owing to acute exacerbations of their diseases.

BackgroundTraditional microbiological detection methods used to detect pulmonary infections in people living with HIV (PLHIV) are usually time-consuming and have low sensitivity, leading to delayed treatment. We aimed to evaluate the diagnostic value of metagenomics next-generation sequencing (mNGS) for microbial diagnosis of suspected pulmonary infections in PLHIV.MethodsWe retrospectively analyzed PLHIV who were hospitalized due to suspected pulmonary infections at the sixth people hospital of Zhengzhou from November 1, 2021 to June 30, 2022. Bronchoalveolar lavage fluid (BALF) samples of PLHIV were collected and subjected to routine microbiological examination and mNGS detection. The diagnostic performance of the two methods was compared to evaluate the diagnostic value of mNGS for unknown pathogens.ResultsThis study included a total of 36 PLHIV with suspected pulmonary infections, of which 31 were male. The reporting period of mNGS is significantly shorter than that of CMTs. The mNGS positive rate of BALF samples in PLHIV was 83.33%, which was significantly higher than that of smear and culture (44.4%, P

Background: This is a retrospective study aimed at comparing the clinical efficacy and safety between drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE) and conventional TACE (C-TACE) in the treatment of unresectable hepatocellular carcinoma. Methods: From July 2019 to April 2021, we enrolled 282 patients with unresectable hepatocellular carcinoma who were admitted to our hospital, of which 179 and 103 were in the DEB-TACE and C-TACE groups, respectively. General information was collected, and treatment effects were evaluated following the modified Response Evaluation Criteria in Solid Tumors. To compare the indexes of liver and kidney function, routine blood and coagulation were collected before treatment, and 1 day, 1 month, 3 months, and 6 months postoperatively. Postoperative adverse reactions (ie, fever, nausea, vomiting, anorexia, abdominal pain) were recorded to evaluate the safety of treatment. The two groups’ progression-free survival and overall survival were also calculated to assess the treatment effect. Results: Preoperatively, the bilirubin, transaminase, and absolute neutrophil values between the two groups were not statistically significant ( P > .05). At 1 month postoperatively, the absolute neutrophil values were significantly higher in the DEB-TACE group than those in the C-TACE group ( P

BackgroundInfant botulism is caused by botulinum neurotoxin (BoNT), which is mainly produced by Clostridium botulinum. However, there is a lack of longitudinal cohort studies on infant botulism. Herein, we have constructed a cross-sectional and longitudinal cohort of infants infected with C. botulinum. Our goal was to reveal the differences in the intestinal microbiota of botulism-infected and healthy infants as well as the dynamic changes over time through multi-omics analysis.MethodsWe performed 16S rRNA sequencing of 20 infants’ stools over a period of 3 months and conducted whole genome sequencing of isolated C. botulinum strains from these laboratory-confirmed cases of infant botulism. Through bioinformatics analysis, we focused on the changes in the infants’ intestinal microbiota as well as function over time series.ResultsWe found that Enterococcus was significantly enriched in the infected group and declined over time, whereas Bifidobacterium was significantly enriched in the healthy group and gradually increased over time. 18/20 isolates carried the type B 2 botulinum toxin gene with identical sequences. In silico Multilocus sequence typing found that 20\u00B0C. botulinum isolates from the patients were typed into ST31 and ST32.ConclusionDifferences in intestinal microbiota and functions in infants were found with botulism through cross-sectional and longitudinal studies and Bifidobacterium may play a role in the recovery of infected infants.

Anaplasma capra is an emerging tickborne zoonotic pathogen in the genus Anaplasma, family Anaplasmataceae, and was initially identified in blood samples from asymptomatic goats (Capra aegagrus hircus) and a febrile [...]

Abstract Several studies have reported the effects of DJ-1 gene and miR-199a/b-3p on HCC development. However, whether miR-199a/b-3p regulates HCC progression through a novel compensatory signaling pathway involving DJ-1, Ras, and PI3K/AKT remains unknown. We used (TCGA, HPA, miRWalk and Target scan) databases, cancer and para-tissue HCC patients, dual-luciferase reporter gene analysis, proteomic imprinting, qPCR, cell proliferation, scratch, transport, and flow cytometry to detect the molecular mechanism of DJ-1 and miR-199a/b-3p co-expression in HCC cell lines. Bioinformatics analysis showed that DJ-1 was highly expressed in HCC ((P

AIM: To analyze the current status, hotspots and trends of studies on the treatments of diabetic retinopathy.METHODS: Relevant literatures on diabetic retinopathy in Chinese National Knowledge Infrastructure(CNKI)and Web of Science core collection database were retrieved from creation to June 15, 2023, and CiteSpace 6.2.R2 and VOSviewer were used to conduct visualized analysis with the country/issuing institution, research author and keywords.RESULTS: A total of 5 919 Chinese literatures and 11 475 English literatures were included. The top three countries with global publications are the United States, China and the United Kingdom, respectively. The top three institutions for issuing articles at abroad are Harvard Medical School, Harvard University and Johns Hopkins University, while the top three institutions for issuing articles in China are the Eye Hospital of China Academy of Chinese Medical Science, Hunan University of Chinese Medicine, and Zhongshan Ophthalmic Center of Sun Yat-sen University. The research results of high-frequency keywords in both Chinese and English show that the laser photocoagulation, vitrectomy, traditional Chinese medicine therapy, vascular endothelial growth factor and ranibizumab are research hotspots.CONCLUSIONS: In recent years, the research hotspots of diabetic retinopathy mainly focus on surgery, vascular protective agents, traditional Chinese medicine therapy, anti-vascular endothelial growth factor, etc., and the research trend mainly focuses on anti-vascular endothelial growth factor drugs.

Infectious spleen and kidney necrosis virus (ISKNV) has brought huge economic loss to the aquaculture industry. Through interfering with the viral replication and proliferation process that depends on host cells, its pathogenicity can be effectively reduced. In this study, we investigated the role of asparagine metabolites in ISKNV proliferation. The results showed that ISKNV infection up-regulated the expression of some key enzymes of the asparagine metabolic pathway in Chinese perch brain (CPB) cells. These key enzymes, including glutamic oxaloacetic transaminase 1/2 (GOT1/2) and malate dehydrogenase1/2 (MDH1/2) associated with the malate-aspartate shuttle (MAS) pathway and asparagine synthetase (ASNS) involved in the asparagine biosynthesis pathway, were up-regulated during ISKNV replication and release stages. In addition, results showed that the production of ISKNV was significantly reduced by inhibiting the MAS pathway or reducing the expression of ASNS by 1.3-fold and 0.6-fold, respectively, indicating that asparagine was a critical limiting metabolite for ISKNV protein synthesis. Furthermore, when asparagine was added to the medium without glutamine, ISKNV copy number was restored to 92% of that in the complete medium, indicating that ISKNV could be fully rescued from the absence of glutamine by supplementing asparagine. The above results indicated that asparagine was a critical factor in limiting the effective replication of ISKNV, which provided a new idea for the treatment of aquatic viral diseases.

AIM: To explore the hotspots and frontiers of genetic research on pediatric cataracts. METHODS: Global publications from 2013 to 2022 related to genes in pediatric cataracts were extracted from the Web of Science Core Collection, and were analyzed in terms of the publication counts, countries, journals, authors, keywords, cited references, subject categories, and the underlying hotspots and frontiers. RESULTS: Totally 699 publications were included in the final analysis. The predominant actors were identified, with China (n=240) and PLoS One (n=33) being the most productive country and journal respectively. The research hotspots extracted from keywords were crystallin gene mutations, pathogenicity evaluation, phenotypes of ocular and neurodevelopmental abnormalities, genes encoding membrane proteins, and diagnosis of multisystemic disorders. The co-cited articles formed 10 clusters of research topics, including FYCO1 (56 items), mutation screening (43 items), gap junction (29 items), the Warburg Micro syndrome (29 items), ephrin-A5 (28 items), novel mutation (24 items), eye development and function (22 items), cholestanol (7 items), OCRL (6 items), and pathogenicity prediction (3 items). The research frontiers were FYCO1, ephrin-A5, and cholestanol. Cell biology showed the strongest bridging effects among different disciplines in the field (betweenness centrality=0.44). CONCLUSION: With the progress in next-generation sequencing and multidisciplinary collaboration, genetic research on pediatric cataracts broadens the knowledge scope of the crystalline lens, as well as other organs and systems, shedding light on the molecular mechanisms of systemic diseases. Cell biology may integrate multidisciplinary content to address cutting-edge issues in the field.

Abstract Background Preeclampsia complicated with hypofibrinogenemia is a rare disorder. We report two cases of severe preeclampsia complicated with hypofibrinogenemia followed by postpartum haemorrhage (PPH). Case Two women diagnosed as preeclampsia and hypofibrinogenemia developed severe PPH after undergoing Cesarean sections. Besides supplement with fibrinogen concentrate and supportive treatment, the second patient got administration of heparin after delivery and bleeding was stopped. The haemorrhage in case 1 didn’t disappear until an hysterectomy. The two patients both recovered and were discharged soon. Conclusions Severe preeclampsia patients with hypofibrinogenemia could suffer PPH. It’s necessary to detect and master coagulation function. Heparin could be considered to balance hypercoagulation and hypocoagulation to avoid catastrophic haemorrhage and hysterectomy.

Abstract Soil bacterial communities regulate nutrient cycling and plant growth in forests. Although these bacterial communities vary with soil nutrients and plant traits, the variation and degree with soil horizons in different forest types remain unclear. Here, bacterial communities of 44 soil samples from organic horizon (O horizon) and mineral horizon (M horizon) of three forest types (Cunninghamia, broad-leaved and Pinus forests) in subtropical forests of Dabie Mountain, China were analyzed based on amplicon sequencing. We assessed the effects of soil horizons and forest types on bacterial communities. The results showed that the bacterial richness and diversity were significantly higher in the O horizon than in the M horizon. Furthermore, the bacterial community composition and functions were also remarkably different between the two soil horizons. Furthermore, forest types could affect bacterial community composition but not for diversity and functions. Moreover, soil organic matter, including the total organic carbon, available phosphorus, total organic nitrogen, available potassium, ammonium nitrogen, and pH were main drivers for bacterial community composition. The results propose robust evidence that soil horizons strongly driven bacterial community composition and diversity, and suggest that microhabitat of soil bacterial communities is important to maintain the stability of forest ecosystem.

Ratoon rice, the production of second crop from the dormant buds on the stubble after harvesting of the main crop, is considered an economic, environment-sound, and resource-efficient cropping system. This paper summarized the research progress of ratoon rice in Chongqing Municipality, the upper reaches of the Yangtze River, China in the past 30 years, and analyzed the physiological mechanisms behind the rice varieties with strong ratooning ability and the key practices for achieving high yield of ratoon rice. Ratooning ability and grain yield of the ratoon crop are highly and positively correlated with the initiation and growth of axillary buds, which can be promoted by optimizing variety selection, nutrient and water management, crop establishment method, stubble height, and harvesting method of the main crop. With implementation of those key practices, the grain yield could reach as high as 7.2 ​t ​ha−1 of the ratoon crop with the main crop harvested manually. Due to the shortage of rural labor, mechanical harvesting of the main crop becomes an inevitable option for the sustainable development of ratoon rice. In the future studies, there is need to develop specialized harvesting machines and crop management strategies for reducing the rolling damage to stubbles during mechanical harvesting of the main crop, and consequently achieving high and stable yield of mechanized ratoon rice.

Background: The sustainability and generalizability of China’s dynamic zero-COVID strategy on eliminating SARS-CoV-2 transmission has casted doubt globally, mainly because it has exacted high social and economic cost. This study aimed to estimate the disease burden during the first wave of Omicron in China and compared the cost-effectiveness of implementing a Real-world strategy (adjusted dynamic zero-COVID strategy) with two simulated strategies (routine and stricter dynamic zero-COVID strategy) to inform appropriate strategies for COVID-19 pandemic control. Methods: A dynamic state-transition simulation model was developed to compare the health and cost outcomes between different dynamic zero-COVID strategies. Omicron-related healthcare costs were estimated from the societal perspective. Epidemiological parameter values were derived from data of real-world or generated by model calibration; costs and effectiveness parameter values were informed either by local data or published literature. The primary outcomes were total social cost, disability adjusted life-years (DALYs) and net monetary benefit (NMB). Deterministic sensitivity analyses (DSA) and scenario analyses were performed to assess the model robustness. Results: The first wave of Omicron in Shanghai resulted in 47,646 DALYs lost and 415 billion RMB losses. At a willingness-to-pay threshold of 173,630 RMB (the GDP per capita of Shanghai in 2021) per DALY saved, the Real-world strategy was considered as the most cost-effective strategy due to its highest NMB (−407 billion). Results from DSA confirmed the robustness of our findings. Conclusion: Our finding supported the Real-world strategy taken by the Shanghai Municipal Government between March 1 and May 21, 2022 to control the first wave of Omicron outbreak. Moreover, our results indicated that whether the Stricter dynamic zero-COVID strategy is worth implementing at the beginning of the COVID-19 outbreak mainly depended on the infection rate of COVID-19 among primary contacts. Our analysis provides important evidence to inform policy makers to make appropriate decisions regarding COVID-19 pandemic management.

Abstract Background Implicit rationing of nursing care can adversely affect patient safety and the quality of care, and increase nurses’ burnout and turnover tendency. Implicit rationing care occurs at the nurse-to-patient level (micro-level), and nurses are direct participants. Therefore, the strategies based on experience of nurses to reduce implicit rationing care have more reference value and promotion significance. The aim of the study is to explore the experience of nurses to reduce implicit rationing care, thereby to provide references for conducting randomized controlled trials to reduce implicit rationing care. Methods This is a descriptive phenomenological study. Purpose sampling was conducted nationwide. There are 17 nurses were selected and semi-structured in-depth interviews were conducted. The interviews were recorded, transcribed verbatim and analyzed via thematic analysis. Results Our study found that nurses’ reported experience of coping with implicit rationing of nursing care contained three aspects: personal, resource, and managerial. Three themes were extracted from the results of the study: (1) improving personal literacy; (2) supplying and optimizing resources and (3) standardizing management mode. The improvement of nurses’ own qualities are the prerequisites, the supply and optimization of resources is an effective strategy, and clear scope of work has attracted the attention of nurses. Conclusion The experience of dealing with implicit nursing rationing includes many aspects. Nursing managers should be grounded in nurses’ perspectives when developing strategies to reduce implicit rationing of nursing care. Promoting the improvement of nurses’ skills, improving staffing level and optimizing scheduling mode are promising measures to reduce hidden nursing rationing.

Abstract Background The insect hemolymph (blood-equivalent fluid), composed of a large number of hemocytes (blood cells) and a variety of soluble immune effectors, is hostile for pathogens including fungi. In order to survive in the insect hemocoel (body cavity), the entomopathogenic fungus (EPF) has evolved two classical coping strategies, namely evasion and suppression of the host immune reactions. However, it remains unclear whether EPF has other ways of coping with host immunity. Results In this study, we demonstrated that Metarhizium rileyi (an EPF) infection by injection of blastospores into the hemocoel enhanced the plasma antibacterial activity of cotton bollworm (Helicoverpa armigera), which was partially due to the enhanced expression of antimicrobial peptides (AMPs). The early stage of M. rileyi infection induced the translocation of gut bacteria into the hemocoel, where they were subsequently cleared due to the enhanced plasma antibacterial activity. Further, we showed that the enhanced plasma antibacterial activity and AMP expression were attributable to M. rileyi but not the invasive gut bacteria (opportunistic bacteria). Elevated ecdysone (major steroid hormone in insects) levels in the hemolymph at 48 h post-M. rileyi infection might contribute to the enhanced expression of AMPs. The fungus-elicited AMPs, such as cecropin 3 or lebocin, exhibited potent inhibitory activity against the opportunistic bacteria but not against hyphal bodies. In addition, the opportunistic bacteria competed with hyphal bodies for amino acid nutrients. Conclusions M. rileyi infection induced the translocation of gut bacteria, and then the fungi activated and exploited its host humoral antibacterial immunity to eliminate opportunistic bacteria, preventing them from competing for nutrients in the hemolymph. Unlike the classical strategies, EPF utilizes to evade or suppress host immunity, our findings reveal a novel strategy of interaction between EPF and host immunity. Video Abstract

Abstract Stroke usually causes prolonged or lifelong disability, owing to the permanent loss of infarcted tissue. Although a variety of stem cell transplantation has been explored to improve neuronal defect behavior by enhancing neuroplasticity, it remains unknown whether the infarcted tissue can be reconstructed. We here cultured human cerebral organoids derived from human pluripotent stem cells (hPSCs) and transplanted them into the junction of the infarct core and the peri-infarct zone of NOD-SCID mice subjected to stroke. Months later, we found that the grafted organoids survived well in the infarcted core, differentiated into target neurons, repaired infarcted tissue, sent axons to distant brain targets, and integrated into the host neural circuit and thereby eliminated sensorimotor defect behaviors of stroke mice, whereas transplantation of dissociated single cells from organoids failed to repair the infarcted tissue. Our study offers a new strategy for reconstructing infarcted tissue via organoids transplantation thereby reversing stroke-induced disability.

This work used headspace solid-phase microextraction with gas chromatography–mass spectrometry (HS-SPME-GC–MS) to analyze the volatile components of hydrosols of Citrus × aurantium ‘Daidai’ and Citrus × aurantium L. dried buds (CAVAs and CADBs) by immersion and ultrasound–microwave synergistic-assisted steam distillation. The results show that a total of 106 volatiles were detected in hydrosols, mainly alcohols, alkenes, and esters, and the high content components of hydrosols were linalool, α-terpineol, and trans-geraniol. In terms of variety, the total and unique components of CAVA hydrosols were much higher than those of CADB hydrosols; the relative contents of 13 components of CAVA hydrosols were greater than those of CADB hydrosols, with geranyl acetate up to 15-fold; all hydrosols had a citrus, floral, and woody aroma. From the pretreatment, more volatile components were retained in the immersion; the relative contents of linalool and α-terpineol were increased by the ultrasound–microwave procedure; and the ultrasound–microwave procedure was favorable for the stimulation of the aroma of CAVA hydrosols, but it diminished the aroma of the CADB hydrosols. This study provides theoretical support for in-depth exploration based on the medicine food homology properties of CAVA and for improving the utilization rate of waste resources.

It is well known that the existing horizontal-well-drilling and hydraulic fracturing technology used to achieve large-scale, cost-effective production from immature to low–moderate-maturity continental shale in China, where the organic matter mainly exists in solid form, is fairly ineffective. To overcome the obstacles, in situ conversion technology seems feasible, while implementing it in the target layer along with estimating the amount of expected recoverable hydrocarbon in such shale formations seems difficult. This is because there are no guidelines for choosing the most appropriate method and selecting relevant key parameters for this purpose. Hence, based on thermal simulation experiments during the in situ conversion of crude oil from the Triassic Chang 73 Formation in the Ordos Basin and the Cretaceous Nenjiang Formation in the Songliao Basin, this deficiency in knowledge was addressed. First, relationships between the in situ-converted total organic carbon (TOC) content and the vitrinite reflectance (Ro) of the shales and between the residual oil volume and the hydrocarbon yield were established. Second, the yields of residual oil and in situ-converted hydrocarbon were measured, revealing their sensitivity to fluid pressure and crude oil density. In addition, a model was proposed to estimate the amount of in situ-converted hydrocarbon based on TOC, hydrocarbon generation potential, Ro, residual oil volume, fluid pressure, and crude oil density. Finally, a method was established to determine key parameters of the final hydrocarbon yield from immature to low–moderate-maturity organic material during in situ conversion in shales. Following the procedure outlined in this paper, the estimated recoverable in situ-converted oil in the shales of the Nenjiang Formation in the Songliao Basin was estimated to be approximately 292 × 108 tons, along with 18.5 × 1012 cubic meters of natural gas, in an area of approximately 8 × 104 square kilometers. Collectively, the method developed in this study is independent of the organic matter type and other geological and/or petrophysical properties of the formation and can be applied to other areas globally where there are no available in situ conversion thermal simulation experimental data.

BackgroundIn randomized clinical trials (RCTs) investigating the application of transcranial alternating current stimulation (tACS) in schizophrenia, inconsistent results have been reported. The purpose of this exploratory systematic review of RCTs was to evaluate tACS as an adjunct treatment for patients with schizophrenia based on its therapeutic effects, tolerability, and safety.MethodsOur analysis included RCTs that evaluated adjunctive tACS’ effectiveness, tolerability, and safety in schizophrenia patients. Three independent authors extracted data and synthesized it using RevMan 5.3 software.ResultsThree RCTs involving 76 patients with schizophrenia were encompassed in the analysis, with 40 participants receiving active tACS and 36 receiving sham tACS. Our study revealed a significant superiority of active tACS over sham tACS in improving total psychopathology (standardized mean difference [SMD] = −0.61, 95% confidence interval [CI]: −1.12, −0.10; I2 = 16%, p = 0.02) and negative psychopathology (SMD = −0.65, 95% CI: −1.11, −0.18; I2 = 0%, p = 0.007) in schizophrenia. The two groups, however, showed no significant differences in positive psychopathology, general psychopathology, or auditory hallucinations (all p > 0.05). Two RCTs examined the neurocognitive effects of tACS, yielding varied findings. Both groups demonstrated similar rates of discontinuation due to any reason and adverse events (all p > 0.05).ConclusionAdjunctive tACS is promising as a viable approach for mitigating total and negative psychopathology in individuals diagnosed with schizophrenia. However, to gain a more comprehensive understanding of tACS’s therapeutic effects in schizophrenia, it is imperative to conduct extensive, meticulously planned, and well-documented RCTs.

Liver cancer is a huge global challenge. It has been exacerbated by tumor-associated dendritic cells (TDCs) due to Endoplasmic Reticulum (ER) stress. We planned to investigate the effects of LBP3 on TDCs immune function, and to explore whether the underlying mechanism was associated with IRE1α-XBP1 pathway of ER stress regulating lipid metabolism. In our early studies, LBP3 (40–350 kDa) with significant anti-tumor and immunomodulatory activities was isolated from the polysaccharide of Lycium barbarum L. (LBP). Here, we determined that LBP3 had a great anti-tumor efficacy in H22-tumor bearing mice by functional activation of TDCs. In vivo and in vitro results showed that LBP3 could up-regulate the expression of MHC Ⅱ, CD80 and CD86 on TDCs, increase the level of TNF-α secreted by TDCs, enhance TDCs’ ability to improve the proliferation and immunosuppression of lymphocytes. Furthermore, LBP3 could decrease the high expression of ER stress-related proteins IRE1α, GRP78, XBP1 and CHOP, reduce the lipid accumulation, raise the low expression of costimulatory molecules on TDCs induced by thapsigargin (TG). Taken together, LBP3 could reduce intracellular lipid accumulation by inhibiting IRE1α-XBP1 pathway of ER stress, improve the function of TDCs to stimulate T cells, thence play an anti-tumor role.

Staphylococcus aureus readily forms biofilms on host tissues and medical devices, enabling its persistence in chronic infections and resistance to antibiotic therapy. The accessory gene regulator (Agr) quorum sensing system plays a key role in regulating S. aureus biofilm formation. This study reveals the widely used fluoroquinolone antibiotic, ciprofloxacin, strongly stimulates biofilm formation in methicillin-resistant S. aureus, methicillin-sensitive S. aureus, and clinical isolates with diverse genetic backgrounds. Crystal violet staining indicated that ciprofloxacin induced a remarkable 12.46- to 15.19-fold increase in biofilm biomass. Confocal laser scanning microscopy revealed that ciprofloxacin induced denser biofilms. Phenotypic assays suggest that ciprofloxacin may enhance polysaccharide intercellular adhesin production, inhibit autolysis, and reduce proteolysis during the biofilm development, thus promoting initial adhesion and enhancing biofilm stability. Mechanistically, ciprofloxacin significantly alters the expression of various biofilm-related genes (icaA, icaD, fnbA, fnbB, eap, emp) and regulators (agrA, saeR). Gene knockout experiments revealed that deletion of agrC, rather than saeRS, abolishes the ciprofloxacin-induced enhancement of biofilm formation, underscoring the key role of agrC. Thermal shift assays showed ciprofloxacin binds purified AgrC protein, thereby inhibiting the Agr system. Molecular docking results further support the potential interaction between ciprofloxacin and AgrC. In summary, subinhibitory concentrations of ciprofloxacin stimulate S. aureus biofilm formation via an agrC-dependent pathway. This inductive effect may facilitate local infection establishment and bacterial persistence, ultimately leading to therapeutic failure.

IntroductionListeria monocytogenes is a globally distributed bacterium that exhibits genetic diversity and trait heterogeneity. The alternative sigma factor SigB serves as a crucial transcriptional regulator essential for responding to environmental stress conditions and facilitating host infection.MethodWe employed a comprehensive genetic analysis of sigB in a dataset comprising 46,921 L. monocytogenes genomes. The functional attributes of SigB were evaluated by phenotypic experiments.ResultsOur study revealed the presence of two predominant SigB factors (SigBT1 and SigBT2) in L. monocytogenes, with a robust correlation between SigBT1 and lineages I and III, as well as SigBT2 and lineage II. Furthermore, SigBT1 exhibits superior performance in promoting cellular invasion, cytotoxicity and enhancing biofilm formation and cold tolerance abilities under minimally defined media conditions compared to SigBT2.DiscussionThe functional characteristics of SigBT1 suggest a potential association with the epidemiology of lineages I and III strains in both human hosts and the natural environment. Our findings highlight the important role of distinct SigB factors in influencing the biological traits of L. monocytogenes of different lineages, thus highlighting its distinct pathogenic and adaptive attributes.

By the end of 2021, the pear yield in Xinjiang reached 1,795,900 tons, accounting for 1/9 of the country. Pear black spot, caused by Alternaria gaisen disease, has had a significant impact on the pear industry. A. gaisen can infect nearly all pear plants, resulting in black spots on the fruit that negatively affect both yield and quality. This study focused on the TRM76323 strain of Streptomyces, which was isolated from the soil of Tamarix chinensis in Xinjiang Province. Through a multiphase classification and identification method, the genetic classification status of the antagonistic strains was determined. The study also identified the antibacterial active components of streptochlorin using modern isolation and purification techniques. The antagonistic activity of Streptomyces against Alternaria was analyzed through in vitro and in vivo experiments. This research not only expanded the resource bank of antagonistic microorganisms in extreme environments in Xinjiang, but also identified active components that could contribute to the development of new drug lead compounds. Additionally, this study presents a novel approach for the prevention and control of pear black spot disease.