Development and antimicrobial activity of composite edible films of chitosan and nisin incorporated with perilla essential oil-glycerol monolaurate emulsions.

Aquatic products are highly susceptible to spoilage, and preparing composite edible film with essential oil is an effective solution. In this study, composite edible films were prepared using perilla essential oil (PEO)-glycerol monolaurate emulsions incorporated with chitosan and nisin, and the film formulation was optimized by response surface methodology. These films were applied to ready-to-eat fish balls and evaluated over a period of 12 days. The films with the highest inhibition rate against Staphylococcus aureus were acquired using a polymer composition of 6 µL/mL PEO, 18.4 µg/mL glycerol monolaurate, 14.2 mg/mL chitosan, and 11.0 µg/mL nisin. The fish balls coated with the optimal edible film showed minimal changes in appearance during storage and significantly reduced total bacterial counts and total volatile basic nitrogen compared to the control groups. This work indicated that the composite edible films containing essential oils possess ideal properties as antimicrobial packaging materials for aquatic foods.

Biologically Relevant Laminin-511 Moderates the Derivation and Proliferation of Human Lens Epithelial Stem/Progenitor-Like Cells.

Purpose: The role of specific extracellular matrix (ECM) molecules in lens cell development and regeneration is poorly understood, as appropriate cellular models are lacking. Here, a laminin-based lens cell in vitro induction system was developed to study the role of laminin in human lens epithelial stem/progenitor cell (LES/PC) development. Methods: The human embryonic stem cell-based lens induction system followed a three-stage protocol. The expression profile of laminins during lens induction was screened, and laminin-511 (LN511) was tested as a candidate substitute. LN511 induction system cellular and molecular features, including induction efficiency, transcription factor expression related to different lens development stages, ECM alterations, and Hippo/YAP signaling, were evaluated. Results: LAMA5, LAMB1, and LAMC1 were highly expressed around the time of LES/PC derivation. We chose LN511 (product of LAMA5, LAMB1, and LAMC1) and found that it considerably enhanced lens cell induction efficiency, compared to that in Matrigel-coated culture, as more and larger lentoid bodies were detected. Notably, LES/PC induction efficiency improved by promoting lens specification-related transcription factor expression and cell proliferation. Transcriptome analysis revealed that compared to those with Matrigel, ECM accumulation and cell adhesion were downregulated in the LN511 system. Hippo/YAP signaling was hypoactive during LES/P-like cell generation, and small molecule inhibitors of YAP/TAZ activity upregulated LES/PC marker expression and promoted the efficiency of LES/P-like cell derivation. Conclusions: The laminin isoform LN511 is a reliable substitute for the LES/P-like cell induction system, and LN511-YAP acted as efficient modulators of LES/PC derivation; this contributes to knowledge of the role of the ECM in human lens development.

Prevalence and molecular characteristics of intestinal pathogenic Escherichia coli isolated from diarrheal pigs in Southern China.

Intestinal pathogenic Escherichia coli (InPEC) is one of the most common causes of bacterial diarrhea in farm animals, including profuse neonatal diarrhea and post weaning diarrhea (PWD) in piglets. In this study, we investigated the prevalence of InPEC and associated primary virulence factors among 543 non-duplicate E. coli isolates from diarrheal pigs from 15 swine farms in southern China. Six major virulence genes associated with InPEC were identified among 69 (12.71 %) E. coli isolates and included est (6.62 %), K88 (4.79 %), elt (3.68 %), eae (1.47 %), stx2 (0.92 %) and F18 (0.55 %). Three pathotypes of InPEC were identified including ETEC (8.10 %), EPEC (1.29 %) and STEC/ETEC (0.92 %). In particular, K88 was only found in ETEC from breeding farms, whereas F18 was only present in STEC/ETEC hybrid from finishing farms. Whole genome sequence analysis of 37 E. coli isolates revealed that InPEC strains frequently co-carried multiple antibiotic resistance gene (ARG). est, elt and F18 were also found to co-locate with ARGs on a single IncFIB/IncFII plasmid. InPEC isolates from different pathotypes also possessed different profiles of virulence genes and antimicrobial resistance genes. Population structure analysis demonstrated that InPEC isolates from different pathotypes were highly heterogeneous whereas those of the same pathotype were extremely similar. Plasmid analysis revealed that K88 and/or est/elt were found on pGX18-2-like/pGX203-2-like and pGX203-1-like IncFII plasmids, while F18 and elt/est, as well as diverse ARGs were found to co-locate on IncFII/IncFIB plasmids with a non-typical backbone. Moreover, these key virulence genes were flanked by or adjacent to IS elements. Our findings indicated that both clonal expansion and horizontal spread of epidemic IncFII plasmids contributed to the prevalence of InPEC and the specific virulence genes (F4, F18, elt and est) in the tested swine farms.

miR-107 reverses the multidrug resistance of gastric cancer by targeting the CGA/EGFR/GATA2 positive feedback circuit.

Chemotherapy is still the main therapeutic strategy for gastric cancer (GC). However, most patients eventually acquire multidrug resistance (MDR). Hyperactivation of the EGFR signaling pathway contributes to MDR by promoting cancer cell proliferation and inhibiting apoptosis. We previously identified the secreted protein CGA as a novel ligand of EGFR and revealed a CGA/EGFR/GATA2 positive feedback circuit that confers MDR in GC. Herein, we outline a microRNA-based treatment approach for MDR reversal that targets both CGA and GATA2. We observed increased expression of CGA and GATA2 and increased activation of EGFR in GC samples. Bioinformatic analysis revealed that miR-107 could simultaneously target CGA and GATA2, and the low expression of miR-107 was correlated with poor prognosis in GC patients. The direct interactions between miR-107 and CGA or GATA2 were validated by luciferase reporter assays and Western blot analysis. Overexpression of miR-107 in MDR GC cells increased their susceptibility to chemotherapeutic agents, including fluorouracil, adriamycin, and vincristine, in vitro. Notably, intratumor injection of the miR-107 prodrug enhanced MDR xenograft sensitivity to chemotherapies in vivo. Molecularly, targeting CGA and GATA2 with miR-107 inhibited EGFR downstream signaling, as evidenced by the reduced phosphorylation of ERK and AKT. These results suggest that miR-107 may contribute to the development of a promising therapeutic approach for the treatment of MDR in GC.

Progress in clinical diagnosis and treatment of colorectal cancer with rare genetic variants.

Targeted therapy is crucial for advanced colorectal cancer (CRC) positive for genetic drivers. With advances in deep sequencing technology and new targeted drugs, existing standard molecular pathological detection systems and therapeutic strategies can no longer meet the requirements for careful management of patients with advanced CRC. Thus, rare genetic variations require diagnosis and targeted therapy in clinical practice. Rare gene mutations, amplifications, and rearrangements are usually associated with poor prognosis and poor response to conventional therapy. This review summarizes the clinical diagnosis and treatment of rare genetic variations, in genes including erb-b2 receptor tyrosine kinase 2 (ERBB2), B-Raf proto-oncogene, serine/threonine kinase (BRAF), ALK receptor tyrosine kinase/ROS proto-oncogene 1, receptor tyrosine kinase (ALK/ROS1), neurotrophic receptor tyrosine kinases (NTRKs), ret proto-oncogene (RET), fibroblast growth factor receptor 2 (FGFR2), and epidermal growth factor receptor (EGFR), to enhance understanding and identify more accurate personalized treatments for patients with rare genetic variations.

Association of immune checkpoint inhibitors with SARS-CoV-2 infection rate and prognosis in patients with solid tumors: a systematic review and meta-analysis.

The rate and prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with solid cancer tumors actively treated with immune checkpoint inhibitors (ICIs) have not been fully determined. The goal of this meta-analysis was to explore this issue, which can be helpful to clinicians in their decision-making concerning patient treatment. We conducted a thorough search for relevant cohort studies in the databases PubMed, Embase, Cochrane Library, and Web of Science. Mortality and infection rate were the primary endpoints, and the incidence of severe or critical disease was the secondary result. A total of 6,267 cases (individual patients) were represented in 15 studies. Prior exposure to ICIs was not correlated with an elevated risk of SARS-CoV-2 infection (relative risk (RR) 1.04, 95% CI 0.57-1.88, z = 0.12, P = 0.905) or mortality (RR 1.22, 95% CI 0.99-1.50, z = 1.90, P = 0.057). However, the results of the meta-analysis revealed that taking ICIs before SARS-CoV-2 diagnosis increased the chance of developing severe or critical disease (RR 1.51, 95% CI 1.09-2.10, z = 2.46, P = 0.014). No significant inter-study heterogeneity was observed. The infection and mortality rates of SARS-CoV-2 in patients with solid tumors who previously received ICIs or other antitumor therapies did not differ significantly. However, secondary outcomes showed that ICIs treatment before the diagnosis of SARS-CoV-2 infection was significantly associated with the probability of severe or critical illness. Systematic review registration: https://www.crd.york.ac.uk/prospero/#recordDetails PROSPERO, identifier CRD42023393511.

Shootin1 Regulates Retinal Ganglion Cell Neurite Development: Insights From an RGC Direct Somatic Cell Reprogramming Model.

Purpose: Retinal ganglion cells (RGCs) connect the retina to the brain. Proper development of the axons and dendrites of RGCs is the basis for these cells to function as projection neurons to deliver visual information to the brain. The purpose of this study was to investigate the function of Shtn1 (which encodes shootin1) in RGC neurite development. Methods: Immunofluorescence (IF) was used to characterize the expression pattern of marker genes. An in vitro direct somatic cell reprogramming system was used to generate RGC-like neurons (iRGCs), which was subsequently used to study the function of Shtn1. Short-hairpin RNAs (shRNAs) were used to knock down Shtn1, and the coding sequence (CDS) of Shtn1 was used to overexpress the gene. Lentiviruses were used to deliver shRNAs or CDSs into iRGCs. The patch clamp technique was used to measure the electrophysiological properties of the iRGCs. RNA sequencing (RNA-seq) was used to examine transcriptome expression. Results: Using IF, we demonstrated that shootin1 is distinctively expressed in RGCs during the period in which RGCs actively develop and adjust the connections of their neurites with upstream and downstream neurons. Using the iRGC system, we demonstrated that Shtn1 promotes the growth and complexity of neurites and thus the electrophysiological maturation, of iRGCs. RNA-seq analyses showed that Shtn1 may also regulate gene expression and neurogenesis in iRGCs. Conclusions: Shtn1 promotes RGC neurite development. These findings improve our understanding of the molecular machinery governing RGC neurite development and may help to optimize future RGC regeneration methods.

Ligand-Induced Electronic Structure Modulation of Self-Evolved Ni3S2 Nanosheets for the Electrocatalytic Oxygen Evolution Reaction.

Modulating the electronic structure of the electrocatalyst plays a vital role in boosting the electrocatalytic performance of the oxygen evolution reaction (OER). In this work, we introduced a one-step solvothermal method to fabricate 1,1-ferrocene dicarboxylic acid (FcDA)-decorated self-evolved nickel sulfide (Ni3S2) nanosheet arrays on a nickel foam (NF) framework (denoted as FcDA-Ni3S2/NF). Benefiting from the interconnected ultrathin nanosheet architecture, ligand dopants induced and facilitated in situ structural reconstruction, and the FcDA-decorated Ni3S2 (FcDA-Ni3S2/NF) outperformed its singly doped and undoped counterparts in terms of OER activity. The optimized FcDA-Ni3S2/NF self-supported electrode presents a remarkably low overpotential of 268 mV to achieve a current density of 10 mA cm-2 for the OER and demonstrates robust electrochemical stability for 48 h in a 1.0 M KOH electrolyte. More importantly, in situ electrochemical Raman spectroscopy reveals the generation of catalytically active oxyhydroxide species (NiOOH) derived from the surface construction during the OER of pristine FcDA-Ni3S2/NF, contributing significantly to its superior electrocatalytic performance. This study concerns the modulation of electronic structure through ligand engineering and may provide profound insight into the design of cost-efficient OER electrocatalysts.

Phloretin inhibits transmissible gastroenteritis virus proliferation via multiple mechanisms.

Transmissible gastroenteritis virus (TGEV), an enteropathogenic coronavirus, has caused huge economic losses to the pig industry, with 100% mortality in piglets aged 2 weeks and intestinal injury in pigs of other ages. However, there is still a shortage of safe and effective anti-TGEV drugs in clinics. In this study, phloretin, a naturally occurring dihydrochalcone glycoside, was identified as a potent antagonist of TGEV. Specifically, we found phloretin effectively inhibited TGEV proliferation in PK-15 cells, dose-dependently reducing the expression of TGEV N protein, mRNA, and virus titer. The anti-TGEV activity of phloretin was furthermore refined to target the internalization and replication stages. Moreover, we also found that phloretin could decrease the expression levels of proinflammatory cytokines induced by TGEV infection. In addition, we expanded the potential key targets associated with the anti-TGEV effect of phloretin to AR, CDK2, INS, ESR1, ESR2, EGFR, PGR, PPARG, PRKACA, and MAPK14 with the help of network pharmacology and molecular docking techniques. Furthermore, resistant viruses have been selected by culturing TGEV with increasing concentrations of phloretin. Resistance mutations were reproducibly mapped to the residue (S242) of main protease (Mpro). Molecular docking analysis showed that the mutation (S242F) significantly disrupted phloretin binding to Mpro, suggesting Mpro might be a potent target of phloretin. In summary, our findings indicate that phloretin is a promising drug candidate for combating TGEV, which may be helpful for developing pharmacotherapies for TGEV and other coronavirus infections.

Microplastics footprint in nature reserves-a case study on the microplastics in the guano from Yancheng Wetland Rare Birds National Nature Reserve, China.

Bio-ingestion of microplastics poses a global threat to ecosystems, yet studies within nature reserves, crucial habitats for birds, remain scarce despite the well-documented ingestion of microplastics by avian species. Located in Jiangsu Province, China, the Yancheng Wetland Rare Birds Nature Reserve is home to diverse bird species, including many rare ones. This study aimed to assess the abundance and characteristics of microplastics in common bird species within the reserve, investigate microplastic enrichment across different species, and establish links between birds' habitat types and microplastic ingestion. Microplastics were extracted from the feces of 110 birds, with 84 particles identified from 37.27% of samples. Among 8 species studied, the average microplastic abundance ranged from 0.97 ± 0.47 to 43.43 ± 61.98 items per gram of feces, or 1.5 ± 0.87 to 3.4 ± 1.50 items per individual. The Swan goose (Anser cygnoides) exhibited the highest microplastic abundance per gram of feces, while the black-billed gull (Larus saundersi) had the highest abundance per individual. The predominant form of ingested microplastics among birds in the reserve was fibers, with polyethylene being the most common polymer type. Significant variations in plastic exposure were observed among species and between aquatic and terrestrial birds. This study represents the first quantitative assessment of microplastic concentrations in birds within the reserve, filling a crucial gap in research and providing insights for assessing microplastic pollution and guiding bird conservation efforts in aquatic and terrestrial environments.

Cancer SLC6A6-mediated taurine uptake transactivates immune checkpoint genes and induces exhaustion in CD8+ T cells.

Taurine is used to bolster immunity, but its effects on antitumor immunity are unclear. Here, we report that cancer-related taurine consumption causes T cell exhaustion and tumor progression. The taurine transporter SLC6A6 is correlated with aggressiveness and poor outcomes in multiple cancers. SLC6A6-mediated taurine uptake promotes the malignant behaviors of tumor cells but also increases the survival and effector function of CD8+ T cells. Tumor cells outcompete CD8+ T cells for taurine by overexpressing SLC6A6, which induces T cell death and malfunction, thereby fueling tumor progression. Mechanistically, taurine deficiency in CD8+ T cells increases ER stress, promoting ATF4 transcription in a PERK-JAK1-STAT3 signaling-dependent manner. Increased ATF4 transactivates multiple immune checkpoint genes and induces T cell exhaustion. In gastric cancer, we identify a chemotherapy-induced SP1-SLC6A6 regulatory axis. Our findings suggest that tumoral-SLC6A6-mediated taurine deficiency promotes immune evasion and that taurine supplementation reinvigorates exhausted CD8+ T cells and increases the efficacy of cancer therapies.

Network pharmacology and molecular docking to explore the mechanism of a clinical proved recipe for external use of clearing heat and removing dampness in the treatment of immune-related cutaneous adverse events.

Immune-related cutaneous adverse events (ircAEs) will undermine the patients' quality of lives, and interrupt the antitumor therapy. A clinical proved recipe for external use of clearing heat and removing dampness (Qing-Re-Li-Shi Formula, hereinafter referred to as "QRLSF") is beneficial to the treatment of ircAEs in clinical practice. Our study will elucidate the mechanism of QRLSF against ircAEs based on network pharmacology and molecular docking. The active components and corresponding targets of QRLSF were collected through traditional Chinese medicine systems pharmacology database. GeneCards, online Mendelian inheritance in man, and pharmacogenomics knowledgebase were used to screen the targets of ircAEs. The intersecting targets between drug and disease were acquired by venn analysis. Cytoscape software was employed to construct "components-targets" network. Search tool for the retrieval of interacting genes/proteins database was applied to establish the protein-protein interaction network and then its core targets were identified. Gene ontology and Kyoto encyclopedia of genes and genomes analysis was performed to predict the mechanism. The molecular docking verification of key targets and related phytomolecules was accomplished by AutoDock Vina software. Thirty-nine intersecting targets related to QRLSF against ircAEs were recognized. The analysis of network clarified 5 core targets (STAT3, RELA, TNF, TP53, and NFKBIA) and 4 key components (quercetin, apigenin, luteolin, and ursolic acid). The activity of QRLSF against ircAEs could be attributed to the regulation of multiple biological effects via multi-pathways (PI3K-Akt pathway, cytokine-cytokine receptor interaction, JAK-STAT pathway, chemokine pathway, Th17 cell differentiation, IL-17 pathway, TNF pathway, and Toll-like receptor pathway). The binding activities were estimated as good level by molecular docking. These discoveries disclosed the multi-component, multi-target, and multi-pathway characteristics of QRLSF against ircAEs, providing a new strategy for such medical problem.

Advances in the study of the correlation between insulin resistance and infertility.

This is a narrative review of the progress of research on the correlation between insulin resistance and infertility. Insulin resistance (IR) is not only involved in the development of various metabolic diseases, but also affects female reproductive function, and to some extent is closely related to female infertility. IR may increase the risk of female infertility by activating oxidative stress, interfering with energy metabolism, affecting oocyte development, embryo quality and endometrial tolerance, affecting hormone secretion and embryo implantation, as well as affecting assisted conception outcomes in infertile populations and reducing the success rate of assisted reproductive technology treatment in infertile populations. In addition, IR is closely associated with spontaneous abortion, gestational diabetes and other adverse pregnancies, and if not corrected in time, may increase the risk of obesity and metabolic diseases in the offspring in the long term. This article provides a review of the relationship between IR and infertility to provide new ideas for the treatment of infertility.

Clinical Experience of External Application of Clearing Heat and Removing Dampness in Relieving Grade 2 to 3 Rash Caused by Programed Cell Death Protein 1 (PD-1)/Programed Cell Death Ligand 1 (PD-L1) Inhibitors: A Single-Center Retrospective Study.

OBJECTIVE: In China, grade 2 to 3 immune-related rash will probably lead to the interruption of immunotherapy. Corticosteroid (CS) is the main treatment, but not always effective. The external application of clearing heat and removing dampness, which is represented by Qing-Re-Li-Shi Formula (QRLSF), has been used in our hospital to treat immune-related cutaneous adverse events (ircAEs) for the last 5 years. The purpose of this study was to discuss its efficacy and safety in the treatment of grade 2 to 3 rash. METHODS: A retrospective study of patients with grade 2 to 3 immune-related rash in our hospital from December 2019 to December 2022 was conducted. These patients received QRLSF treatment. Clinical characteristics, treatment outcome, and health-related quality of life (HrQoL) were analyzed. RESULTS: Thirty patients with grade 2 to 3 rash (median onset time: 64.5 days) were included. The skin lesions of 24 cases (80%) returned to grade 1 with a median time of 8 days. The accompanying symptoms were also improved with median time of 3 to 4 days. The addition of antihistamine (AH) drug didn't increase the efficacy of QRLSF (AH + QRLSF: 75.00% vs QRLSF: 83.33%, P = .66). No significant difference was observed in the efficacy of QRLSF treatment regardless of whether patients had previously received CS therapy (untreated population: 88.24% vs treated population: 69.23%, P = .36). During 1-month follow-up, 2 cases (8.33%) underwent relapses. In terms of HrQoL, QRLSF treatment could significantly reduce the median scores of all domains of Skindex-16, including symptoms (39.58 vs 8.33, P < .0001), emotions (58.33 vs 15.48, P < .0001), functioning (46.67 vs 13.33, P < .0001) and composite (52.60 vs 14.06, P < .0001). CONCLUSION: External application of clearing heat and removing dampness was proven to be an effective and safe treatment for such patients. In the future, high-quality trials are required to determine its clinical application in the field of ircAEs.

Retinal Ganglion Cell Fate Induction by Ngn-Family Transcription Factors.

Purpose: Retinal ganglion cells (RGCs) are the projection neurons of the retina. Loss of RGCs is the cellular basis for vision loss in patients with glaucoma. Finding ways to regenerate RGCs will aid in the development of regenerative therapies for patients with glaucoma. The aim of this study was to examine the ability of Ngn-family transcription factors (TFs) to induce RGC regeneration through reprogramming in vitro and in vivo. Methods: In vitro, lentiviruses were used to deliver Ngn-TFs into mouse embryonic fibroblasts (MEFs). In vivo, mouse pup retina electroporation was used to deliver Ngn-TFs into late-stage retinal progenitor cells (RPCs). Immunofluorescence staining and RNA sequencing were used to examine cell fate reprogramming; patch-clamp recording was used to examine neuronal electrophysiologic functions. Results: In vitro, all three Ngn-TFs, Ngn1, Ngn2, and Ngn3, were able to work alone to reprogram MEFs into RGC-like neurons that resembled RGCs at the transcriptome level, exhibited typical neuronal membrane electrophysiologic properties, and formed functional synaptic communications with retinal neurons. In vivo, Ngn-TFs reprogrammed the differentiation-competent state of late-stage RPCs to generate RGCs. Conclusions: Ngn-TFs are effective in inducing an RGC-like fate both in vitro and in vivo and might be explored further in the future for glaucoma translational applications.

Enzyme-catalyzed electrochemical aptasensor for ultrasensitive detection of soluble PD-L1 in breast cancer based on decorated covalent organic frameworks and carbon nanotubes.

BACKGROUND: Soluble programmed death-ligand 1 (sPD-L1) is critically involved in breast cancer recurrence and metastasis. However, the clinical application of highly sensitive sPD-L1 assays remains a challenge due to its low abundance in peripheral blood. To address this issue, for the first time, an enzyme-catalyzed electrochemical aptasensing platform was devised, incorporating covalent organic frameworks-gold nanoparticles-antibody-horseradish peroxidase (COFs-AuNPs-Ab-HRP) and polyethyleneimine-functionalized multiwalled carbon nanotubes (MWCNTs-PEI-AuNPs) for the highly specific and ultrasensitive detection of sPD-L1. RESULTS: MWCNTs-PEI-AuNPs possessed an extensive specific surface area and exhibited excellent electrical conductivity, facilitating the immobilization of aptamer and amplifying the signal. COFs modified with AuNPs not only amplified the electrical signal but also proffered a loading platform for the Ab and HRP. The favorable biocompatibility of COFs contributed to the preservation of enzyme activity and stability. HRP acted in synergy with hydrogen peroxide (H2O2) to catalyze the oxidation of hydroquinone (HQ) to benzoquinone (BQ). Subsequently, BQ underwent electrochemical reduction to HQ, inducing an enzymatic redox cycle that amplified the electrochemical signal and enhanced the sensitivity and selectivity of the detection method. The developed aptasensor displayed a liner range for sPD-L1 identification from 1 pg mL-1 to 100 ng mL-1 and the detection limit reached 0.143 pg mL-1 (S/N = 3). SIGNIFICANCE: Paving the way for clinical application, this strategy detected differences in sPD-L1 in cell supernatants and peripheral blood of breast cancer patients with higher sensitivity compared to commercial sPD-L1 ELISA kit. This work demonstrates significant potential in offering reference information for early diagnosis and disease surveillance of breast cancer.

Generating Retinas through Guided Pluripotent Stem Cell Differentiation and Direct Somatic Cell Reprogramming.

Retinal degeneration diseases affect millions of people worldwide but are among the most difficult eye diseases to cure. Studying the mechanisms and developing new therapies for these blinding diseases requires researchers to have access to many retinal cells. In recent years there has been substantial advances in the field of biotechnology in generating retinal cells and even tissues in vitro, either through programmed sequential stem cell differentiation or direct somatic cell lineage reprogramming. The resemblance of these in vitro-generated retinal cells to native cells has been increasingly utilized by researchers. With the help of these in vitro retinal models, we now have a better understanding of human retinas and retinal diseases. Furthermore, these in vitro-generated retinal cells can be used as donor cells which solves a major hurdle in the development of cell replacement therapy for retinal degeneration diseases, while providing a promising option for patients suffering from these diseases. In this review, we summarize the development of pluripotent stem cell-to-retinal cell differentiation methods, the recent advances in generating retinal cells through direct somatic cell reprogramming, and the translational applications of retinal cells generated in vitro. Finally, we discuss the limitations of the current protocols and possible future directions for improvement.

The epidemiological characteristics and infection risk factors for extrapulmonary tuberculosis in patients hospitalized with pulmonary tuberculosis infection in China from 2017 to 2021.

BACKGROUND: Pulmonary tuberculosis (PTB) complicated with extrapulmonary tuberculosis (EPTB) infection can aggravate the disease, but there have been few reports. METHODS: Retrospective analysis was used to collect the clinical data of PTB patients with pathogen positive in a teaching hospital from 2017 to 2021. We describe the incidence, the invasive site of EPTB patients, and analyze the infection risk factors for PTB with EPTB by univariate and multivariate logistic regression models. We also compared the complications, disease burden with chi-square test and rank-sum test. RESULTS: A total of 1806 PTB were included, of which 263 (14.6%) were complicated with EPTB. The common invasive sites for EPTB were neck lymph nodes (16.49%), intestines (16.13%), and meninges (10.75%). Age ≤ 40 (OR = 1.735; 95%CI [1.267-2.376]; P = 0.001), malnutrition (OR = 2.029; 95%CI [1.097-3.753]; P = 0.022), anemia (OR = 1.739; 95%CI[1.127-2.683]; P = 0.012), and osteoporosis (OR = 4.147; 95%CI [1.577-10.905]; P = 0.004) were all independent risk factors for PTB infection with EPTB. The incidence of extrathoracic hydrothorax, intestinal bacterial infection, urinary tract bacterial infection, and abdominal bacterial infection were higher in patients with PTB with EPTB. PTB with EPTB patients also had longer median hospitalization durations (19 vs. 14 days), during which time they incurred higher total costs, laboratory test costs, imaging examination costs, and drug use costs. CONCLUSION: This study found important risk factors for PTB complicated with EPTB, such as age ≤ 40, malnutrition, anemia, and osteoporosis. PTB with EPTB patients have more extrapulmonary complications and higher hospitalization disease burden.

Potential impact of time trend of whole grain intake on burden of major cancers in China.

Numerous studies have revealed associations between high intake of whole grains and reduced risk of various cancers. Yet, in recent decades, the traditional Chinese diets have been challenged by reduction in whole grains and increase in refined grains. To assess the impact of this dietary transition on cancer prevention, we analyzed the time trend of whole grain intake using nationally representative sampling data of over 15 thousand individuals from the China Health and Nutrition Survey. We applied the comparative risk assessment method to estimate the population attributable fraction of cancers due to insufficient whole grain intake from 1997 to 2011 and projected the trend of whole grain intake and the associated burden of cancers to 2035. We found a significant decrease of approximately 59% of whole grain intake in the Chinese population from 1997 to 2011. Compared with 1997, insufficient intake of whole grains was responsible for 9940 more cases of breast cancer, 12,903 more cases of colorectal cancer and 434 more cases of pancreatic cancer in 2011. Our projections suggest that if every Chinese would consume 125 g whole grain per day as recommended by the latest Chinese Dietary Guidelines, 0.63% bladder cancer, 8.98% breast cancer, 15.85% colorectal cancer, 3.86% esophageal cancer, 2.52% liver cancer and 2.22% pancreatic cancer (totaling 186,659 incident cases) could theoretically be averted by 2035. Even if everyone maintained the 2011 whole grain intake level, an estimated 8.38% of cancer events could still be prevented by 2035.

Structure Property Relationship of Micellar Waterborne Poly(Urethane-Urea): Tunable Mechanical Properties and Controlled Release Profiles with Amphiphilic Triblock Copolymers.

Waterborne polyurethane (WPU) has attracted significant interest as a promising alternative to solvent-based polyurethane (SPU) due to its positive impact on safety and sustainability. However, significant limitations of WPU, such as its weaker mechanical strength, limit its ability to replace SPU. Triblock amphiphilic diols are promising materials to enhance the performance of WPU due to their well-defined hydrophobic-hydrophilic structures. Yet, our understanding of the relationship between the hydrophobic-hydrophilic arrangements of triblock amphiphilic diols and the physical properties of WPU remains limited. In this study, we show that by controlling the micellar structure of WPU in aqueous solution via the introduction of triblock amphiphilic diols, the postcuring efficiency and the resulting mechanical strength of WPU can be significantly enhanced. Small-angle neutron scattering confirmed the microstructure and spatial distribution of hydrophilic and hydrophobic segments in the engineered WPU micelles. In addition, we show that the control of the WPU micellar structure through triblock amphiphilic diols renders WPU attractive in the applications of controlled release, such as drug delivery. Here, curcumin was used as a model hydrophobic drug, and the drug release behavior from WPU-micellar-based drug delivery systems was characterized. It was found that curcumin-loaded WPU drug delivery systems were highly biocompatible and exhibited antibacterial properties in vitro. Furthermore, the sustained release profile of the drug was found to be dependent on the structure of the triblock amphiphilic diols, suggesting the possibility of controlling the drug release profile via the selection of triblock amphiphilic diols. This work shows that by shedding light on the structure-property relationship of triblock amphiphilic diol-containing WPU micelles, we may enhance the applicability of WPU systems and move closer to realizing their promising potential in real-life applications.