Discovery of interspecific alloparental care of silver-eared mesia nestlings by a mountain bulbul.

Although brood parasitism has been well documented among bird species, interspecific alloparenting, which is parenting behavior of adult individuals of one species toward the progeny of another species, is increasingly being reported. However, compared with the many reports of interspecific alloparenting behavior in North America and Europe, this phenomenon is less well known in China, with only two prior cases of interspecific alloparenting behavior in birds having been recorded. On June 23, 2022, we observed an instance of interspecific alloparental care provided by a mountain bulbul (Ixos mcclellandii) towards silver-eared mesia (Leiothrix argentauris) nestlings in Caihu Village, Jingdong County, Yunnan Province, southwestern China. We recorded 19.5 h of footage during the period in which the mountain bulbul provided care for the nestlings with the aim of documenting detailed observations of interspecific alloparenting to contribute to our overall understanding of this behavior. The alloparenting behavior of the mountain bulbul lasted for at least 5 days. During this period, both silver-eared mesia parents fed their nestlings 157 times and removed their nestlings' fecal sacs 5 times, while the mountain bulbul fed the nestlings 30 times and removed the nestlings' fecal sacs 4 times. In addition, the male silver-eared mesia parent chased the mountain bulbul away during nestling feeding. As there was no life history information for the mountain bulbul at that time, we were unable to directly determine why it exhibited interspecific alloparental care. Regardless of the reason for the mountain bulbul's behavior, these findings provide valuable information for future studies on the reproductive ecology of these two bird species.

Fine-tuning of liposome integrity for differentiated transcytosis and enhanced antitumor efficacy.

Transcytosis-inducing nanomedicines have been developed to improve tumor extravasation. However, the fate during transcytosis across multicell layers and the structural integrity of the nanomedicines before reaching tumor cells could impact antitumor therapy. Here, a BAY 87-2243 (a hypoxia-inducible factor-1 inhibitor)-loaded liposomal system (HA-P-LBAY) modified by low molecular weight protamine (LMWP) and crosslinked by hyaluronic acid (HA) was constructed. This system could accomplish differentiate cellular transport in endothelial and tumor cells by fine-tuning its structural integrity, i.e. transcytosis across the endothelial cells while preserving structural integrity, facilitating subsequent retention and drug release within tumor cells via degradation-induced aggregation. In vitro cellular uptake and transwell studies demonstrated that HA-P-LBAY were internalized by endothelial cells (bEnd.3) via an active, caveolin and heparin sulfate proteoglycan (HSPG)-mediated endocytosis, and subsequently achieved transcytosis mainly through the ER/Golgi pathway. Moreover, the fluorescence resonance energy transfer (FRET) study showed that HA-crosslinking maintained higher integrity of HA-P-LBAY after transcytosis, more efficiently than electrostatic coating of HA (HA/P-LBAY). In addition, more HA-P-LBAY was retained in tumor cells (4T1) compared to HA/P-LBAY corresponding to its enhanced in vitro cytotoxicity. This may be attributed to better integrity of HA-P-LBAY post endothelial transcytosis and more degradation of HA in tumor cells, leading to more liposome aggregation and inhibition of their transcytosis, which was inferred by both TEM images and the HAase responsiveness assay proved by FRET. In vivo, HA-P-LBAY exhibited more potency in tumor suppression than the other formulations in both low and high permeability tumor models. This highlighted that fine-tuning of structural integrity of nanocarriers played a key role no matter whether the transcytosis of nanocarriers contributed to cellular transport. Collectively, this study provides a promising strategy for antitumor therapies by fine-tuning liposome integrity to achieve active trans-endothelial transport with structural integrity and selective aggregation for prolonged tumor retention.

Effective in vivo reactivation of HIV-1 latency reservoir via oral administration of EK-16A-SNEDDS.

The latent reservoir of human immunodeficiency virus (HIV) is a major obstacle in the treatment of acquired immune deficiency syndrome (AIDS). The "shock and kill" strategy has emerged as a promising approach for clearing HIV latent reservoirs. However, current latency-reversing agents (LRAs) have limitations in effectively and safely activating the latent virus and reducing the HIV latent reservoirs in clinical practice. Previously, EK-16A was extracted from Euphorbia kansui, which had the effect of interfering with the HIV-1 latent reservoir and inhibiting HIV-1 entry. Nevertheless, there is no suitable and efficient EK-16A oral formulation for in vivo delivery and clinical use. In this study, an oral EK-16A self-nanoemulsifying drug delivery system (EK-16A-SNEDDS) was proposed to "shock" the HIV-1 latent reservoir. This system aims to enhance the bioavailability and delivery of EK-16A to various organs. The composition of EK-16A-SNEDDS was optimized through self-emulsifying grading and ternary phase diagram tests. Cell models, pharmacokinetic experiments, and pharmacodynamics in HIV-1 latent cell transplant animal models suggested that EK-16A-SNEDDS could be absorbed by the gastrointestinal tract and enter the blood circulation after oral administration, thereby reaching various organs to activate latent HIV-1. The prepared EK-16A-SNEDDS demonstrated safety and efficacy, exhibited high clinical experimental potential, and may be a promising oral preparation for eliminating HIV-1 latent reservoirs.

Hair Follicle-Targeted Delivery of Azelaic Acid Micro/Nanocrystals Promote the Treatment of Acne Vulgaris.

Purpose: Acne vulgaris is a chronic inflammatory skin disorder centered on hair follicles, making hair follicle-targeted delivery of anti-acne drugs a promising option for acne treatment. However, current researches have only focused on the delivering to healthy hair follicles, which are intrinsically different from pathologically clogged hair follicles in acne vulgaris. Patients and Methods: Azelaic acid (AZA) micro/nanocrystals with different particle sizes were prepared by wet media milling or high-pressure homogenization. An experiment on AZA micro/nanocrystals delivering to healthy hair follicles was carried out, with and without the use of physical enhancement techniques. More importantly, it innovatively designed an experiment, which could reveal the ability of AZA micro/nanocrystals to penetrate the constructed clogged hair follicles. The anti-inflammatory and antibacterial effects of AZA micro/nanocrystals were evaluated in vitro using a RAW264.7 cell model stimulated by lipopolysaccharide and a Cutibacterium acnes model. Finally, both the anti-acne effects and skin safety of AZA micro/nanocrystals and commercial products were compared in vivo. Results: In comparison to commercial products, 200 nm and 500 nm AZA micro/nanocrystals exhibited an increased capacity to target hair follicles. In the combination group of AZA micro/nanocrystals and ultrasound, the ability to penetrate hair follicles was further remarkably enhanced (ER value up to 9.6). However, toward the clogged hair follicles, AZA micro/nanocrystals cannot easily penetrate into by themselves. Only with the help of 1% salicylic acid, AZA micro/nanocrystals had a great potential to penetrate clogged hair follicle. It was also shown that AZA micro/nanocrystals had anti-inflammatory and antibacterial effects by inhibiting pro-inflammatory factors and Cutibacterium acnes. Compared with commercial products, the combination of AZA micro/nanocrystals and ultrasound exhibited an obvious advantage in both skin safety and in vivo anti-acne therapeutic efficacy. Conclusion: Hair follicle-targeted delivery of AZA micro/nanocrystals provided a satisfactory alternative in promoting the treatment of acne vulgaris.

Traditional Chinese medicine for post-viral olfactory dysfunction: A systematic review.

Background: Post-viral olfactory dysfunction (PVOD) is the common symptoms of long COVID, lacking of effective treatments. Traditional Chinese medicine (TCM) is claimed to be effective in treating olfactory dysfunction, but the evidence has not yet been critically appraised. We conducted a systematic review to evaluate the effectiveness and safety of TCM for PVOD. Methods: We searched eight databases to identified clinical controlled studies about TCM for PVOD. The Cochrane risk of bias tools and GRADE were used to evaluate the quality of evidence. Risk ratio (RR), mean differences (MD), and 95 % confidence interval (CI), were used for effect estimation and RevMan 5.4.1 was used for data analysis. Results: Six randomized controlled trials (RCTs) (545 participants), two non-randomized controlled trials (non-RCTs) (112 participants), and one retrospective cohort study (30 participants) were included. The overall quality of included studies was low. Acupuncture (n = 8) and acupoint injection (n = 3) were the mainly used TCM therapies. Five RCTs showed a better effect in TCM group. Four trials used acupuncture, and three trials used acupoint injection. The results of two non-RCTs and one cohort study were not statistically significant. Two trials reported mild to moderate adverse events (pain and brief syncope caused by acupuncture or acupoint injection). Conclusions: Limited evidence focus on acupuncture and acupoint injection for PVOD and suggests that acupuncture and acupoint injection may be effective in improving PVOD. More well-designed trials should focus on acupuncture to confirm the benefit. Protocol registration: The protocol of this review was registered at PROSPERO: CRD42022366776.

Chinese herbal medicine Shufeng Jiedu capsule for mild to moderate COVID-19: a multicenter, randomized, double-blind, placebo-controlled phase II trial.

Background: The COVID-19 pandemic has had a profound global impact, although the majority of recently infected cases have presented with mild to moderate symptoms. Previous clinical studies have demonstrated that Shufeng Jiedu (SFJD) capsule, a Chinese herbal patent medicine, effectively alleviates symptoms associated with the common cold, H1N1 influenza, and COVID-19. This study aimed to assess the efficacy and safety of SFJD capsules in managing symptoms of mild to moderate COVID-19 infection. Methods: A randomized, double-blind, placebo-controlled trial was conducted from May to December 2022 at two hospitals in China. Mild and moderate COVID-19-infected patients presenting respiratory symptoms within 3 days from onset were randomly assigned to either the SFJD or placebo groups in a 1:1 ratio. Individuals received SFJD capsules or a placebo three times daily for five consecutive days. Participants were followed up for more than 14 days after their RT-PCR nucleoid acid test for SARS-CoV-2 turned negative. The primary outcome measure was time to alleviate COVID-19 symptoms from baseline until the end of follow-up. Results: A total of 478 participants were screened; ultimately, 407 completed the trial after randomization (SFJD, n = 203; placebo, n = 204). No statistically significant difference in baseline parameters was observed between the two groups. The median time to alleviate all symptoms was 7 days in the SFJD group compared to 8 days in the placebo group (p = 0.037). Notably, the SFJD group significantly attenuated fever/chills (p = 0.04) and headache (p = 0.016) compared to the placebo group. Furthermore, the median time taken to reach normal body temperature within 24 h was reduced by 7 hours in the SFJD group compared to the placebo group (p = 0.033). No deaths or instances of serious or critical conditions occurred during this trial period; moreover, no serious adverse events were reported. Conclusion: The trial was conducted in a unique controlled hospital setting, and the 5-day treatment with SFJD capsules resulted in a 1-day reduction in overall symptoms, particularly headache and fever/chills, among COVID-19-infected participants with mild or moderate symptoms. Compared to placebo, SFJD capsules were found to be safe with fewer side effects. SFJD capsules could potentially serve as an effective treatment for alleviating mild to moderate symptoms of COVID-19. Clinical Trial Registration: https://www.isrctn.com/, identifier ISRCTN14236594.

GDF-15 is a potential candidate biomarker for an elevated risk of cardiotoxicity in breast cancer patients receiving neoadjuvant dual anti-HER2 therapy.

Objective: Growth differentiation factor 15 (GDF-15) is a stress-responsive cytokine that regulates myocardial injury, cardiac overloading pressure, and inflammation and is related to the risk of cardiovascular diseases and events. The current study aimed to investigate the correlation of GDF-15 levels with clinical features, biochemical indices, and especially the risk of cardiotoxicity in breast cancer patients receiving neoadjuvant dual anti-HER2 therapy. Methods: A total of 103 HER2-positive breast cancer patients who underwent neoadjuvant dual anti-HER2 therapy (trastuzumab and pertuzumab plus chemotherapy) were included. Serum GDF-15 levels before neoadjuvant treatment were detected by enzyme-linked immunosorbent assay. Cardiotoxicity was evaluated during neoadjuvant therapy by referring to a decline of ≥10 percentage points in the left ventricular ejection fraction from baseline to an absolute level less than 50%. Results: GDF-15 exhibited a skewed distribution, with a median level of 714 (range: 207-1805) pg/mL. GDF-15 was positively correlated with age (p = 0.037), diabetes (p = 0.036), and the N-terminal pro-brain natriuretic peptide level (p = 0.013) and positively correlated with the total cholesterol level (p = 0.086) and troponin T level (p = 0.082), but these correlations were not statistically significant. A total of 6.8% of patients experienced cardiotoxicity during neoadjuvant therapy. By comparison, the GDF-15 level was greater in patients who experienced cardiotoxicity than in those who did not (p = 0.008). A subsequent receiver operating characteristic curve revealed that GDF-15 predicted cardiotoxicity risk, with an area under the curve of 0.803 (95% CI: 0.664-0.939). After multivariate adjustment, GDF-15 independently predicted a greater risk of cardiotoxicity (p = 0.020). Conclusion: GDF-15 is a candidate biomarker for increased risk of cardiotoxicity in breast cancer patients receiving neoadjuvant dual anti-HER2 therapy.

Effects of myo-inositol on regulating glucose and lipid metabolism and alternative splicing events coexpressed with lncRNAs in the liver tissues of diabetic mice.

Objective: Recent studies have shown that gene alternative splicing (AS) and long noncoding RNAs (lncRNAs) are involved in diabetes mellitus (DM) and its complications. Currently, myo-inositol (MI) is considered as effective for the treatment of insulin resistance and lipid metabolism disorders in diabetes patients. We hope to better explore the potential roles of gene AS and lncRNAs in liver glucose and lipid metabolism in diabetes, as well as the effects of myo-inositol treatment, through transcriptome analysis. Methods: This study analysed glucose and lipid metabolism-related biochemical indicators and liver HE staining in four groups of mice: the control group (Ctrl group), the diabetes group (DM group), the myo-inositol treatment group (MI group), and the metformin treatment group (Met group). The changes in relevant gene-regulated alternative splicing events (RASEs) and lncRNAs were analysed by RNA sequencing of liver tissue, and coexpression analysis and functional enrichment analysis were used to predict the possible lncRNAs and RASEs involved in liver glucose and lipid metabolism. Result: Metformin and myo-inositol alleviated insulin resistance, lipid metabolism disorders, and hepatic steatosis in diabetic mice. Transcriptome sequencing analysis revealed differential splicing events of genes related to lipid metabolism and differentially expressed lncRNAs (DElncRNAs). Six different lncRNAs and their potentially interacting splicing events were predicted. Conclusion: The present study revealed novel changes in RASEs and lncRNAs in the livers of diabetic mice following treatment with myo-inositol, which may shed light on the potential mechanisms by which myo-inositol delays and treats the progression of hepatic glucose and lipid metabolism in diabetes.

Open science practices in traditional, complementary, and integrative medicine research: A path to enhanced transparency and collaboration.

This educational article explores the convergence of open science practices and traditional, complementary, and integrative medicine (TCIM), shedding light on the potential benefits and challenges of open science for the development, dissemination, and implementation of evidence-based TCIM. We emphasize the transformative shift in medical science towards open and collaborative practices, highlighting the limited application of open science in TCIM research despite its growing acceptance among patients. We define open science practices and discuss those that are applicable to TCIM, including: study registration; reporting guidelines; data, code and material sharing; preprinting; publishing open access; and reproducibility/replication studies. We explore the benefits of open science in TCIM, spanning improved research quality, increased public trust, accelerated innovation, and enhanced evidence-based decision-making. We also acknowledge challenges such as data privacy concerns, limited resources, and resistance to cultural change. We propose strategies to overcome these challenges, including ethical guidelines, education programs, funding advocacy, interdisciplinary dialogue, and patient engagement. Looking to the future, we envision the maturation of open science in TCIM, the development of TCIM-specific guidelines for open science practices, advancements in data sharing platforms, the integration of open data and artificial intelligence in TCIM research, and changes in the context of policy and regulation. We foresee a future where open science in TCIM leads to a better evidence base, informed decision-making, interdisciplinary collaboration, and transformative impacts on healthcare and research methodologies, highlighting the promising synergy between open science and TCIM for holistic, evidence-based healthcare solutions.

Screening of aspiration pneumonia using the modified Mallampati classification tool in older adults.

Pneumonia is a major cause of morbidity and mortality in older adults. In the aging society, screening methods for predicting aspiration pneumonia are crucial for its prevention. Changes in the oropharyngeal morphology and hyoid bone position may increase the risk of aspiration pneumonia. This multicenter study aimed to investigate a simple and effective screening method for predicting dysphagia and aspiration pneumonia. Overall, 191 older adults (aged 65 years or older) were randomly sampled using the simple random sampling technique. Oropharyngeal morphology was assessed using the modified Mallampati classification, which reflects the size of the tongue in the oropharyngeal cavity. The hyoid position was measured as the distance between the menton and laryngeal prominence to evaluate aging-related changes in the muscles of the laryngopharynx. Dysphagia was assessed using the repetitive saliva swallowing test (RSST), which measures the number of swallowing movements in 30 seconds; dysphasia is defined as less than 3 swallowing movements in 30 seconds. The aspiration signs were assessed based on history of choking or coughing reflex during eating or drinking and medical history of pneumonia. The study findings revealed that the modified Mallampati classification was significantly correlated with a medical history of pneumonia. A higher incidence of pneumonia was evident in the lower Mallampati classification, which shows the smaller size of the tongue base in the oropharyngeal cavity. The results of this study suggest that the modified Mallampati classification may be a possible screening method to predict the occurrence of pneumonia.

MiR-146a alleviates inflammatory bowel disease in mice through systematic regulation of multiple genetic networks.

Introduction: Inflammatory bowel disease (IBD) is a chronic disease involving multiple genes, and the current available targeted drugs for IBD only deliver moderate efficacy. Whether there is a single gene that systematically regulates IBD is not yet known. MiR-146a plays a pivotal role in repression of innate immunity, but its function in the intestinal inflammation is sort of controversy, and the genetic regulatory networks regulated by miR-146a in IBD has not been revealed. Methods: RT-qPCR was employed to detect the expression of miR-146a in IBD patients and in a mouse IBD model induced by dextran sulfate sodium (DSS), and then we generated a miR-146a knock-out mouse line with C57/Bl6N background. The disease activity index was scored in DSS-treated miR-146a deficiency mice and their wild type (WT) littermates. Bulk RNA-sequencing, RT-qPCR and immunostaining were done to illustrate the downstream genetic regulatory networks of miR-146a in flamed colon. Finally, the modified miR-146a mimics were used to treat DSS-induced IBD in miR-146a knock-out and WT IBD mice. Results: We showed that the expression of miR-146a in the colon was elevated in dextran sulfate sodium (DSS)-induced IBD mice and patients with IBD. DSS induced dramatic body weight loss and more significant rectal bleeding, shorter colon length, and colitis in miR-146a knock-out mice than WT mice. The miR-146a mimics alleviated DSS-induced symptoms in both miR-146a-/- and WT mice. Further RNA sequencing illustrated that the deficiency of miR-146a de-repressed majority of DSS-induced IBD-related genes that cover multiple genetic regulatory networks in IBD, and supplementation with miR-146a mimics inhibited the expression of many IBD-related genes. Quantitative RT-PCR or immunostaining confirmed that Ccl3, Saa3, Csf3, Lcn2, Serpine1, Serpine2, MMP3, MMP8, MMP10, IL1A, IL1B, IL6, CXCL2, CXCL3, S100A8, S100A9, TRAF6, P65, p-P65, and IRAK1 were regulated by miR-146a in DSS induced IBD. Among them, MMP3, MMP10, IL6, IL1B, S100A8, S100A9, SERPINE1, CSF3, and IL1A were involved in the active stage of IBD in humans. Discussion: Our date demonstrated that miR-146a acts as a top regulator in C57/BL6N mice to systematically repress multiple genetic regulatory networks involved in immune response of intestine to environment factors, and combinatory treatment with miR-146a-5p and miR-146a-3p mimics attenuates DSS-induced IBD in mice through down-regulating multiple genetic regulatory networks which were increased in colon tissue from IBD patients. Our findings suggests that miR-146a is a top inhibitor of IBD, and that miR-146a-5p and miR-146a-3p mimics might be potential drug for IBD.

Dried fruit intake can lower the risk of ulcerative colitis: evidence from a Mendelian randomization study.

BACKGROUND AND OBJECTIVES: This study aims to examine the causal relationship between dietary factors and ulcerative colitis (UC). METHODS AND STUDY DESIGN: The analysis utilized data from genome-wide association studies (GWAS). Dried fruit, vegetables, processed meat, fresh fruit, and cereal intake were examined as exposure factors. UC was considered the outcome. Two-sample Mendelian randomization (TSMR) analysis was performed using methods. Heterogeneity and horizontal pleiotropy assessments were conducted to ensure the robustness of our findings. Additionally, we applied False Discovery Rate (FDR) corrections for multiple tests. RESULTS: The analysis revealed a significant inverse causal relationship between dried fruit intake and UC risk (odds ratio [OR]: 0.488, 95% confidence interval [CI]: 0.261 to 0.915, p = 0.025). No significant association was observed between vegetable intake (OR: 1.742, 95% CI: 0.561 to 5.415, p = 0.337), processed meat intake (OR: 1.136, 95% CI: 0.552 to 2.339, p = 0.729), fresh fruit intake (OR: 0.977, 95% CI: 0.465 to 2.054, p = 0.952), cereal intake (OR: 1.195, 95% CI: 0.669 to 2.134, p = 0.547). The low heterogeneity observed across analyses and the confirmation of stability through leave-one-out analysis reinforce the reliability of these results. Moreover, after adjusting for multiple tests, none of the dietary factors reached a p-value below the conventional significance threshold of 0.05. CONCLUSIONS: This study provides evidence of a potential association between dried fruit intake and a reduced risk of UC. Further MR studies incorporating larger GWAS datasets are needed to confirm these findings.

Publication Trends and Hot Spots of ChatGPT's Application in the Medicine.

This study aimed to analyze the current landscape of ChatGPT application in the medical field, assessing the current collaboration patterns and research topic hotspots to understand the impact and trends. By conducting a search in the Web of Science, we collected literature related to the applications of ChatGPT in medicine, covering the period from January 1, 2000 up to January 16, 2024. Bibliometric analyses were performed using CiteSpace (V6.2., Drexel University, PA, USA) and Microsoft Excel (Microsoft Corp.,WA, USA) to map the collaboration among countries/regions, the distribution of institutions and authors, and clustering of keywords. A total of 574 eligible articles were included, with 97.74% published in 2023. These articles span various disciplines, particularly in Health Care Sciences Services, with extensive international collaboration involving 73 countries. In terms of countries/regions studied, USA, India, and China led in the number of publications. USA ot only published nearly half of the total number of papers but also exhibits a highest collaborative capability. Regarding the co-occurrence of institutions and scholars, the National University of Singapore and Harvard University held significant influence in the cooperation network, with the top three authors in terms of publications being Wiwanitkit V (10 articles), Seth I (9 articles), Klang E (7 articles), and Kleebayoon A (7 articles). Through keyword clustering, the study identified 9 research theme clusters, among which "digital health"was not only the largest in scale but also had the most citations. The study highlights ChatGPT's cross-disciplinary nature and collaborative research in medicine, showcasing its growth potential, particularly in digital health and clinical decision support. Future exploration should examine the socio-economic and cultural impacts of this trend, along with ChatGPT's specific technical uses in medical practice.

Modified Lichong decoction intervenes in colorectal cancer by modulating the intestinal flora and the Wnt/ß-catenin signaling pathway.

BACKGROUND: The pathogenesis and treatment of colorectal cancer (CRC) continue to be areas of ongoing research, especially the benefits of traditional Chinese medicine (TCM) in slowing the progression of CRC. This study was conducted to investigate the effectiveness and mechanism of action of modified Lichong decoction (MLCD) in inhibiting CRC progression. METHODS: We established CRC animal models using azoxymethane/dextran sodium sulfate (AOM/DSS) and administered high, medium, or low doses of MLCD or mesalazine (MS) for 9 weeks to observe MLCD alleviation of CRC. The optimal MLCD dose group was then subjected to metagenomic and RNA sequencing (RNA-seq) to explore the differentially abundant flora and genes in the control, model and MLCD groups. Finally, the mechanism of action was verified using WB, qRT‒PCR, immunohistochemistry and TUNEL staining. RESULTS: MLCD inhibited the progression of CRC, and the optimal effect was observed at high doses. MLCD regulated the structure and function of the intestinal flora by decreasing the abundance of harmful bacteria and increasing that of beneficial bacteria. The differentially expressed genes were mainly associated with the Wnt/ß-catenin pathway and the cell cycle. Molecular biology analysis indicated that MLCD suppressed the Wnt/ß-catenin pathway and the epithelial-mesenchymal transition (EMT), inhibited abnormal cell proliferation and promoted intestinal epithelial cell apoptosis. CONCLUSION: MLCD mitigated the abnormal growth of intestinal epithelial cells and promoted apoptosis, thereby inhibiting the progression of CRC. This inhibition was accomplished by modifying the intestinal microbiota and disrupting the Wnt/ß-catenin pathway and the EMT. Therefore, MLCD could serve as a potential component of TCM prescriptions for CRC treatment.

Atom-Modified gDNA Enhances Cleavage Activity of TtAgo Enabling Ultra-Sensitive Nucleic Acid Testing.

The DNA-guided (gDNA) Argonaute from Thermus thermophilus (TtAgo) has little potential for nucleic acid detection and gene editing due to its poor dsDNA cleavage activity at relatively low temperature. Herein, the dsDNA cleavage activity of TtAgo is enhanced by using 2'-fluorine (2'F)-modified gDNA and developes a novel nucleic acid testing strategy. This study finds that the gDNA with 2'F-nucleotides at the 3'-end (2'F-gDNA) can promote the assembly of the TtAgo-guide-target ternary complex significantly by increasing its intermolecular force to target DNA and TtAgo, thereby providing ≈40-fold activity enhancement and decreasing minimum reaction temperature from 65 to 60 °C. Based on this outstanding advance, a novel nucleic acid testing strategy is proposed, termed FAST, which is performed by using the 2'F-gDNA/TtAgo for target recognition and combining it with Bst DNA polymerase for nucleic acid amplification. By integrating G-quadruplex and Thioflavin T, the FAST assay achieves one-pot real-time fluorescence analysis with ultra-sensitivity, providing a limit of detection up to 5 copies (20 µL reaction mixture) for miR-21 detection. In summary, an atom-modification-based strategy has been developed for enhancing the cleavage activity of TtAgo efficiently, thereby improving its practicability and establishing a TtAgo-based nucleic acid testing technology with ultra-sensitivity and high-specificity.

A case study of a liver transplant-treated patient with glycogen storage disease type Ia presenting with multiple inflammatory hepatic adenomas: an analysis of clinicopathologic and genetic data.

BACKGROUND: Glycogen storage disease (GSD) is a disease caused by excessive deposition of glycogen in tissues due to genetic disorders in glycogen metabolism. Glycogen storage disease type I (GSD-I) is also known as VonGeirk disease and glucose-6-phosphatase deficiency. This disease is inherited in an autosomal recessive manner, and both sexes can be affected. The main symptoms include hypoglycaemia, hepatomegaly, acidosis, hyperlipidaemia, hyperuricaemia, hyperlactataemia, coagulopathy and developmental delay. CASE PRESENTATION: Here, we present the case of a 13-year-old female patient with GSD Ia complicated with multiple inflammatory hepatic adenomas. She presented to the hospital with hepatomegaly, hypoglycaemia, and epistaxis. By clinical manifestations and imaging and laboratory examinations, we suspected that the patient suffered from GSD I. Finally, the diagnosis was confirmed by liver pathology and whole-exome sequencing (WES). WES revealed a synonymous mutation, c.648 G > T (p.L216 = , NM_000151.4), in exon 5 and a frameshift mutation, c.262delG (p.Val88Phefs*14, NM_000151.4), in exon 2 of the G6PC gene. According to the pedigree analysis results of first-generation sequencing, heterozygous mutations of c.648 G > T and c.262delG were obtained from the patient's father and mother. Liver pathology revealed that the solid nodules were hepatocellular hyperplastic lesions, and immunohistochemical (IHC) results revealed positive expression of CD34 (incomplete vascularization), liver fatty acid binding protein (L-FABP) and C-reactive protein (CRP) in nodule hepatocytes and negative expression of ß-catenin and glutamine synthetase (GS). These findings suggest multiple inflammatory hepatocellular adenomas. PAS-stained peripheral hepatocytes that were mostly digested by PAS-D were strongly positive. This patient was finally diagnosed with GSD-Ia complicated with multiple inflammatory hepatic adenomas, briefly treated with nutritional therapy after diagnosis and then underwent living-donor liver allotransplantation. After 14 months of follow-up, the patient recovered well, liver function and blood glucose levels remained normal, and no complications occurred. CONCLUSION: The patient was diagnosed with GSD-Ia combined with multiple inflammatory hepatic adenomas and received liver transplant treatment. For childhood patients who present with hepatomegaly, growth retardation, and laboratory test abnormalities, including hypoglycaemia, hyperuricaemia, and hyperlipidaemia, a diagnosis of GSD should be considered. Gene sequencing and liver pathology play important roles in the diagnosis and typing of GSD.

Effects of Miscut on Step Instabilities in Homo-Epitaxially Grown GaN.

The rough morphology at the growth surface results in the non-uniform distribution of indium composition, intentionally or unintentionally doped impurity, and thus impacts the performance of GaN-based optoelectronic and vertical power electronic devices. We observed the morphologies of unintentionally doped GaN homo-epitaxially grown via MOCVD and identified the relations between rough surfaces and the miscut angle and direction of the substrate. The growth kinetics under the effect of the Ehrlich-Schwoebel barrier were studied, and it was found that asymmetric step motions in samples with a large miscut angle or those grown at high temperature were the causes of step-bunching. Meandering steps were believed to be caused by surface free energy minimization for steps with wide terraces or deviating from the [11¯00] m-direction.

Ophiocordyceps sinensis preparations combined with the renin-angiotensin system inhibitor for diabetic kidney disease treatment: an umbrella review of systematic reviews and network meta-analysis.

Aims: This study aimed to synthesize the evidence of the comparative effectiveness and safety of Ophiocordyceps sinensis (OS) preparations combined with renin-angiotensin system inhibitors (RASi) for diabetic kidney disease (DKD). Methods: Eight databases were searched from their inception to May 2023. Systematic reviews (SRs) of OS preparations combined with RASi for DKD were identified. Randomized controlled trials (RCTs) from the included SRs and additional searching were performed for data pooling. Cochrane risk-of-bias 2 (RoB 2) tool and AMSTAR 2 were used to evaluate the methodological quality of RCTs and SRs, respectively. A Bayesian network meta-analysis was performed to compare the add-on effect and safety of OS preparations for DKD. The certainty of evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: Fourteen SRs were included, whose methodological quality was assessed as high (1/14) or critically low (13/14). After combining additional searching, 157 RCTs were included, involving 13,143 participants. The quality of the RCTs showed some concerns (155/157) or high risk (2/157). Jinshuibao capsules and tablets, Bailing capsules and tablets, and Zhiling capsules were evaluated. Compared to RASi, adding either of the OS capsular preparations resulted in a decreased 24-h urinary total protein levels. OS preparations ranked differently in each outcome. Jinshuibao capsules plus RASi were beneficial in reducing urinary protein, serum creatinine, serum urea nitrogen, and blood glucose levels, with moderate-certainty evidence. No serious adverse events were observed after adding OS to RASi. Conclusion: Combining OS capsular preparations with RASi appeared to be associated with decreased urinary total protein levels in DKD patients. Further high-quality studies are needed to confirm. Systematic Review Registration: INPASY202350066.

The efficiency of stem cell differentiation into functional beta cells for treating insulin-requiring diabetes: Recent advances and current challenges.

In recent years, the potential of stem cells (SCs) to differentiate into various types of cells, including ß-cells, has led to a significant boost in development. The efficiency of this differentiation process and the functionality of the cells post-transplantation are crucial factors for the success of stem cell therapy in diabetes. Herein, this article reviews the current advances and challenges faced by stem cell differentiation into functional ß-cells for diabetes treatment. In vitro, researchers have sought to enhance the differentiation efficiency of functional ß-cells by mimicking the normal pancreatic development process, using gene manipulation, pharmacological and culture conditions stimulation, three-dimensional (3D) and organoid culture, or sorting for functional ß-cells based on mature islet cell markers. Furthermore, in vivo studies have also looked at suitable transplantation sites, the enhancement of the transplantation microenvironment, immune modulation, and vascular function reconstruction to improve the survival rate of functional ß-cells, thereby enhancing the treatment of diabetes. Despite these advancements, developing stem cells to produce functional ß-cells for efficacious diabetes treatment is a continuous research endeavor requiring significant multidisciplinary collaboration, for the stem-cell-derived beta cells to evolve into an effective cellular therapy.