Structural and Functional Differences in Small Intestinal and Fecal Microbiota: 16S rRNA Gene Investigation in Rats.

To compare the differences in floral composition and functions between the two types of microbiota, ileal contents and feces were collected from Sprague Dawley (SD) rats fed in a conventional or specific-pathogen free (SPF) environment and rats fed a high-fat diet (HFD), and the V3-V4 region of the 16S ribosomal ribonucleic acid (rRNA) gene in these rats was then amplified and sequenced. Compared with feces, about 60% of the bacterial genera in the ileum were exclusive, with low abundance (operational taxonomic units (OTUs) < 1000). Of bacteria shared between the ileum and feces, a few genera were highly abundant (dominant), whereas most had low abundance (less dominant). The dominant bacteria differed between the ileum and feces. Ileal bacteria showed greater ß-diversity, and the distance between in-group samples was nearer than that between paired ileum-feces samples. Moreover, the ileum shared various biomarkers and functions with feces (p < 0.05). The HFD and SPF conditions had a profound influence on α-diversity and abundance but not on the exclusive/shared features or ß-diversity of samples. The present findings suggested that, under conventional circumstances, fecal bacteria can represent approximately 40% of the low abundant ileal bacterial genera and that dominant fecal bacteria failed to represent the ileal dominant flora. Moreover, fecal flora diversity does not reflect ß-diversity in the ileum.

Novel Sustained Release Azithromycin Resinate Fabricated by One-Pot Ion-exchange Performed in Hydro-alcoholic Solution.

Drug-resin complexes usually form in the aqueous phase. For poorly water-soluble drugs, low drug loading limits the use of resin in drug formulation. In this study, we used a new method to prepare azithromycin resinates, improving the drug loading rate, shortening the preparation time and simplifying the process. We used hydro-alcoholic solution as the drug loading solvent and the ion exchange resin as the carrier, and this method enabled the resin to adsorb both the retardant and the drug. The sustained release effect of retardant Eudragit RL, RS100 was analyzed. Drug loading efficiency, release profiles, morphology, physicochemical characterization and pharmacokinetic study were assessed. Preparation of drug resinate by batch method resulted in 14% higher drug loading of azithromycin and 3.5 h shorter loading time as compared to pure water for hydroalcoholic solution as drug loading solvent. Raman mappings demonstrated that the retardant with higher molecular weight was more likely to adsorb to the outer layer of the resin compared to the drug. The in vitro release and in vivo pharmacokinetic study of azithromycin resinates showed a sustained release profile with few gastrointestinal adverse effects. Therefore, the addition of ethanol not only improved the efficiency of drug loading but also showed sustained-release effect with one-pot preparation of azithromycin resinates.

[Research progress in coatings with active compounds and extracts of traditional Chinese medicines for coronary intervention devices].

In recent years, the incidence and mortality rates of cardiovascular diseases in China have kept rising, with no significant reduction in disease burden observed. Percutaneous coronary intervention(PCI) is an effective approach for treating coronary artery disease. Drug-eluting stents and drug-coated balloons are currently the most common PCI devices used in clinical practice. However, challenges with restenosis and late-stage thrombotic events persist. Inhibiting the proliferation of vascular smooth muscle cells while enhancing endothelial cell activity is crucial for reducing restenosis and preventing thrombosis, and it remains a challenge in research. The active compounds and extracts of traditional Chinese medicine(TCM), particularly the combinations of active compounds in coatings, possess multi-target potential and serve as a supplement to coatings prepared from synthetic compounds. This review elucidates the application of TCM active compounds(such as arsenic trioxide, paclitaxel, hirudin, tetramethylpyrazine, emodin, oxymatrine, and curcumin), combinations of TCM active compounds(paclitaxel/hirudin, geniposide/baicalin), and TCM extracts(such as Curcumae Rhizoma extract and Tripterygium hypoglaucum extract) in the coatings for PCI devices in recent years. Furthermore, this review expounds the current challenges and future prospects in this field, giving insights into the innovation of PCI devices.

Lone-Star retractor perineal exposure method for laparoscopic abdominal perineal resection of rectal cancer.

BACKGROUND: The abdominal perineal resection (APR), historically referred to as Mile's procedure, stands as a time-honored surgical intervention for rectal cancer management. Advancements in surgical techniques and the advent of neoadjuvant therapies have significantly improved the rate of sphincter preservation among patients afflicted with rectal cancer, including those with ultralow rectal cancer. Despite these improvements, APR maintains its irreplaceable role in the clinical landscape, particularly for cases involving low rectal cancer with encroachment on the external anal sphincter or levator ani muscles. Optimal perineal exposure stands as a pivotal phase in APR, given that the precision of this maneuver is directly correlated with both the safety of the surgery and the patient's subsequent long-term prognosis. AIM: To evaluate the value of Lone-Star retractor (LSR) perineal exposure method in the treatment for laparoscopic APR of rectal cancer. METHODS: We reviewed the records of 38 patients with rectal cancer at Anqing Municipal Hospital from January 2020 to December 2023, including 20 patients who underwent the APR procedure with a LSR perineal exposure method (LSR group) and 18 patients who underwent the APR procedure with a conventional perineal exposure method (control group). In the LSR group, following incision of the skin and subcutaneous tissue, the LSR was placed and dynamically adjusted according to the surgical plane to fully expose the perineal operative field. RESULTS: A total of 38 patients underwent laparoscopic APR, none of whom were found to have distant metastasis upon intraoperative exploration. Perineal blood loss, the postoperative hospital stays and the wound pain scores in the LSR group were significantly lower than those in the control group. A single surgeon completed the perineal operation significantly more often in the LSR group than in the control group (P < 0.05). The incidence of infection via the perineal incision in the LSR group was significantly lower than that in the control group (P < 0.05). No cases of distant metastasis or local recurrence were found among the patients at the postoperative follow-up. CONCLUSION: The application of the LSR technique might be helpful for performing perineal exposure during APR for rectal cancer and could reduce the incidence of perineal complications, shorten the postoperative hospital stay, improve postoperative pain, and allow one surgeon to perform the perineal operation.

Traumatic cervical tracheal trunk complete rupture combined with cardiac arrest: A case report.

Traumatic main bronchus rupture is a relatively rare injury in thoracic trauma, which is extremely critical, with a mortality rate as high as 70% - 80%. The complete rupture and displacement of the traumatic cervical trachea can lead to asphyxia, hypoxia, and cardiac arrest, even death of the patient in a short time. We performed emergency surgery with the support of extracorporeal membrane oxygenation for a case of traumatic cervical tracheal trunk complete rupture and displacement combined with cardiac arrest and achieved a successful rescue. We summarized our experience and found that timely surgical reconstruction of the airway is the key to increasing the traumatic main bronchus rupture survival of patients.

Clinical manifestations and viral kinetics of people with Mpox: A case series during the 2023 outbreak in Taiwan.

Monkeypox (Mpox) has emerged as a global threat since 2022. We reported 14 cases of Mpox in 10 people with HIV (PWH) and 4 people without HIV (PWoH), of whom 64.3% had sexually transmitted co-infections. Severe complications of Mpox and prolonged viral shedding might occur in both PWH and PWoH.

RNA reading protein YTHDF2 mediates Benzo(k)fluoranthene induced male reproductive injury by regulating the stability of BCL2.

Benzo (k) fluoranthene (BkF) has adverse effects on male reproduction, but its specific mechanism of action is still unclear. This study focused on the role of RNA reading protein YTHDF2 and its mechanism in BkF induced male reproductive injury. Mouse GC-2 spermatocytes were exposed to 0, 40, 80, 160 µM BkF. It was found that BkF significantly increased the apoptosis of GC-2 cell and decreased its survival rate. BCL2 in spermatocytes decreased significantly, while the expression of P53 and BAX exhibited a notable increase. Interestingly, the expression of RNA reading protein YTHDF2 progressively rose in tandem with the escalating BkF exposure dosage. Overexpression of YTHDF2 significantly reduced the viability of cells and increased the apoptosis rate. Meanwhile, there was a substantial increase in the expression of P53 and BAX, BCL2 was significantly down-regulated. On the contrary, interfering with YTHDF2 increased cell proliferation and reduced cell apoptosis. Furthermore, YTHDF2 overexpression exacerbated the decrease in cell viability under BkF exposure, while YTHDF2 knockdown was the opposite. The results from the RIP assay demonstrated a significant enhancement in the interaction of YTHDF2 protein with BCL2 mRNA following the overexpression of YTHDF2. In addition, animal experiments showed that there was an increase in apoptosis and a decrease in proliferation of testicular cells in mice in the high-dose (30 mg/kg) BkF group by TUNEL staining and Ki67 staining. Immunohistochemical analysis showed that BCL2 levels were significantly lower in the high-dose group than in the control group, while YTHDF2, P53 and BAX were dramatically increased. In summary, our study suggests that YTHDF2 has been implicated in BkF-induced male reproductive injury by promoting the degradation of BCL2.

Clinical characteristics of sudden hearing loss during pregnancy.

Objective: The objective of this study was to explore the clinical characteristics and management of sudden hearing loss (HL) during pregnancy, thus better guiding the clinical practice. Methods: The clinical and follow-up data of 17 patients (17 ears) with sudden HL during pregnancy were analyzed retrospectively (the observe group). Twelve nonpregnant female patients (12 ears) with sudden HL of similar clinical characteristics were selected as the control group. The prognosis of the two groups was compared. All the patients were followed up after delivery, and two of them were readmitted to the hospital 1-2 months after delivery. Results: The observe group had better improvement in hearing and a higher response rate compared to the control group. The pure tone hearing and speech recognition rate of patients could still be improved after the readmitted treatment, and the hearing could partially recover spontaneously during follow-up. The laboratory indicators that affect the inflammatory response and coagulation pathway were significantly different between the two groups. Conclusions: The hearing condition of sudden HL during pregnancy is severe, and the prognosis of these patients is better than nonpregnant patients of similar clinical characteristics. Postpartum treatment is still effective, and some patients showed self-healing with time during follow-up. The inflammatory response and coagulation function may affect the hearing of patients through a metabolic pathway.

Elevated temperature as the dominant stressor on the harmful algal bloom-causing dinoflagellate Prorocentrum obtusidens in a future ocean scenario.

Marine dinoflagellates are increasingly affected by ongoing global climate changes. While understanding of their physiological and molecular responses to individual stressors anticipated in the future ocean has improved, their responses to multiple concurrent stressors remain poorly understood. Here, we investigated the individual and combined effects of elevated temperature (26 °C relative to 22 °C), increased pCO2 (1000 µatm relative to 400 µatm), and high nitrogen: phosphorus ratio (180:1 relative to 40:1) on a harmful algal bloom-causing dinoflagellate Prorocentrum obtusidens under short-term (28 days) exposure. Elevated temperature was the most dominant stressor affecting P. obtusidens at physiological and transcriptomic levels. It significantly increased cell growth rate and maximum photosynthetic efficiency (Fv/Fm), but reduced chlorophyll a, particulate organic carbon, particulate organic nitrogen, and particulate organic phosphorus. Elevated temperature also interacted with other stressors to produce synergistic positive effects on cell growth and Fv/Fm. Transcriptomic analysis indicated that elevated temperature promoted energy production by enhancing glycolysis, tricarboxylic acid cycle, and nitrogen and carbon assimilation, which supported rapid cell growth but reduced material storage. Increased pCO2 enhanced the expression of genes involved in ionic acid-base regulation and oxidative stress resistance, whereas a high N:P ratio inhibited photosynthesis, compromising cell viability, although the effect was alleviated by elevated temperature. The combined effect of these multiple stressors resulted in increased energy metabolism and up-regulation of material-synthesis pathways compared to the effect caused by elevated temperature alone. Our results underscore ocean warming as the predominant stressor for dinoflagellates and highlight the complex, synergistic effects of multi-stressors on dinoflagellates.

Artificial Meshed Vessel-Induced Dimensional Breaking Growth of Human Brain Organoids and Multiregional Assembloids.

Brain organoids are widely used to model brain development and diseases. However, a major challenge in their application is the insufficient supply of oxygen and nutrients to the core region, restricting the size and maturation of the organoids. In order to vascularize brain organoids and enhance the nutritional supply to their core areas, two-photon polymerization (TPP) 3D printing is employed to fabricate high-resolution meshed vessels in this study. These vessels made of photoresist with densely distributed micropores with a diameter of 20 µm on the sidewall, are cocultured with brain organoids to facilitate the diffusion of culture medium into the organoids. The vascularized organoids exhibit dimensional breaking growth and enhanced proliferation, reduced hypoxia and apoptosis, suggesting that the 3D-printed meshed vessels partially mimic vascular function to promote the culture of organoids. Furthermore, cortical, striatal and medial ganglionic eminence (MGE) organoids are respectively differentiated to generate Cortico-Striatal-MGE assembloids by 3D-printed vessels. The enhanced migration, projection and excitatory signaling transduction are observed between different brain regional organoids in the assembloids. This study presents an approach using TPP 3D printing to construct vascularized brain organoids and assembloids for enhancing the development and assembly, offering a research model and platform for neurological diseases.

Worldwide burden of liver cancer due to metabolic dysfunction-associated steatohepatitis from 1990 to 2019: insights from the Global Burden of Disease study.

Introduction: Metabolic dysfunction-associated steatohepatitis (MASH) is increasingly becoming a prevalent cause of hepatocellular carcinoma (HCC). Our study examines the burden of MASH-related HCC globally, regionally, and nationally, along with associated risk factors from 1990 to 2019, considering variables such as age, sex, and socioeconomic status. Objective: We aimed to report the global, regional, and national burden of liver cancer due to MASH and its attributable risk factors between 1990 and 2019, by age, sex, and sociodemographic index (SDI). Methods: Utilizing the Global Burden of Disease 2019 project, we analyzed data on prevalence, mortality, and disability-adjusted life years (DALYs) for liver cancer attributable to MASH across 204 countries. We provided counts and rates per 100,000 population, including 95% uncertainty intervals. Results: In 2019, there were 46.8 thousand cases of MASH-related HCC, leading to 34.7 thousand deaths, and 795.8 thousand DALYs globally. While the prevalence increased by 19.8% since 1990, the death and DALY rates decreased by 5.3% and 15.1%, respectively. The highest prevalence was in High-income Asia Pacific, with the greatest increases observed in Australasia, Central Asia, and High-income North America. Southern Sub-Saharan Africa reported the highest death rate, while the lowest rates were in parts of Latin America, Central Sub-Saharan Africa, and Eastern Europe. DALY rates were the highest in Southern Sub-Saharan Africa and the lowest in Tropical Latin America. Discussion: The burden of MASH-related HCC is expected to rise slightly over the next decade. This disease, which is not associated with the SDI, remains a major public health problem. In addition, the escalating rates of obesity, demographic shifts, and an aging population could position MASH as a leading factor in liver cancer cases, surpassing viral hepatitis. It is imperative, therefore, that the forthcoming years see the implementation of strategic interventions aimed at the early detection and prevention of liver cancer associated with MASH.

STUB1-mediated K63-linked ubiquitination of UHRF1 promotes the progression of cholangiocarcinoma by maintaining DNA hypermethylation of PLA2G2A.

BACKGROUND: Cholangiocarcinoma (CCA) is a highly malignant tumor characterized by a lack of effective targeted therapeutic strategies. The protein UHRF1 plays a pivotal role in the preservation of DNA methylation and works synergistically with DNMT1. Posttranscriptional modifications (PTMs), such as ubiquitination, play indispensable roles in facilitating this process. Nevertheless, the specific PTMs that regulate UHRF1 in CCA remain unidentified. METHODS: We confirmed the interaction between STUB1 and UHRF1 through mass spectrometry analysis. Furthermore, we investigated the underlying mechanisms of the STUB1-UHRF1/DNMT1 axis via co-IP experiments, denaturing IP ubiquitination experiments, nuclear‒cytoplasmic separation and immunofluorescence experiments. The downstream PLA2G2A gene, regulated by the STUB1-UHRF1/DNMT1 axis, was identified via RNA-seq.  The negative regulatory mechanism of PLA2G2A was explored via bisulfite sequencing PCR (BSP) experiments to assess changes in promoter methylation. The roles of PLA2G2A and STUB1 in the proliferation, invasion, and migration of CCA cells were assessed using the CCK-8 assay, colony formation assay, Transwell assay, wound healing assay and xenograft mouse model. We evaluated the effects of STUB1/UHRF1 on cholangiocarcinoma by utilizing a primary CCA mouse model. RESULTS: This study revealed that STUB1 interacts with UHRF1, resulting in an increase in the K63-linked ubiquitination of UHRF1. Consequently, this facilitates the nuclear translocation of UHRF1 and enhances its binding affinity with DNMT1. The STUB1-UHRF1/DNMT1 axis led to increased DNA methylation of the PLA2G2A promoter, subsequently repressing its expression. Increased STUB1 expression in CCA was inversely correlated with tumor progression and overall survival. Conversely, PLA2G2A functions as a tumor suppressor in CCA by inhibiting cell proliferation, invasion and migration. CONCLUSIONS: These findings suggest that the STUB1-mediated ubiquitination of UHRF1 plays a pivotal role in tumor progression by epigenetically silencing PLA2G2A, underscoring the potential of STUB1 as both a prognostic biomarker and therapeutic target for CCA.

Novel Role of Endothelial CD45 in Regulating Endothelial-to-Mesenchymal Transition in Atherosclerosis.

Background: Protein-tyrosine-phosphatase CD45 is exclusively expressed in all nucleated cells of the hematopoietic system but is rarely expressed in endothelial cells. Interestingly, our recent study indicated that activation of the endogenous CD45 promoter in human endothelial colony forming cells (ECFCs) induced expression of multiple EndoMT marker genes. However, the detailed molecular mechanisms underlying CD45 that drive EndoMT and the therapeutic potential of manipulation of CD45 expression in atherosclerosis are entirely unknown. Method: We generated a tamoxifen-inducible EC-specific CD45 deficient mouse strain (EC-iCD45KO) in an ApoE-deficient (ApoE-/-) background and fed with a Western diet (C57BL/6) for atherosclerosis and molecular analyses. We isolated and enriched mouse aortic endothelial cells with CD31 beads to perform single-cell RNA sequencing. Biomedical, cellular, and molecular approaches were utilized to investigate the role of endothelial CD45-specific deletion in the prevention of EndoMT in ApoE-/- model of atherosclerosis. Results: Single-cell RNA sequencing revealed that loss of endothelial CD45 inhibits EndoMT marker expression and transforming growth factor-ß signaling in atherosclerotic mice. which is associated with the reductions of lesions in the ApoE-/- mouse model. Mechanistically, the loss of endothelial cell CD45 results in increased KLF2 expression, which inhibits transforming growth factor-ß signaling and EndoMT. Consistently, endothelial CD45 deficient mice showed reduced lesion development, plaque macrophages, and expression of cell adhesion molecules when compared to ApoE-/- controls. Conclusions: These findings demonstrate that the loss of endothelial CD45 protects against EndoMT-driven atherosclerosis, promoting KLF2 expression while inhibiting TGFß signaling and EndoMT markers. Thus, targeting endothelial CD45 may be a novel therapeutic strategy for EndoMT and atherosclerosis.

Microfluidic-blow-spinning of carvacrol-loaded porphyrin metal - organic framework nanofiber films with synergistic antibacterial capabilities for food packaging.

The adherence of foodborne microorganisms threatens human health, necessitating the development of antibacterial food packaging films. In this study, the antibacterial agent carvacrol (CV), hindered by its high volatility and intense aromatic odor, was encapsulated within the photosensitive metal-organic frameworks (MOFs) material PCN-224 (loading rate 50%). Subsequently, the microfluidic-blow-spinning (MBS) technique was employed for the rapid fabrication of CV@PCN-224/polycaprolactone (PCL)/chitosan (CS) nanofiber films. The incorporation of CV@PCN-224 NPs enhances the nanofiber films' thermal stability and mechanical properties and improves the water vapor permeability while maintaining the sustained release of CV over an extended period and good biocompatibility. Due to the simultaneous loading of antibacterial agent (CV) and photosensitive agent (PCN-224), the CV@PCN-224/PCL/CS films exhibited good synergistic antibacterial functionality, as demonstrated by effective inhibition against both E. coli and S. aureus. All results show the vast potential of the prepared nanofiber films in antibacterial food packaging.

Integrated metabolomics and transcriptomics analysis reveals the mechanism of Tangbi capsule for diabetic lower extremities arterial disease.

Objective: Tangbi capsule (TBC) is a traditional Chinese medicine prescription, which has the potential to improve the vascular insufficiency of lower extremities and limb numbness in diabetes. However, the potential mechanism remains unknown. This study aims to investigate the pharmacological effects and mechanism of TBC on rats with diabetic lower extremities arterial disease (LEAD). Methods: The mechanism of TBC on diabetic LEAD was investigated through metabolomics and transcriptomics analysis, and the main components of TBC were determined by mass spectrometry. The efficacy and mechanism of TBC on diabetic LEAD rats were investigated through in vitro experiments, histopathology, blood flow monitoring, western blot, and real-time polymerase chain reaction. Results: Mass spectrometry analysis identified 31 active chemical components in TBC including (2R)-2,3-Dihydroxypropanoic acid, catechin, citric acid, miquelianin, carminic acid, salicylic acid, formononetin, etc. In vitro analysis showed that TBC could reduce endothelial cell apoptosis and promote angiogenesis. Histopathological analysis showed that TBC led to an obvious improvement in diabetic LEAD as it improved fibrous tissue proliferation and reduced arterial wall thickening. In addition, TBC could significantly increase the expression levels of HIF-1α, eNOS, and VEGFA proteins and genes while reducing that of calpain-1 and TGF-ß, suggesting that TBC can repair vascular injury. Compared with the model group, there were 47 differentially expressed genes in the whole blood of TBC groups, with 25 genes upregulated and 22 downregulated. Eighty-seven altered metabolites were identified from the serum samples. Combining the changes in differentially expressed genes and metabolites, we found that TBC could regulate arginine biosynthesis, phenylalanine metabolism, pyrimidine metabolism, arachidonic acid metabolism, pyrimidine metabolism, arachidonic acid metabolism, nucleotide metabolism, vitamin B6 metabolism and other metabolic pathways related to angiogenesis, immune-inflammatory response, and cell growth to improve diabetic LEAD. Conclusion: TBC improved vascular endothelial injury, apoptosis, lipid accumulation, liver and kidney function, and restored blood flow in the lower extremities of diabetic LEAD rats. The mechanism of TBC in the treatment of diabetic LEAD may be related to the modulation of inflammatory immunity, lipid metabolism, and amino acid metabolism. This study presented preliminary evidence to guide the use of TBC as a therapy option for diabetic LEAD.

Discovery of Benzothiazol-2-ylthiophenylpyrazole-4-carboxamides as Novel Succinate Dehydrogenase Inhibitors.

Succinate dehydrogenase (SDH) has been considered an ideal target for discovering fungicides. To develop novel SDH inhibitors, in this work, 31 novel benzothiazol-2-ylthiophenylpyrazole-4-carboxamides were designed and synthesized using active fragment exchange and a link approach as promising SDH inhibitors. The findings from the tests on antifungal activity indicated that most of the synthesized compounds displayed remarkable inhibition against the fungi tested. Compound Ig N-(2-(((5-chlorobenzo[d]thiazol-2-yl)thio)methyl)phenyl)-3-(difluoromethyl)-1-methyl-1H-yrazole-4-carboxamide, with EC50 values against four kinds of fungi tested below 10 µg/mL and against Cercospora arachidicola even below 2 µg/mL, showed superior antifungal activity than that of commercial fungicide thifluzamide, and specifically compounds Ig and Im were found to show preventative potency of 90.6% and 81.3% against Rhizoctonia solani Kühn, respectively, similar to the positive fungicide thifluzamide. The molecular simulation studies suggested that hydrophobic interactions were the main driving forces between ligands and SDH. Encouragingly, we found that compound Ig can effectively promote the wheat seedlings and the growth of Arabidopsis thaliana. Our further studies indicated that compound Ig could stimulate nitrate reductase activity in planta and increase the biomass of plants.

Adapting cytoskeleton-mitochondria patterning with myocyte differentiation by promyogenic PRR33.

Coordinated cytoskeleton-mitochondria organization during myogenesis is crucial for muscle development and function. Our understanding of the underlying regulatory mechanisms remains inadequate. Here, we identified a novel muscle-enriched protein, PRR33, which is upregulated during myogenesis and acts as a promyogenic factor. Depletion of Prr33 in C2C12 represses myoblast differentiation. Genetic deletion of Prr33 in mice reduces myofiber size and decreases muscle strength. The Prr33 mutant mice also exhibit impaired myogenesis and defects in muscle regeneration in response to injury. Interactome and transcriptome analyses reveal that PRR33 regulates cytoskeleton and mitochondrial function. Remarkably, PRR33 interacts with DESMIN, a key regulator of cytoskeleton-mitochondria organization in muscle cells. Abrogation of PRR33 in myocytes substantially abolishes the interaction of DESMIN filaments with mitochondria, leading to abnormal intracellular accumulation of DESMIN and mitochondrial disorganization/dysfunction in myofibers. Together, our findings demonstrate that PRR33 and DESMIN constitute an important regulatory module coordinating mitochondrial organization with muscle differentiation.

Research progress on interferon and cellular senescence.

Since the 12 major signs of aging were revealed in 2023, people's interpretation of aging will go further, which is of great significance for understanding the occurrence, development, and intervention in the aging process. As one of the 12 major signs of aging, cellular senescence refers to the process in which the proliferation and differentiation ability of cells decrease under stress stimulation or over time, often manifested as changes in cell morphology, cell cycle arrest, and decreased metabolic function. Interferon (IFN), as a secreted ligand for specific cell surface receptors, can trigger the transcription of interferon-stimulated genes (ISGs) and play an important role in cellular senescence. In addition, IFN serves as an important component of SASP, and the activation of the IFN signaling pathway has been shown to contribute to cell apoptosis and senescence. It is expected to delay cellular senescence by linking IFN with cellular senescence and studying the effects of IFN on cellular senescence and its mechanism. This article provides a review of the research on the relationship between IFN and cellular senescence by consulting relevant literature.

Recurrence rates after functional surgery versus amputation for nail squamous cell carcinoma not involving the bone: A systematic review.

Background Nail unit squamous cell carcinoma (nSCC) is a malignant subungual tumour. Although it has a low risk of metastasis and mortality, the tumour has a significant local recurrence rate. There is insufficient data to determine whether functional surgery is less effective than amputation for nSCC that does not involve the bone. Objectives We aimed to investigate existing data on the outcomes of functional surgery and amputation for nSCC without bone invasion. Materials and Methods We carried out an extensive search in PubMed, Embase, Cochrane Library, Web of Science, and Scopus for appropriate English-language academic papers, starting with the creation of individual resources until February 23, 2023. The main outcome was local recurrence. Initially, 2191 studies related to nSCC were selected. Information from every research study was retrieved and subdivided, comprising the year of publication, period, number of patients, age, gender distribution, tumour stage, type of intervention, number of recurrences, and follow-up period. Results Ten independent studies (319 lesions) were finally selected. Mohs micrographic surgery was the most reported surgical modality, followed by wide surgical excision and amputation. Local recurrence rates between Mohs micrographic surgery, wide surgical excision and amputation treatment were nearly identical. Other surgical methods included limited surgical excision, partial ablation, and limited excision until the clearing of margins, with recurrence rates up to 50%. Conclusions Given the functional impairment and psychological distress associated with phalanx amputation, functional surgery, including Mohs micrographic surgery and wide surgical excision , should be the preferred therapy for nSCC without bone involvement. Amputation should remain the preferred therapy for nSCC that involves the bone. Partial excision should be avoided. Further studies on whether Mohs micrographic surgery or wide surgical excision is a better option for nSCC not involving the bone are required.

Relationship between Neutrophil-to-Lymphocyte Ratio and Liver Fibrosis in Nonalcoholic Fatty Liver Disease Among Adults in the United States: Data from the National Health and Nutrition Examination Survey 2017-2018.

BACKGROUND/AIMS:  The relationship between neutrophil-to-lymphocyte ratio (NLR) and liver fibrosis in nonalcoholic fatty liver disease remains controversial. The aim of this study was to examine the association between NLR and liver fibrosis. MATERIALS AND METHODS:  We conducted a cross-sectional analysis using the National Health and Nutrition Examination Survey. Vibration-controlled transient elastography was used to assess liver fibrosis and its severity. Neutrophil-to-lymphocyte ratio was calculated as the ratio of neutrophil count to lymphocyte count. RESULTS:  This study included 1620 US adults with a mean age of 52.9 years, of which 53.3% were male. The obese population accounted for 62.5%, 68.5% had hypertension, 31.1% had diabetes, and 16% had significant liver fibrosis. After adjusting for all covariates, a positive correlation was observed between NLR and the severity of liver fibrosis (ß = 0.57, 95% CI = 0.22-0.92, P = .001), which remained stable across different subgroups. CONCLUSION:  This study suggests that elevated NLR levels are positively correlated with the severity of liver fibrosis in patients with nonalcoholic fatty liver disease, and these results can be well generalized to the US adult population.