Intratumoral injection of mRNA encoding survivin in combination with STAT3 inhibitor stattic enhances antitumor effects.

Intratumoral delivery of mRNA encoding immunostimulatory molecules can initiate a robust, global antitumor response with little side effects by enhancing local antigen presentation in the tumor and the tumor draining lymph node. Neoantigen-based mRNA nanovaccine can inhibit melanoma growth in mice by intratumoral injection. Myeloid-derived suppressor cells (MDSCs) suppress antitumor immune responses by secreting immunosuppressive agents, such as reactive oxygen species (ROS). Suppression of STAT3 activity by stattic may reduce MDSC-mediated immunosuppression in the TME and promote the antitumor immune responses. In this study, in vitro transcribed mRNA encoding tumor antigen survivin was prepared and injected intratumorally in BALB/c mice bearing subcutaneous colon cancer tumors. In vivo studies demonstrated that intratumoral survivin mRNA therapy could induce antitumor T cell response and inhibit tumor growth of colon cancer. Depletion of CD8+ T cells could significantly inhibit survivin mRNA-induced antitumor effects. RT-qPCR and ELISA analysis indicated that survivin mRNA treatment led to increased expression of receptor activator nuclear factor-κB ligand (RANKL). In vitro experiment showed that MDSCs could be induced from mouse bone marrow cells by RANKL and RANKL-induced MDSCs could produce high level of ROS. STAT3 inhibitor stattic suppressed activation of STAT3 and NF-κB signals, thereby inhibiting expansion of RANKL-induced MDSCs. Combination therapy of survivin mRNA and stattic could significantly enhance antitumor T cell response, improve long-term survival and reduce immunosuppressive tumor microenvironment compared to each monotherapy. In addition, combined therapy resulted in a significantly reduced level of tumor cell proliferation and an obviously increased level of tumor cell apoptosis in CT26 colon cancer-bearing mice, which could be conducive to inhibit the tumor growth and lead to immune responses to released tumor-associated antigens. These studies explored intratumoral mRNA therapy and mRNA-based combined therapy to treat colon cancer and provide a new idea for cancer therapy.

Heterologous booster vaccination enhances antibody responses to SARS-CoV-2 by improving Tfh function and increasing B-cell clonotype SHM frequency.

Heterologous prime-boost has broken the protective immune response bottleneck of the COVID-19 vaccines. however, the underlying mechanisms have not been fully elucidated. Here, we investigated antibody responses and explored the response of germinal center (GC) to priming with inactivated vaccines and boosting with heterologous adenoviral-vectored vaccines or homologous inactivated vaccines in mice. Antibody responses were dramatically enhanced by both boosting regimens. Heterologous immunization induced more robust GC activation, characterized by increased Tfh cell populations and enhanced helper function. Additionally, increased B-cell activation and antibody production were observed in a heterologous regimen. Libra-seq was used to compare the differences of S1-, S2- and NTD-specific B cells between homologous and heterologous vaccination, respectively. S2-specific CD19+ B cells presented increased somatic hypermutations (SHMs), which were mainly enriched in plasma cells. Moreover, a heterologous booster dose promoted the clonal expansion of B cells specific to S2 and NTD regions. In conclusion, the functional role of Tfh and B cells following SARS-CoV-2 heterologous vaccination may be important for modulating antibody responses. These findings provide new insights for the development of SARS-CoV-2 vaccines that induce more robust antibody response.

Modified approach of regenerative treatment for distal intrabony defect beneath non-keratinized mucosa at terminal molar: A case report.

BACKGROUND: Intrabony defects beneath non-keratinized mucosa are frequently observed at the distal site of terminal molars. Consequently, the application of regenerative treatment using the modified wedge-flap technique is considered impractical for these specific dental conditions. CASE SUMMARY: This article proposes a modified surgical procedure aimed at exposing the distal intrabony defect by making a vertical incision in the keratinized buccal gingiva. The primary objective is to maintain gingival flap stability, thereby facilitating periodontal regeneration. The described technique was successfully employed in a case involving the left mandibular second molar, which presented with an intrabony defect without keratinized gingiva at the distal site. In this case, an incision was made on the disto-buccal gingival tissue, creating a tunnel-like separation of the distal non-keratinized soft tissue to expose the intrabony defect. Subsequently, bone grafting and guided tissue regeneration surgeries were performed, resulting in satisfactory bone fill at 9 mo postoperatively. CONCLUSION: This technique offers a regenerative opportunity for the intrabony defects beneath non-keratinized mucosa and is recommended for further research.

Liver X receptor inverse agonist SR9243 attenuates rheumatoid arthritis via modulating glycolytic metabolism of macrophages.

Liver X receptors (LXRs) which link lipid metabolism and inflammation, were overexpressed in experimental rheumatoid arthritis (RA) rats as observed in our previous studies, while suppression of LXRα by silybin ameliorates arthritis and abnormal lipid metabolism. However, the role of LXRs in RA remains undefined. In this study, we investigated the inhibition role of LXRs in the polarization and activation of M1 macrophage by using a special LXRs inverse agonist SR9243, which led to ameliorating the progression of adjuvant-induced arthritis (AIA) in rats. Mechanistically, SR9243 disrupted the LPS/IFN-γ-induced Warburg effect in M1 macrophages, while glycolysis inhibitor 2-DG attenuated the inhibition effect of SR9243 on M1 polarization and the cytokines expression of M1 macrophages including iNOS, TNF-α, and IL-6 in vitro. Furthermore, SR9243 downregulated key glycolytic enzymes, including LDH-A, HK2, G6PD, GLUT1, and HIF-1α in M1 macrophages, which is mediated by increased phosphorylation of AMPK (Thr172) and reduced downstream phosphorylation of mTOR (Ser2448). Importantly, gene silencing of LXRs compromises the inhibition effect of SR9243 on M1 macrophage polarization and activation. Collectively, for the first time, our findings suggest that the LXR inverse agonist SR9243 mitigates adjuvant-induced rheumatoid arthritis and protects against bone erosion by inhibiting M1 macrophage polarization and activation through modulation of glycolytic metabolism via the AMPK/mTOR/HIF-1α pathway.

Voltage-dependent anion channel 1 mediates mitochondrial fission and glucose metabolic reprogramming in response to ionizing radiation.

The ionizing radiation (IR) represents a formidable challenge as an environmental factor to mitochondria, leading to disrupt cellular energy metabolism and posing health risks. Although the deleterious impacts of IR on mitochondrial function are recognized, the specific molecular targets remain incompletely elucidated. In this study, HeLa cells subjected to γ-rays exhibited concomitant oxidative stress, mitochondrial structural alterations, and diminished ATP production capacity. The γ-rays induced a dose-dependent induction of mitochondrial fission, simultaneously manifested by an elevated S616/S637 phosphorylation ratio of the dynamin-related protein 1 (DRP1) and a reduction in the expression of the mitochondrial fusion protein mitofusin 2 (MFN2). Knockdown of DRP1 effectively mitigated γ-rays-induced mitochondrial network damage, implying that DRP1 phosphorylation may act as an effector of radiation-induced mitochondrial damage. The mitochondrial outer membrane protein voltage-dependent anion channel 1 (VDAC1) was identified as a crucial player in IR-induced mitochondrial damage. The VDAC1 inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), counteracts the excessive mitochondrial fission induced by γ-rays, consequently rebalancing the glycolytic and oxidative phosphorylation equilibrium. This metabolic shift was uncovered to enhance glycolytic capacity, thus fortifying cellular resilience and elevating the radiosensitivity of cancer cells. These findings elucidate the intricate regulatory mechanisms governing mitochondrial morphology under radiation response. It is anticipated that the development of targeted drugs directed against VDAC1 may hold promise in augmenting the sensitivity of tumor cells to radiotherapy and chemotherapy.

The correlation between corona virus disease 2019 and alopecia areata: a literature review.

Corona virus disease 2019(COVID-19) is one of the most serious respiratory pandemic diseases threatening human health for centuries. Alopecia areata (AA) is a sudden patchy hair loss, an autoimmune disease, which seriously affects the image and mental health of patients. Evidence shows that the risk of autoimmune diseases significantly increases after COVID-19, and is positively correlated with the severity, with a significant increase in the risk of alopecia in those over 40 years old. The relationship between COVID-19 and AA has become a hot topic of current research. Strengthening the research on the correlation between COVID-19 and AA can help to identify and protect susceptible populations at an early stage. This article reviews the research progress on the epidemiological background of COVID-19 and AA, the situation and possible mechanisms of AA induced by COVID-19 or COVID-19 vaccination, and potential treatment methods.

A comparative study of dietary amino acid patterns: unveiling growth, composition, and molecular signatures in juvenile Onychostoma macrolepis.

The wild Onychostoma macrolepis, a species under national class II protection in China, lacks a specific compound feed for captive rearing. Understanding the dietary amino acid pattern is crucial for optimal feed formulation. This study aimed to investigate the effects of the four different dietary amino acid patterns, i.e., anchovy fishmeal protein (FMP, control group) and muscle protein (MP), whole-body protein (WBP), fish egg protein (FEP) of juvenile Onychostoma macrolepis, on the growth performance, body composition, intestinal morphology, enzyme activities, and the expression levels of gh, igf, mtor genes in juveniles. In a 12-week feeding trial with 240 juveniles (3.46±0.04g), the MP group demonstrated superior outcomes in growth performance (FBW, WGR, SGR), feed utilization efficiency (PER, PRE, FCR). Notably, it exhibited higher crude protein content in whole-body fish, enhanced amino acid composition in the liver, and favorable fatty acid health indices (AI, TI, h/H) in muscle compared to other groups (P < 0.05). Morphologically, the MP and FMP groups exhibited healthy features. Additionally, the MP group displayed significantly higher activities of TPS, ALP, and SOD, along with elevated expression levels of gh, igf, mtor genes, distinguishing it from the other groups (P < 0.05). This study illustrated that the amino acid pattern of MP emerged as a suitable dietary amino acid pattern for juvenile Onychostoma macrolepis. Furthermore, the findings provide valuable insights for formulating effective feeds in conserving and sustainably farming protected species, enhancing the research's broader ecological and aquacultural significance.

Laser Interference Additive Manufacturing: Mask Bundle Shape Bionic Shark Skin Structure.

Here, we explored a new manufacturing strategy that uses the mask laser interference additive manufacturing (MLIAM) technique, which combines the respective strengths of laser interference lithography and mask lithography to efficiently fabricate across-scales three-dimensional bionic shark skin structures with superhydrophobicity and adhesive reduction. The phenomena and mechanisms of the MLIAM curing process were revealed and analyzed, showing the feasibility and flexibility. In terms of structural performance, the adhesive force on the surface can be tuned based on the growth direction of the bionic shark skin structures, where the maximum rate of the adhesive reduction reaches about 65%. Furthermore, the evolution of the directional diffusion for the water droplet, which is based on the change of the contact angle, was clearly observed, and the mechanism was also discussed by the models. Moreover, no-loss transportations were achieved successfully using the gradient adhesive force and superhydrophobicity on the surface by tuning the growth direction and modifying by fluorinated silane. Finally, this work gives a strategy for fabricating across-scale structures on micro- and nanometers, which have potential application in bioengineering, diversional targeting, and condenser surface.

Comparison of accelerated and standard infliximab induction regimens in acute severe ulcerative colitis using propensity score analysis: a retrospective multicenter study in China.

Background: The optimal regimen of infliximab salvage in acute severe ulcerative colitis (ASUC) patients remains controversial. This study aimed to compare accelerated and standard infliximab induction in Chinese ASUC patients, and to explore risk factors and concrete accelerated regimens for them. Methods: Data were retrospectively collected from steroid-refractory ASUC patients receiving infliximab as rescue therapy at seven tertiary centers across China. Outcomes including colectomy and clinical remission (Mayo score ≤ 2 and every subscore ≤ 1 at Day 14) rates were compared between patients receiving accelerated and standard infliximab induction using propensity score adjustment for potential confounders. The dose-response relationship was explored by plotting restricted cubic splines. Logistic regression and Cox proportional hazards regression analyses were performed to determine risk factors for adverse outcomes. A systematic review and meta-analysis was also performed. Results: A total of 76 patients were analysed: 29 received standard and 47 received accelerated induction. The accelerated group had a higher 90-day colectomy rate (17.8% vs 0%, P = 0.019) and lower clinical remission rate (27.7% vs 65.5%, P = 0.001). After adjusting for propensity score and institution, there was no significant difference in colectomy or clinical remission rates (both P > 0.05). Dose-effect curves showed decreased colectomy hazard with higher cumulative infliximab dosage within 5 days, with no improvement observed for increasing cumulative infliximab dosage within 28 days. Multivariate logistic regression analyses revealed C-reactive protein of >10 mg/L at infliximab initiation (odds ratio = 5.00, 95% confidence interval: 1.27-24.34) as an independent risk factor for no clinical remission. Meta-analysis also revealed no significant difference in colectomy rates at 3 months (P = 0.54). Conclusions: After adjusting for confounders, there were no significant differences in colectomy or clinical remission rates between accelerated and standard infliximab induction among ASUC patients. Early administration of an intensified dosage within 5 days may be beneficial. Elevated C-reactive protein at infliximab initiation indicated need for intensive treatment.

Nd:YVO4/YVO4 cascaded Raman laser pumped dual-wavelength signal wave MgO:PPLN-OPO with wide range adjustable wavelength interval.

This article presents a dual-wavelength signal wave output system capable of generating a broad range of adjustable wavelength intervals. The setup involved the creation of a dual-wavelength cascaded Raman laser featuring composite cavities operating at 1176 nm and 1313 nm. Experimental investigations were carried out on an external cavity MgO:PPLN-OPO driven by the cascaded Raman laser. By setting the crystal polarization period to 27.6-34.4 µm and the temperature to 50-130°C, adjustable tunable output of dual-wavelength signal wave at 1176 nm-MgO:PPLN-OPO (1550-2294 nm) and 1313 nm-MgO:PPLN-OPO (1768-2189 nm) was achieved with a wavelength interval of 0-218 nm. Under the conditions of a period of 34.4 µm, temperature of 90°C, and an incident Raman power of 2.6 W, the highest conversion efficiency of Raman to dual-wavelength signal wave (2212, 2182 nm) was 34.2%. Furthermore, the maximum output power of dual-wavelength signal wave was recorded at 1.02 W with an incident Raman power of 3.33 W.

Efficacy of steam and diatomaceous earth dust against the tropical bed bug Cimex hemipterus (F.) under laboratory and field conditions.

BACKGROUND: Over the past two decades, bed bugs (Cimex spp.) have resurged as common urban pests around the world. The search for efficient and safe control measures has become a key interest among researchers, manufacturers, and pest control professionals. In this study, we evaluated and compared the efficacy of steam, diatomaceous earth (DE) dust, and a combination of both against tropical bed bugs (Cimex hemipterus (F.)) under laboratory and field conditions. RESULTS: In the laboratory study, the mortality of bed bugs after 2 days of exposure to DE dust was 100%. When bed bugs stayed on the surface of an object or in cracks, a brief steam treatment (1 s) caused 100% mortality. However, when bed bugs were hidden under a fabric cover, steam application for 10 s only caused 89 ± 6% mortality. Bed bugs that survived steam treatment exhibited reduced feeding activity. In a 14-week long study, there was no significant difference in the reduction rate of bed bugs between steam treatment and DE dust treatment. A 37-week long control study showed that steam and steam plus DE dust treatments eliminated 97-100% of the infestations. CONCLUSION: Applying steam and DE dust are effective strategies for eliminating natural tropical bed bug infestations. Continuous follow-up monitoring and treatment until no bed bugs are found are crucial in completely eliminating the infestation of tropical bed bugs. © 2024 Society of Chemical Industry.

Adiponectin mRNA Conjugated with Lipid Nanoparticles Specifically Targets the Pathogenesis of Type 2 Diabetes.

Type 2 diabetes (T2D) is a widespread health condition both in the United States and around the world, with insulin resistance playing a critical role in its development. Effective treatment strategies are essential for managing T2D and mitigating associated risks. Adiponectin (APN), secreted by adipocytes, exhibits an inverse correlation with obesity-related adiposity, and its levels are negatively associated with insulin resistance and body mass index. This study aimed to enhance endogenous APN levels in a diet-induced obese (DIO) mouse model using lipid nanoparticles (LNP) as safe delivery agents for APN mRNA conjugates. The results indicate that APN-mRNA-LNP administration successfully induced APN synthesis in various tissues, including muscle, liver, kidney, pancreas, and adipose cells. This induction was associated with several positive outcomes, such as preventing diet-induced body weight gain, improving hyperglycemia by promoting Glut-4 expression, alleviating diabetic nephropathy symptoms by blocking the EGFR pathway, and reducing pro-inflammatory cytokine production. In addition, the treatment demonstrated enhanced insulin sensitivity by activating DGKd and inhibiting PKCε. This resulted in reactivation of insulin receptors in insulin target tissues and stimulation of insulin secretion from pancreatic beta cells. The findings of the present study highlight the potential of APN-mRNA-LNP-based nucleic acid therapy as a treatment for type 2 diabetes, offering a comprehensive approach to addressing its complexities.

Synergy of higher education resources and digital infrastructure construction in China: Regional differences, dynamic evolution and trend forecasting.

The deep integration of higher education with digital technology represents an inevitable trend, and evaluating the interplay between higher education resources (HER) and digital infrastructure construction (DIC) holds significant value for advancing the development of digital higher education and mitigating regional disparities in China. This study establishes two comprehensive evaluation frameworks for HER and DIC. Panel data from 31 provinces, spanning the period from 2011 to 2020, are utilized for analysis. The coupling coordination degree (CCD) model is employed in this work to evaluate the synergy between HER and DIC in China. Furthermore, we analyze the regional differences, spatial distribution, and trend evolution of this synergy. The study results revealed that there is an initial decrease followed by an increase in the synergy between HER and DIC, and the overall CCD is at a moderate coordination, with the mean CCD of the eastern region being significantly higher than that of the other three regions, and the inter-regional difference is the main source of regional disparity in this synergy. The current state of synergistic development reveals a slight inclination towards multi-polarization, although the disparity in regional development was decreasing. Additionally, there is an observed convergence in the coordinated development of HER and DIC, with spatial factors playing a significant role. These findings offer empirical support for efforts to enhance the integration of HER and DIC, reduce regional disparities in higher education, and foster sustainable development in China's higher education sector.

Grape seed extract prevents oestrogen deficiency-induced bone loss by modulating the gut microbiota and metabolites.

Proanthocyanidin-rich grape seed extract (GSE) has been shown to have the potential to protect bones, although the underlying mechanism remains unknown. The current study aims to explore GSE's preventive and therapeutic impact on bone loss induced by oestrogen deficiency and the underlying mechanism through the gut microbiota (GM) and metabolomic responses. In oestrogen-deficient ovariectomized (OVX) mice, GSE ameliorated bone loss by inhibiting the expansion of bone marrow adipose tissue (BMAT), restoring BMAT lipolysis and promoting bone formation. GSE regulated OVX-induced GM dysbiosis by reducing the abundance of opportunistic pathogenic bacteria, such as Alistipes, Turicibacter and Romboutsia, while elevating the abundance of beneficial bacteria, such as Bifidobacterium. The modified GM primarily impacted lipid and amino acid metabolism. Furthermore, the serum metabolites of GSE exhibited a significant enrichment in lipid metabolism. In summary, GSE shows potential as a functional food for preventing oestrogen deficiency-induced bone loss by modulating GM and metabolite-mediated lipid metabolism.

A quick paster type of soluble nanoparticle microneedle patch for the treatment of obesity.

Obesity is a major public burden on the working population and induces chronic diseases. Its treatment often requires long-term medication, which makes patient compliance difficult. In this study, we reported the value of HORN-MN, which comprised a fast-soluble hyaluronic acid microneedle matrix and a weak acid-degradable oleanolic acid dimer of rosiglitazone nanoparticles. The results showed that the microneedles easily punctured the stratum corneum and dissolved in the dermis of the abdominal wall within 5 min, followed by the release of rosiglitazone nanoparticles. Thereafter, the nanoparticles were endocytosed by macrophages and white adipocytes, then degraded to oleanolic acid in the lysosomes, thereby, releasing rosiglitazone. Oleanolic acid significantly improved the inflammatory status of obese adipose tissue and promoted white adipocyte browning, and rosiglitazone significantly potentiated WAC browning. Accordingly, the patch demonstrated a remarkable obesity-reducing efficacy in mice. In conclusion, this study developed a quick paster type of soluble rosiglitazone nanoparticle microneedle for the treatment of obesity. This patch can be suitable for working people, with an evident obesity-reducing efficacy but no effect on skin integrity despite multiple administrations.

Efficacy and Safety of Remimazolam Versus Etomidate for Induction of General Anesthesia: Protocol for a Systematic Review and Meta-Analysis.

BACKGROUND: Postinduction hypotension (PIHO) is a hemodynamic abnormality commonly observed during the induction of general anesthesia. Etomidate is considered a safer drug for the induction of anesthesia because it has only minor adverse effects on the cardiovascular and pulmonary systems. Recent evidence indicates that the novel benzodiazepine remimazolam has minimal inhibitory effects on the circulation and respiration. However, the efficacy and safety of remimazolam versus etomidate in the induction of anesthesia are unclear. OBJECTIVE: To further understand the potential of remimazolam in anesthesia induction, it is necessary to design a meta-analysis to compare its effects versus the classic safe anesthetic etomidate. The aim of this study is to determine which drug has more stable hemodynamics and a lower incidence of PIHO. Our study will also yield data on sedation efficiency, time to loss of consciousness, time to awakening, incidence of injection pain, and postoperative nausea and vomiting with the two drugs. METHODS: We plan to search the Web of Science, Cochrane Library, Embase, PubMed, China National Knowledge Infrastructure, and Wanfang databases from the date of their creation until March 31, 2025. The language is limited to English and Chinese. The search terms are "randomized controlled trials," "etomidate," and "remimazolam." The incidence of PIHO is the primary outcome measure. Secondary outcomes include depth of anesthesia after induction, sedation success rate, time to loss of consciousness, hemodynamic profiles, recovery time, incidence of injection pain, and postoperative nausea and vomiting. Reviews, meta-analyses, case studies, abstracts from conferences, and commentaries will not be included. The heterogeneity of the results will be evaluated by sensitivity and subgroup analyses. RevMan software and Stata software will be used for data analysis. We will evaluate the quality of included studies using version 2 of the Cochrane risk-of-bias tool. The confidence of the evidence will be assessed through the Grading of Recommendations, Assessments, Developments, and Evaluations system. RESULTS: The protocol was registered in the international PROSPERO (Prospective Register of Systematic Reviews) registry in November 2023. As of June 2024, we have performed a preliminary article search and retrieval for further review. The review and analyses are expected to be completed in March 2025. We expect to submit manuscripts for peer review by the end of June 2025. CONCLUSIONS: By synthesizing the available evidence and comparing remimazolam and etomidate, we hope to provide valuable insights into the selection of anesthesia-inducing drugs to reduce the incidence of PIHO and improve patient prognosis. TRIAL REGISTRATION: PROSPERO CRD42023463120; https://tinyurl.com/333jb8bm. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/55948.

Long-term success and influencing factors of regenerative surgery for intra-bony defects: A retrospective cohort study.

BACKGROUND: The composite outcome measure (COM) more comprehensively assesses the clinical efficacy of regenerative surgery than a single probing measurement. We aimed to assess long-term success defined by the COM (clinical attachment level [CAL] gain of ≥3 mm and postsurgery probing pocket depth [PPD] ≤ 4 mm) and influencing factors of regenerative surgery using bone substitutes and resorbable collagen membrane (RM) for intra-bony defects (IBDs). METHODS: We retrospectively collected data from patients who underwent regenerative surgery using deproteinized bovine bone mineral (DBBM) and RM for IBDs. CAL and PPD values were compared at baseline (preoperative), 1 year (short-term), and at the last follow-up (5-10 years). Multivariate logistic regressions were performed to identify factors influencing COM-based long-term success. RESULTS: Eighty-one defects in 75 teeth of 33 patients who completed follow-up (6.5 ± 1.4 years) were included. One tooth was lost. All defects with complete follow-up exhibited long-term average CAL gain (3.00 ± 2.00 mm, 95% confidence interval [CI]: 2.56-3.44 mm, p < 0.001) and PPD reduction (2.06 ± 1.91 mm, 95% CI: 1.64-2.49 mm, p < 0.001). Long-term success was achieved in 38.8% of IBDs. CAL and PPD values were comparable between 1 year and the last follow-up. Logistic regression analyses revealed that male sex (odds ratio [OR] = 0.23, 95% CI: 0.07-0.75) and bleeding on probing (BOP) during supportive periodontal therapy (OR = 0.96, 95% CI: 0.94-0.99) were risk factors for long-term success. CONCLUSIONS: Regenerative surgery with DBBM and RM for IBDs can achieve some degree of long-term success defined by COM. However, within this study's limitations, male sex and higher BOP incidence postoperatively are negatively associated with optimal long-term success. CLINICAL TRIAL NUMBER: ChiCTR2300069016.

Factors influencing the outcomes of dermatoses during the COVID-19 outbreak in China: a retrospective study.

Background: The coronavirus disease 2019 (COVID-19) pandemic subverted people's lives and potentially affected the management and prognosis of pre-existing dermatoses. The study aims to identify factors influencing the outcomes of dermatoses during a rapid and widespread Omicron outbreak in China following the adjustment of the COVID-19 policy. Materials and methods: This retrospective observational study involved outpatients visiting the dermatology department at a tertiary referral hospital in Beijing, China between December 2022 and February 2023. Demographics, COVID-19 characteristics, treatment modalities, and dermatosis outcomes were subjected to statistical analysis. Results: The odds ratio (OR) for vitiligo aggravation during COVID-19 was 0.497 [95% confidence interval (CI): 0.254-0.973, p = 0.038] compared to total patients with various dermatoses. Psoriasis patients with a maximum body temperature (Tmax) over 38.6°C during COVID-19 were 2.833 times more likely to experience dermatosis aggravation (OR: 2.833 [1.029-7.803], p = 0.041). Moreover, autoimmune bullous disease (AIBD) patients receiving biologics treatment exhibited a reduced likelihood of aggravation during the COVID-19 outbreak (OR: 0 [0-0.531], p = 0.011). Conclusion: Vitiligo exhibits lower aggravation rates during COVID-19 than other dermatoses. A higher body temperature during COVID-19 infection can increase the risk of psoriasis aggravation. Biologics treatment reduces the risk of AIBD aggravation during the COVID-19 outbreak.

The combination of metabolome and transcriptome clarifies the inhibition of the Alternaria toxin accumulation by methyl ferulate.

As one of the most typical pathogens in fruit postharvest diseases, Alternaria alternata (A. alternata) can produce Alternaria toxins (ATs) aggravating fruit decay and harming human health. In this study, ATs (tenuazonic acid, alternariol monomethyl ether, and alternariol) production was inhibited effectively by 200 and 8000 mg/L MF (methyl ferulate) in vitro and in vivo. 1-Octen-3-ol and 3-octanol were the potential iconic volatile organic compounds of ATs (R2 > 0.99). MF induced oxidative stress, resulting in physiological and metabolic disorders, membrane lipid oxidation and cell damage. It decreased precursors and energy supply by disturbing amino acid metabolism, ABC transporters, citrate cycle, pentose and glucuronate interconversions to regulate ATs synthesis. MF down-regulated the genes related to ATs synthesis (PksJ, AaTAS1, and OmtI), transport (AaMFS1 and MFS), and pathogenicity to affect ATs production and virulence. This study provided a theoretical basis for the control of ATs production.