Sarcopenia is associated with short- and long-term mortality in patients with acute-on-chronic liver failure.

BACKGROUND: While sarcopenia is recognized as a predictor of mortality in cirrhosis, its influence on acute-on-chronic liver failure (ACLF) remains uncertain. Despite multiple studies examining the impact of sarcopenia on short-term mortality in patients with ACLF, the sample size of these studies was limited, and their outcomes were inconsistent. Therefore, this study aimed to explore the impact of sarcopenia on both short- and long-term mortality in patients with ACLF. METHODS: This retrospective cohort study included 414 patients with ACLF that were treated between January 2016 and September 2022. Sarcopenia was diagnosed based on the measurement of the skeletal muscle index at the third lumbar vertebra (L3-SMI). Subsequently, the patients were divided into sarcopenia and non-sarcopenia groups. We analysed the basic clinical data of the two groups. Multivariate Cox proportional analysis was used to analyse short-term (28 days) and long-term (1 year and overall) mortality rates. RESULTS: A total of 414 patients were included, with a mean age of 52.88 ± 13.41 years. Among them, 318 (76.8%) were male, and 239 (57.7%) had sarcopenia. A total of 280 (67.6%) patients died during the study period. Among them, 153 patients died within 28 days (37%) and 209 patients died within 1 year (50.5%). We found that the 28-day, 1-year and overall mortality rates in the sarcopenia group were significantly higher than those in the non-sarcopenia group (37% vs. 22.3%, P < 0.01; 50.5% vs. 34.9%, P < 0.01; and 67.6% vs. 53.1%, P < 0.01, respectively). Multivariate Cox regression analysis revealed that sarcopenia was significantly associated with increased mortality. The hazard ratios for sarcopenia were 2.05 (95% confidence interval [CI] 1.41-3.00, P < 0.01) for 28-day mortality, 1.81 (95% CI 1.29-2.54, P < 0.01) for 1-year mortality and 1.82 (95% CI 1.30-2.55, P < 0.01) for overall mortality. In addition, muscle density and international normalized ratio were associated with short- and long-term mortality. CONCLUSIONS: Sarcopenia is associated with both short- and long-term mortality in patients with ACLF. Therefore, regular monitoring for sarcopenia is important for these patients.

KLHL21 suppresses gastric tumourigenesis via maintaining STAT3 signalling equilibrium in stomach homoeostasis.

OBJECTIVE: Precancerous metaplasia transition to dysplasia poses a risk for subsequent intestinal-type gastric adenocarcinoma. However, the molecular basis underlying the transformation from metaplastic to cancerous cells remains poorly understood. DESIGN: An integrated analysis of genes associated with metaplasia, dysplasia was conducted, verified and characterised in the gastric tissues of patients by single-cell RNA sequencing and immunostaining. Multiple mouse models, including homozygous conditional knockout Klhl21-floxed mice, were generated to investigate the role of Klhl21 deletion in stemness, DNA damage and tumour formation. Mass-spectrometry-based proteomics and ribosome sequencing were used to elucidate the underlying molecular mechanisms. RESULTS: Kelch-like protein 21 (KLHL21) expression progressively decreased in metaplasia, dysplasia and cancer. Genetic deletion of Klhl21 enhances the rapid proliferation of Mist1+ cells and their descendant cells. Klhl21 loss during metaplasia facilitates the recruitment of damaged cells into the cell cycle via STAT3 signalling. Increased STAT3 activity was confirmed in cancer cells lacking KLHL21, boosting self-renewal and tumourigenicity. Mechanistically, the loss of KLHL21 promotes PIK3CB mRNA translation by stabilising the PABPC1-eIF4G complex, subsequently causing STAT3 activation. Pharmacological STAT3 inhibition by TTI-101 elicited anticancer effects, effectively impeding the transition from metaplasia to dysplasia. In patients with gastric cancer, low levels of KLHL21 had a shorter survival rate and a worse response to adjuvant chemotherapy. CONCLUSIONS: Our findings highlighted that KLHL21 loss triggers STAT3 reactivation through PABPC1-mediated PIK3CB translational activation, and targeting STAT3 can reverse preneoplastic metaplasia in KLHL21-deficient stomachs.

Design, synthesis, and anti-oomycete activity of 3-acyloxymaltol/ethyl maltol derivatives.

Twenty 3-acyloxymaltol/ethyl maltol derivatives (7a-j and 8a-j) were synthesized and evaluated in vitro for their anti-oomycete activity against Phytophthora capsici, respectively. Among all of twenty derivatives, more than half of the compounds 7f, 7h, 8a-h and 8j had anti-oomycete activity higher than the positive control zoxamide (EC50 = 22.23 mg/L), and the EC50 values of 18.66, 20.32, 12.80, 16.18, 10.59, 14.98, 16.80, 10.36, 15.32, 12.64, and 13.59 mg/L, respectively. Especially, compounds 8c and 8f exhibited the best anti-oomycete activity against P. capsici with EC50 values of 10.59 and 10.36 mg/L, respectively. Overall, hydroxyl group of maltol/ethyl maltol is important active modification site.

Is refractive error a factor affecting scoliosis?

BACKGROUND: Scoliosis is one of the most common surgical disorders of the pediatric spine. Refractive errors are commonly associated with vision impairment worldwide. However, it is currently unclear whether refractive error correlates directly with the development of scoliosis. METHODS: A cross-sectional study was performed in 2023, and a stratified cluster sampling technique was employed among school-aged students in Nantong City, China. Univariate and multivariate logistic regression analyses were used to investigate specific correlations between scoliosis and related parameters; various types of refractive errors were also included in the study. RESULTS: The prevalence of scoliosis among school-aged students was 2.2% in Nantong city. Multiple logistic regression analyses showed that myopia, hyperopia, astigmatism, and anisometropia were not correlated with the development of scoliosis (all, p≥0.05). Lower body mass index (BMI) [adjusted odds ratio (aOR) = 0.92; 95% confidence interval (CI): 0.88-0.95; p<0.001], living in rural areas (aOR = 1.40; 95% CI: 1.05-1.86; p = 0.020), and older age (aOR = 1.32; 95% CI: 1.25-1.38; p<0.001) had significantly higher risks of scoliosis. CONCLUSIONS: Refractive errors did not correlate with the development of scoliosis. However, BMI, living in rural areas and older age did correlate with the development of scoliosis.

CXCL8 Knockout: A Key to Resisting Pasteurella multocida Toxin-Induced Cytotoxicity.

Pasteurella multocida, a zoonotic pathogen that produces a 146-kDa modular toxin (PMT), causes progressive atrophic rhinitis with severe turbinate bone degradation in pigs. However, its mechanism of cytotoxicity remains unclear. In this study, we expressed PMT, purified it in a prokaryotic expression system, and found that it killed PK15 cells. The host factor CXCL8 was significantly upregulated among the differentially expressed genes in a transcriptome sequencing analysis and qPCR verification. We constructed a CXCL8-knockout cell line with a CRISPR/Cas9 system and found that CXCL8 knockout significantly increased resistance to PMT-induced cell apoptosis. CXCL8 knockout impaired the cleavage efficiency of apoptosis-related proteins, including Caspase3, Caspase8, and PARP1, as demonstrated with Western blot. In conclusion, these findings establish that CXCL8 facilitates PMT-induced PK15 cell death, which involves apoptotic pathways; this observation documents that CXCL8 plays a key role in PMT-induced PK15 cell death.

Involvement of E3 ubiquitin ligase NEDD4-mediated YY1 ubiquitination in alleviating idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic and lethal lung disease characterized by progressive lung scarring. This study aims to elucidate the role of the E3 ubiquitin ligase NEDD4 in the ubiquitination of YY1 and its subsequent impact on TAB1 transcription, revealing a possible molecular mechanism in the development of IPF. Through bioinformatics analysis and both in vitro and in vivo experiments, we observed differential expression levels of NEDD4 and YY1 between normal and IPF samples, identifying NEDD4 as an upstream E3 ubiquitin ligase of YY1. Furthermore, binding sites for the transcription factor YY1 on the promoter region of TAB1 were discovered, indicating a direct interaction. In vitro experiments using HEPF cells showed that NEDD4 mediates the ubiquitination and degradation of YY1, leading to suppressed TAB1 transcription, thereby inhibiting cell proliferation and fibrogenesis. These findings were corroborated by in vivo experiments in an IPF mouse model, where the ubiquitination pathway facilitated by NEDD4 attenuated IPF progression through the downregulation of YY1 and TAB1 transcription. These results suggest that NEDD4 plays a crucial role in the development of IPF by modulating YY1 ubiquitination and TAB1 transcription, providing new insights into potential therapeutic targets for treating IPF.

Proteomics screening after pediatric allogenic hematopoietic stem cell transplantation reveals an association between increased expression of inhibitory receptor FCRL6 on γδ T cells and cytomegalovirus reactivation.

We studied the associations between inflammation-related proteins in circulation and complications after pediatric allogenic hematopoietic stem cell transplantation (HSCT), to reveal proteomic signatures or individual soluble proteins associated with specific complications after HSCT. We used a proteomics method called Proximity Extension Assay to repeatedly measure 180 different proteins together with clinical variables, cellular immune reconstitution and blood viral copy numbers in 27 children (1-18 years of age) during a 2-year follow-up after allogenic HSCT. Protein profile analysis was performed using unsupervised hierarchical clustering and a regression-based method, while the Bonferroni-corrected Mann-Whitney U-test was used for time point-specific comparison of individual proteins against outcome. At 6 months after allogenic HSCT, we could identify a protein profile pattern associated with occurrence of the complications such as chronic graft-versus-host disease, viral infections, relapse and death. When protein markers were analyzed separately, the plasma concentration of the inhibitory and cytotoxic T-cell surface protein FCRL6 (Fc receptor-like 6) was higher in patients with cytomegalovirus (CMV) viremia [log2-fold change 1.5 (P = 0.00099), 2.5 (P = 0.00035) and 2.2 (P = 0.045) at time points 6, 12 and 24 months]. Flow cytometry confirmed that FCRL6 expression was higher in innate-like γδ T cells, indicating that these cells are involved in controlling CMV reactivation in HSCT recipients. In conclusion, the potentially druggable FCRL6 receptor on cytotoxic T cells appears to have a role in controlling CMV viremia after HSCT. Furthermore, our results suggest that system-level analysis is a useful addition to the studying of single biomarkers in allogenic HSCT.

Circ-0075305 hinders gastric cancer stem cells by indirectly disrupting TCF4-ß-catenin complex and downregulation of SOX9.

CircRNAs are covalently closed, single-stranded RNA that form continuous loops and play a crucial role in the initiation and progression of tumors. Cancer stem cells (CSCs) are indispensable for cancer development; however, the regulation of cancer stem cell-like properties in gastric cancer (GC) and its specific mechanism remain poorly understood. We elucidate the specific role of Circ-0075305 in GC stem cell properties. Circ-0075305 associated with chemotherapy resistance was identified by sequencing GC cells. Subsequent confirmation in both GC tissues and cell lines revealed that patients with high expression of Circ-0075305 had significantly better overall survival (OS) rates than those with low expression, particularly when treated with postoperative adjuvant chemotherapy for GC. In vitro and in vivo experiments confirmed that overexpression of Circ-0075305 can effectively reduce stem cell-like properties and enhance the sensitivity of GC cells to Oxaliplatin compared with the control group. Circ-0075305 promotes RPRD1A expression by acting as a sponge for corresponding miRNAs. The addition of LF3 (a ß-catenin/TCF4 interaction antagonist) confirmed that RPRD1A inhibited the formation of the TCF4-ß-catenin transcription complex through competitive to ß-catenin and suppressed the transcriptional activity of stem cell markers such as SOX9 via the Wnt/ß-catenin signaling pathway. This leads to the downregulation of stem cell-like property-related markers in GC. This study revealed the underlying mechanisms that regulate Circ-0075305 in GCSCs and suggests that its role in reducing ß-catenin signaling may serve as a potential therapeutic candidate.

Optimisation of hypocrellin production in Shiraia-like fungi via genetic modification involving a transcription factor gene and a putative monooxygenase gene.

Shiraia-like fungi, which are rare parasitic fungi found around bamboo, play an important role in traditional medicine. Their main active component, hypocrellin, is widely used in medicine, food, and cosmetics. By comparing strains with different hypocrellin yields, we identified a transcription factor (SbTF) in the hypocrellin biosynthesis pathway. SbTF from high-yielding zzz816 and low-yielding CNUCC C72 differed in its protein structure. Subsequently, SbTF from high-yielding zzz816 was overexpressed in several strains. This stabilised the yield in zzz816 and significantly increased the yield in low-yielding CNUCC C72. Comparing downstream non-essential genes between wild type and SbTF-overexpressing CNUCC C72 showed that SbMNF was significantly up-regulated. Therefore, it was selected for further study. SbMNF overexpression increased the hypocrellin yield in low-yielding CNUCC C72 and altered the composition of compounds in high-yielding CNUCC 1353PR and zzz816. This involved an increased elsinochrome C yield in CNUCC 1353PR and an increased hypocrellin B yield in zzz816 (by 2 and 70.3 times that in the corresponding wild type, respectively). This study is the first to alter hypocrellin synthesis to alter the levels of one bioactive agent compared to another. The results provide new insights regarding genetic modification and will help to optimise fungal fermentation.

EspP2 Regulates the Adhesion of Glaesserella parasuis via Rap1 Signaling Pathway.

Different levels of EspP2 expression are seen in strains of Glaesserella parasuis with high and low pathogenicity. As a potential virulence factor for G. parasuis, the pathogenic mechanism of EspP2 in infection of host cells is not clear. To begin to elucidate the effect of EspP2 on virulence, we used G. parasuis SC1401 in its wild-type form and SC1401, which was made EspP2-deficient. We demonstrated that EspP2 causes up-regulation of claudin-1 and occludin expression, thereby promoting the adhesion of G. parasuis to host cells; EspP2-deficiency resulted in significantly reduced adhesion of G. parasuis to cells. Transcriptome sequencing analysis of EspP2-treated PK15 cells revealed that the Rap1 signaling pathway is stimulated by EspP2. Blocking this pathway diminished occludin expression and adhesion. These results indicated that EspP2 regulates the adhesion of Glaesserella parasuis via Rap1 signaling pathway.

Prevalence and risk factors for isolated systolic hypertension among the oldest-old population in southwestern China: A community-based cross-sectional study.

The prevalence of isolated systolic hypertension (ISH) has doubled between 2002-2005 and 2014 among the oldest-old population in China. However, the prevalence and characteristics of ISH among the oldest-old population in southwestern China remain less known. This study aimed to investigate the prevalence of ISH among the oldest-old population in Chengdu and identify associated factors to provide valuable information for disease etiology and prevention. We recruited 1,312 participants aged over 80 years by using a stratified cluster sampling method between September 2015 and June 2016, from three districts (Jinjiang, Qingyang, and Longquanyi) of Chengdu, the largest city of southwest China. A structured questionnaire, anthropometric data, and blood pressure were collected according to the standard method. Blood pressure was measured three times by using a standardized mercury sphygmomanometer after a 10-minute seated rest. Of 1312 participants, 53.0% (n = 695) had ISH. The prevalence of ISH in men and women was 54.7% and 51.3%, respectively, with no significant sex difference (P = .222). The prevalence of ISH increased with advanced age in men (P for trend = 0.029), 52.5% for the 80-84 years group, 55.2% for the 85-89 years group, and 70.4% for the 90-98 years group, respectively. Multivariable logistic regression analyses found that drinking (OR = 1.85, 95%CI = 1.26-2.71), being overweight (OR = 1.88, 95%CI = 1.19-2.96), and having a higher heart rate (OR = 0.66, 95%CI = 0.51-0.86) were associated with ISH. Stratified by sex, these three factors remained significant in men. Our work highlights that the burden of ISH is substantial among the oldest-old population in southwestern China.

Sialic acids as attachment factors in mosquitoes mediating Japanese encephalitis virus infection.

The role of Culex mosquitoes in the transmission of Japanese encephalitis virus (JEV) is crucial, yet the mechanisms of JEV infection in these vectors remain unclear. Previous research has indicated that various host factors participate in JEV infection. Herein, we present evidence that mosquito sialic acids enhance JEV infection both in vivo and in vitro. By treating mosquitoes and C6/36 cells with neuraminidase or lectin, the function of sialic acids is effectively blocked, resulting in significant inhibition of JEV infection. Furthermore, knockdown of the sialic acid biosynthesis genes in Culex mosquitoes also leads to a reduction in JEV infection. Moreover, our research revealed that sialic acids play a role in the attachment of JEV to mosquito cells, but not in its internalization. To further explore the mechanisms underlying the promotion of JEV attachment by sialic acids, we conducted immunoprecipitation experiments to confirm the direct binding of sialic acids to the last α-helix in JEV envelope protein domain III. Overall, our study contributes to a molecular comprehension of the interaction between mosquitoes and JEV and offers potential strategies for preventing the dissemination of flavivirus in natural environments.IMPORTANCEIn this study, we aimed to investigate the impact of glycoconjugate sialic acids on mosquito infection with Japanese encephalitis virus (JEV). Our findings demonstrate that sialic acids play a crucial role in enhancing JEV infection by facilitating the attachment of the virus to the cell membrane. Furthermore, our investigation revealed that sialic acids directly bind to the final α-helix in the JEV envelope protein domain III, thereby accelerating virus adsorption. Collectively, our results highlight the significance of mosquito sialic acids in JEV infection within vectors, contributing to a better understanding of the interaction between mosquitoes and JEV.

Case Report: Can preoperative implantation of veno-arterial extracorporeal membrane oxygenation lead to embolic events in infective endocarditis?

Early-stage infective endocarditis (IE) can lead to severe complications, including infarctions and metastatic infections caused by inflammatory embolus shedding. Common embolism sites include the brain, spleen, kidneys, lungs, and intestines. Additionally, acute heart failure (AHF) can occur in up to 40% of cases, and its presence can impact the clinical outcomes of patients with IE. Cardiogenic shock (CGS) is often more likely to occur after AHF has taken place. If bacteria invade the blood, infectious shock can occur. Patients with IE can experience simple CGS, septic shock, or a combination of the two. Extracorporeal membrane oxygenation (ECMO) typically serves as a Bridge for Heart failure and Cardiogenic shock. Previous research indicates that there are limited reports of ECMO support for patients with IE after CGS has occurred. Because CGS may occur at any time during IE treatment, it is important to understand the timing of ECMO auxiliary support and how to carry out comprehensive treatment after support. Timely treatment can help to reduce or avoid the occurrence of serious complications and improve the prognosis of patients with IE. Our work combines a case study to review the ECMO support of IE patients after CGS through a literature review. Overall, we suggest that when patients with IE have large bacterial thrombosis and a greater risk of shedding, it is recommended to carefully evaluate the indications and contraindications for ECMO after discussion by a multidisciplinary team (MDT). Still, active surgical treatment at an early stage is recommended.

Composition analysis of renal and ureteral calculi in a single center in northern China in the past decade.

The current report aimed to evaluate the characteristics of stone composition in 3637 renal and ureteral calculi patients in a single center while clarifying its relationship with sex, age, and time. Out of 3637 cases of upper urinary tract stones, stone specimens were analyzed retrospectively. There were 2373 male patients aged 6 months-87 years, with an average age of 44.73 ±â€…15.63 years, and 1264 female patients aged 4 months-87 years, with an average age of 46.84 ±â€…16.00 years. The male-female ratio was 1.88:1. Five hundred twelve patients had ureteral calculi, and 3125 had renal calculi. The SPSS software helped analyze the relationship between renal and ureteral calculi composition and sex, age, and time. Stone composition demonstrated 2205 cases of calcium oxalate stones (60.6%), 518 carbonate apatite (14.2%), 386 uric acids (10.6%), 232 magnesium ammonium phosphate (6.4%), 117 calcium phosphate (3.2%), 76 cystine (2.1%), 47 sodium urate (1.3%), 31 others (0.9%), and 25 ammonium urate (0.7%) cases. The overall male-to-female sex ratio was 1.88:1. Stones in the upper urinary tract were significantly more frequent in men than in women between the ages of 31 and 60. However, such stones were significantly more frequent in women than men over 80 (P < .05). Cystine, Sodium urate, Carbonated apatite, and uric acid indicated significant differences between different age categories (all P < .001). Stone composition analyses revealed that the frequency of calcium oxalate calculi has increased annually, while cystine and carbonated apatite incidences have dropped annually over the past decade. The components of renal and ureteral calculi vary significantly based on age and sex, with calcium oxalate calculi being more frequent in men while magnesium ammonium phosphate stones are more frequent in female patients. The age between 31 and 60 years is the most prevalent for renal and ureteral calculi in men and women.

Recent progress in ion-regulated organic room-temperature phosphorescence.

Organic room-temperature phosphorescence (RTP) materials have attracted considerable attention for their extended afterglow at ambient conditions, eco-friendliness, and wide-ranging applications in bio-imaging, data storage, security inks, and emergency illumination. Significant advancements have been achieved in recent years in developing highly efficient RTP materials by manipulating the intermolecular interactions. In this perspective, we have summarized recent advances in ion-regulated organic RTP materials based on the roles and interactions of ions, including the ion-π interactions, electrostatic interactions, and coordinate interactions. Subsequently, the current challenges and prospects of utilizing ionic interactions for inducing and modulating the phosphorescent properties are presented. It is anticipated that this perspective will provide basic guidelines for fabricating novel ionic RTP materials and further extend their application potential.

Ultrasound-driven radical chain reaction and immunoregulation of piezoelectric-based hybrid coating for treating implant infection.

The poor efficiency of US-responsive coatings on implants restricts their practical application. Immunotherapy that stimulates immune cells to enhance their antibacterial activity is expected to synergize with sonodynamic therapy for treating implant infection effectively and safely. Herein, US-responsive hybrid coatings composed of the oxygen-deficient BaTiO3 nanorod arrays and l-arginine (BaTiO3-x/LA) are designed and prepared on titanium implants for sonocatalytic therapy-cooperated immunotherapy to treat Methicillin-resistant Staphylococcus aureus (MRSA) infection. BaTiO3-x/LA can generate more oxidizing reactive oxygen species (ROS, hydroxyl radical (·OH)) and reactive nitrogen species (RNS, peroxynitrite anion (ONOO-)). The construction of nanorod arrays and oxygen defects balances the piezoelectric properties and sonocatalytic capability during US treatment. The generated piezoelectric electric field provides a sufficient driving force to separate electrons and holes, and the oxygen defects attenuate the electron-hole recombination efficiency, consequently increasing the yield of ROS during the US treatment. Moreover, nitric oxide (NO) released by l-arginine reacts with the superoxide radical (·O2-) to produce ONOO-. Since, this radical chain reaction improves the oxidizing ability between bacteria and radicals, the cell membrane (argB, secA2) and DNA (dnaBGXN) are destroyed. The bacterial self-repair mechanism indirectly accelerates bacterial death based on the transcriptome analysis. In addition to participating in the radical chain reaction, NO positively affects macrophage M1 polarization to yield potent phagocytosis to MRSA. As a result, without introducing an extra sonosensitizer, BaTiO3-x/LA exhibits excellent antibacterial activity against MRSA after the US treatment for 15 min. Furthermore, BaTiO3-x/LA facilitates macrophage M2 polarization after implantation and improves osteogenic differentiation. The combined effects of sonodynamic therapy and immunoregulation lead to an effective and safe treatment method for implant-associated infections.

Predicting intubation for intensive care units patients: A deep learning approach to improve patient management.

OBJECTIVE: For patients in the Intensive Care Unit (ICU), the timing of intubation has a significant association with patients' outcomes. However, accurate prediction of the timing of intubation remains an unsolved challenge due to the noisy, sparse, heterogeneous, and unbalanced nature of ICU data. In this study, our objective is to develop a workflow for pre-processing ICU data and to develop a customized deep learning model to predict the need for intubation. METHODS: To improve the prediction accuracy, we transform the intubation prediction task into a time series classification task. We carefully design a sequence of data pre-processing steps to handle the multimodal noisy data. Firstly, we discretize the sequential data and address missing data using interpolation. Next, we employ a sampling strategy to address data imbalance and standardize the data to facilitate faster model convergence. Furthermore, we employ the feature selection technique and propose an ensemble model to combine features learned by different deep learning models. RESULTS: The performance is evaluated on Medical Information Mart for Intensive Care (MIMIC)-III, an ICU dataset. Our proposed Deep Feature Fusion method achieves an area under the curve (AUC) of the receiver operating curve (ROC) of 0.8953, surpassing the performance of other deep learning and traditional machine learning models. CONCLUSION: Our proposed Deep Feature Fusion method proves to be a viable approach for predicting intubation and outperforms other deep learning and classical machine learning models. The study confirms that high-frequency time-varying indicators, particularly Mean Blood Pressure (MeanBP) and peripheral oxygen saturation (SpO2), are significant risk factors for predicting intubation.

Puerarin-Loaded Electrospun Patches with Anti-Inflammatory and Pro-Collagen Synthesis Properties for Pelvic Floor Reconstruction.

Pelvic organ prolapse (POP) is one of the most common pelvic floor dysfunction disorders worldwide. The weakening of pelvic connective tissues initiated by excessive collagen degradation is a leading cause of POP. However, the patches currently used in the clinic trigger an unfavorable inflammatory response, which often leads to implantation failure and the inability to simultaneously reverse progressive collagen degradation. Therefore, to overcome the present challenges, a new strategy is applied by introducing puerarin (Pue) into poly(l-lactic acid) (PLLA) using electrospinning technology. PLLA improves the mechanical properties of the patch, while Pue offers intrinsic anti-inflammatory and pro-collagen synthesis effects. The results show that Pue is released from PLLA@Pue in a sustained manner for more than 20 days, with a total release rate exceeding 80%. The PLLA@Pue electrospun patches also show good biocompatibility and low cytotoxicity. The excellent anti-inflammatory and pro-collagen synthesis properties of the PLLA@Pue patch are demonstrated both in vitro in H2O2-stimulated mouse fibroblasts and in vivo in rat abdominal wall muscle defects. Therefore, it is believed that this multifunctional electrospun patch integrating anti-inflammatory and pro-collagen synthesis properties can overcome the limitations of traditional patches and has great prospects for efficient pelvic floor reconstruction.

Design, synthesis and anti-oomycete activity of 2-acyloxyhinokitiol derivatives.

In order to explore novel natural product-based anti-oomycete agent, ten 2-acyloxyhinokitiol derivatives (5a-j) were designed and synthesised, and structurally confirmed by 1H NMR,13C NMR, HRMS, and melting point. The stereochemical configuration of compound 5f was unambiguously confirmed by single-crystal X-ray diffraction. Furthermore, we evaluated the target compounds 5a-j as anti-oomycete activity against a serious agricultural disease of Phytophthora capsici. Among the ten hinokitiol ester derivatives tested, four compounds 5d, 5g, 5h and 5j had anti-oomycete activity higher than the positive control zoxamide (EC50 = 23.59 mg/L), and the EC50 values of 18.90, 20.62, 13.61 and 21.29 mg/L, respectively. Especially compound 5h exhibited the best anti-oomycete activity against P. capsici with EC50 value of 13.61 mg/L. Overall, the anti-oomycete activities of 2-acyloxyhinokitiol derivatives is higher than that of 2-sulfonyloxyhinokitiol derivatives. The results laid a good foundation for the subsequent synthesis of hinokitiol ester derivatives with significant anti-oomycete activity.