Biventricular function after Ebstein's anomaly repair from a single-center echocardiography study.

BACKGROUND: We aimed to examine bi-ventricular remodeling and function following Ebstein's anomaly (EbA) surgical correction using echocardiographic techniques, particularly the relations between the bi-ventricular changes and the EbA types. METHODS: From April 2015 to August 2022, 110 patients with EbA were included in this retrospective study based on the Carpentier classification. Echocardiography assessments during the preoperative, early, and mid-term postoperative periods were performed. RESULTS: The 54 patients with types A and B EbA were included in group 1, whereas the 56 with types C and D were in group 2. Seventy-eight patients underwent surgical correction of EbA. The median age at operation was 8.8 years. During the mid-term follow-up, only 9.1% of the patients had moderate or severe tricuspid regurgitation. Right ventricular (RV) systolic function worsened in group 2 at discharge (fractional area change: 27.6±11.2 versus 35.4±11.5 [baseline], P<0.05; global longitudinal strain: -10.8±4.4 versus -17.9±4.7 [baseline], P=0.0001). RV function slowly recovered at a mean of 12-month follow-up. Regarding left ventricular (LV) and RV systolic function, no statistical difference was found between before and after surgery in group 1. CONCLUSIONS: A high success rate of surgical correction of EbA with an encouraging durability of the valve was noted. Bi-ventricular systolic function was maintained fairly in most patients with types A and B postoperatively. A late increase in RV systolic function after an initial reduction and unchanged LV systolic function were observed in the patients with types C and D postoperatively.

Pharmacokinetic enhancement of oncolytic virus M1 by inhibiting JAK‒STAT pathway.

Oncolytic viruses (OVs), a group of replication-competent viruses that can selectively infect and kill cancer cells while leaving healthy cells intact, are emerging as promising living anticancer agents. Unlike traditional drugs composed of non-replicating compounds or biomolecules, the replicative nature of viruses confer unique pharmacokinetic properties that require further studies. Despite some pharmacokinetics studies of OVs, mechanistic insights into the connection between OV pharmacokinetics and antitumor efficacy remain vague. Here, we characterized the pharmacokinetic profile of oncolytic virus M1 (OVM) in immunocompetent mouse tumor models and identified the JAK‒STAT pathway as a key modulator of OVM pharmacokinetics. By suppressing the JAK‒STAT pathway, early OVM pharmacokinetics are ameliorated, leading to enhanced tumor-specific viral accumulation, increased AUC and Cmax, and improved antitumor efficacy. Rather than compromising antitumor immunity after JAK‒STAT inhibition, the improved pharmacokinetics of OVM promotes T cell recruitment and activation in the tumor microenvironment, providing an optimal opportunity for the therapeutic outcome of immune checkpoint blockade, such as anti-PD-L1. Taken together, this study advances our understanding of the pharmacokinetic-pharmacodynamic relationship in OV therapy.

Effects of cell-free DNA on kidney disease and intervention strategies.

Kidney disease has become a global public health problem. Patients with end-stage kidney disease must rely on dialysis or undergo renal transplantation, placing heavy burdens on their families and society. Therefore, it is important to develop new therapeutic targets and intervention strategies during early stages of chronic kidney disease. The widespread application of liquid biopsy has led to an increasing number of studies concerning the roles of cell-free DNA (cfDNA) in kidney disease. In this review, we summarize relevant studies concerning the roles of cfDNA in kidney disease and describe various strategies for targeted removal of cfDNA, with the goal of establishing novel therapeutic approaches for kidney disease.

Tunable mid-infrared photodetector based on graphene plasmons controlled by ferroelectric polarization for micro-spectrometer.

Surface plasmonic detectors have the potential to be key components of miniaturized chip-scale spectrometers. Graphene plasmons, which are highly confined and gate-tunable, are suitable forin situlight detection. However, the tuning of graphene plasmonic photodetectors typically relies on the complex and high operating voltage based on traditional dielectric gating technique, which hinders the goal of miniaturized and low-power consumption spectrometers. In this work, we report a tunable mid-infrared photodetector by integrating of patterned graphene with non-volatile ferroelectric polarization. The polarized ferroelectric thin film provides an ultra-high surface electric field, allowing the Fermi energy of the graphene to be manipulated to the desired level, thereby exciting the surface plasmon polaritons effect, which is highly dependent on the free carrier density of the material. By exciting intrinsic graphene plasmons, the light transmittance of graphene is greatly enhanced, which improves the photoelectric conversion efficiency of the device. Additionally, the electric field on the surface of graphene enhanced by the graphene plasmons accelerates the carrier transfer efficiency. Therefore, the responsivity of the device is greatly improved. Our simulations show that the detectors have a tunable resonant spectral response of 9-14 µm by reconstructing the ferroelectric domain and exhibit a high responsivity to 5.67×105A W-1 at room temperature. Furthermore, we also demonstrate the conceptual design of photodetector could be used for mid-infrared micro-spectrometer application. .

Association of prenatal multiple metal exposures with child neurodevelopment at 3 years of age: A prospective birth cohort study.

Prenatal exposures to toxic metals and trace elements have been linked to childhood neurodevelopment. However, existing evidence remains inconclusive, and further research is needed to investigate the mixture effects of multiple metal exposures on childhood neurodevelopment. We aimed to examine the associations between prenatal exposure to specific metals and metal mixtures and neurodevelopment in children. In this prospective cohort study, we used the multivariable linear regressions and the robust modified Poisson regressions to explore the associations of prenatal exposure to 25 specific metals with neurodevelopment among children at 3 years of age in 854 mother-child pairs from the Jiangsu Birth Cohort (JBC) Study. The Bayesian kernel machine regression (BKMR) was employed to assess the joint effects of multiple metals on neurodevelopment. Prenatal manganese (Mn) exposure was negatively associated with the risk of non-optimal cognition development of children, while vanadium (V), copper (Cu), zinc (Zn), antimony (Sb), cerium (Ce) and uranium (U) exposures were positively associated with the risk of non-optimal gross motor development. BKMR identified an interaction effect between Sb and Ce on non-optimal gross motor development. Additionally, an element risk score (ERS), representing the mixture effect of multiple metal exposures including V, Cu, Zn, Sb, Ce and U was constructed based on weights from a Poisson regression model. Children with ERS in the highest tertile had higher probability of non-optimal gross motor development (RR = 2.37, 95 % CI: 1.15, 4.86) versus those at the lowest tertile. Notably, Sb [conditional-posterior inclusion probabilities (cPIP) = 0.511] and U (cPIP = 0.386) mainly contributed to the increased risk of non-optimal gross motor development. The findings highlight the importance of paying attention to the joint effects of multiple metals on children's neurodevelopment. The ERS score may serve as an indicator of comprehensive metal exposure risk for children's neurodevelopment.

THBru attenuates diabetic cardiomyopathy by inhibiting RAGE-dependent inflammation.

Diabetic cardiomyopathy (DCM) is a complication of diabetes mellitus characterized by heart failure and cardiac remodeling. Previous studies show that tetrahydroberberrubine (THBru) retrogrades cardiac aging by promoting PHB2-mediated mitochondrial autophagy and prevents peritoneal adhesion by suppressing inflammation. In this study we investigated whether THBru exerted protective effect against DCM in db/db mice and potential mechanisms. Eight-week-old male db/db mice were administered THBru (25, 50 mg·kg-1·d-1, i.g.) for 12 weeks. Cardiac function was assessed using echocardiography. We showed that THBru administration significantly improved both cardiac systolic and diastolic function, as well as attenuated cardiac remodeling in db/db mice. In primary neonatal mouse cardiomyocytes (NMCMs), THBru (20, 40 µM) dose-dependently ameliorated high glucose (HG)-induced cell damage, hypertrophy, inflammatory cytokines release, and reactive oxygen species (ROS) production. Using Autodock, surface plasmon resonance (SPR) and DARTS analyses, we revealed that THBru bound to the domain of the receptor for advanced glycosylation end products (RAGE), subsequently leading to inactivation of the PI3K/AKT/NF-κB pathway. Importantly, overexpression of RAGE in NMCMs reversed HG-induced inactivation of the PI3K/AKT/NF-κB pathway and subsequently counteracted the beneficial effects mediated by THBru. We conclude that THBru acts as an inhibitor of RAGE, leading to inactivation of the PI3K/AKT/NF-κB pathway. This action effectively alleviates the inflammatory responses and oxidative stress in cardiomyocytes, ultimately leading to ameliorated DCM.

Predicting Clinically Significant Prostate Cancer Using Urine Metabolomics via Liquid Chromatography Mass Spectrometry.

PURPOSE: Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles. MATERIALS AND METHODS: Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion. RESULTS: The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88-0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column. CONCLUSIONS: Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.

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

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

Prognostic significance and immune landscape of a cell cycle progression-related risk model in bladder cancer.

BACKGROUND: A greater emphasis has been placed on the part of cell cycle progression (CCP) in cancer in recent years. Nevertheless, the precise connection between CCP-related genes and bladder cancer (BCa) has remained elusive. This study endeavors to establish and validate a reliable risk model incorporating CCP-related factors, aiming to predict both the prognosis and immune landscape of BCa. METHODS: Clinical information and RNA sequencing data were collected from the GEO and TCGA databases. Univariate and multivariate Cox regression analyses were conducted to construct a risk model associated with CCP. The performance of the model was assessed using ROC and Kaplan-Meier survival analyses. Functional enrichment analysis was employed to investigate potential cellular functions and signaling pathways. The immune landscape was characterized using CIBERSORT algorithms. Integration of the risk model with various clinical variables led to the development of a nomogram. RESULTS: To build the risk model, three CCP-related genes (RAD54B, KPNA2, and TPM1) were carefully chosen. ROC and Kaplan-Meier survival analysis confirm that our model has good performance. About immunological infiltration, the high-risk group showed decreased levels of regulatory T cells and dendritic cells coupled with increased levels of activated CD4 + memory T cells, M2 macrophages, and neutrophils. Furthermore, the nomogram showed impressive predictive power for OS at 1, 3, and 5 years. CONCLUSION: This study provides new insights into the association between the CCP-related risk model and the prognosis of BCa, as well as its impact on the immune landscape.

Recent progress in multifunctional, reconfigurable, integrated liquid metal-based stretchable sensors and standalone systems.

Possessing a unique combination of properties that are traditionally contradictory in other natural or synthetical materials, Ga-based liquid metals (LMs) exhibit low mechanical stiffness and flowability like a liquid, with good electrical and thermal conductivity like metal, as well as good biocompatibility and room-temperature phase transformation. These remarkable properties have paved the way for the development of novel reconfigurable or stretchable electronics and devices. Despite these outstanding properties, the easy oxidation, high surface tension, and low rheological viscosity of LMs have presented formidable challenges in high-resolution patterning. To address this challenge, various surface modifications or additives have been employed to tailor the oxidation state, viscosity, and patterning capability of LMs. One effective approach for LM patterning is breaking down LMs into microparticles known as liquid metal particles (LMPs). This facilitates LM patterning using conventional techniques such as stencil, screening, or inkjet printing. Judiciously formulated photo-curable LMP inks or the introduction of an adhesive seed layer combined with a modified lift-off process further provide the micrometer-level LM patterns. Incorporating porous and adhesive substrates in LM-based electronics allows direct interfacing with the skin for robust and long-term monitoring of physiological signals. Combined with self-healing polymers in the form of substrates or composites, LM-based electronics can provide mechanical-robust devices to heal after damage for working in harsh environments. This review provides the latest advances in LM-based composites, fabrication methods, and their novel and unique applications in stretchable or reconfigurable sensors and resulting integrated systems. It is believed that the advancements in LM-based material preparation and high-resolution techniques have opened up opportunities for customized designs of LM-based stretchable sensors, as well as multifunctional, reconfigurable, highly integrated, and even standalone systems.

Na3[Al2B6P4O22(OH)3](H2O)6 and Na3[Al2BP2O11](H2O)0.5: Two Remarkable Complex Aluminum Borophosphates.

Two remarkable aluminum borophosphates (AlBPOs), namely, Na3[Al2B6P4O22(OH)3](H2O)6 (denoted as ABPO1) and Na3[Al2BP2O11](H2O)0.5 (denoted as ABPO2), have been designed and prepared by low-temperature flux syntheses. The exceptional open framework structure of ABPO1 is formed by a unique microanionic network [Al2B6P4O22(OH)3]n3-, which contains three types of 8-, 12-, and 16-membered ring (MR) tunnels. Interestingly, these tunnels are featured by a type of super-nanocage as large as ∼1.753 nm × 1.753 nm × 1.753 nm, which is the first example of AlBPOs containing extra-large cages. Importantly, it was found that Na+ can be partially exchanged by K+, Sr2+, Cd2+, and Ni2+, which means that it is a potential ionic exchanger for removing radionuclides and toxic cations. The structure of ABPO2 features a unique 2D anionic AlBPO layer composed of corner-sharing AlO6 octahedra and AlO4, BO4, and PO4 tetrahedra. To the best of our knowledge, this is the first example of both AlO6 octahedra and AlO4 tetrahedra being contained in the structure. 9-MRs can be observed along the b-axis. Herein, the syntheses and topological structures of ABPO1 and ABPO2 as well as elemental analysis, thermal stability, infrared spectroscopy, UV-vis diffuse reflectance, structural properties, and ionic exchange properties are also discussed.

Pharmacokinetic and oral bioavailability study of schaftoside in rats.

A simple and sensitive LC-tandem mass spectrometry method was established and validated for the determination of schaftoside in rat plasma. After prepared by protein precipitation with acetonitrile, schaftoside and internal standard were separated on a Waters HSS T3 column using acetonitrile containing 0.1% formic acid and 0.1% formic acid in water as the mobile phase by gradient elution. The method showed excellent linearity over the range of 0.5-500 ng/mL with acceptable intra- and inter-day precision, accuracy, matrix effect, and recovery. The stability assay indicated that schaftoside was stable during the sample acquisition, preparation, and storage. The method was applied to a pharmacokinetic study of schaftoside in rats. The result suggested that after intravenous administration at a dose of 1 mg/kg, schaftoside was quickly eliminated from the plasma with an elimination half-life of 0.58 h. After oral administration at doses of 5, 10, and 20 mg/kg, schaftoside was quickly absorbed into the plasma and reached the peak concentration (Cmax) of 45.1-104.99 ng/mL at 0.67-1.17 h. The increase of exposure (area under the curve) was linear with the increase of dose. The oral bioavailability was 0.42%-0.71% in the range of 5-20 mg/kg.

Iridium(III) complexes conjugated with naproxen exhibit potent anti-tumor activities by inducing mitochondrial damage, modulating inflammation, and enhancing immunity.

A series of Ir(III)-naproxen (NPX) conjugates with the molecular formula [Ir(C^N)2bpy(4-CH2ONPX-4'-CH2ONPX)](PF6) (Ir-NPX-1-3) were designed and synthesized, including C^N = 2-phenylpyridine (ppy, Ir-NPX-1), 2-(2-thienyl)pyridine (thpy, Ir-NPX-2) and 2-(2,4-difluorophenyl)pyridine (dfppy, Ir-NPX-3). Cytotoxicity tests showed that Ir-NPX-1-3 exhibited excellent antitumor activity, especially in A549R cells. The cellular uptake experiment showed that the complexes were mainly localized in mitochondria, and induced apoptosis in A549R cells by damaging the structure and function of mitochondria. The main manifestations are a decrease in the mitochondrial membrane potential (MMP), an increase in reactive oxygen species (ROS) levels, and cell cycle arrest. Furthermore, Ir-NPX-1-3 could inhibit the migration and colony formation of cancer cells, demonstrating potential anti-metastatic ability. Finally, the anti-inflammatory and immunological applications of Ir-NPX-1-3 were verified. The downregulation of cyclooxygenase-2 (COX-2) and programmed death-ligand 1 (PD-L1) expression levels and the release of immunogenic cell death (ICD) related signaling molecules such as damage-associated molecular patterns (DAMPs) (cell surface calreticulin (CRT), high mobility group box 1 (HMGB1), and adenosine triphosphate (ATP)) indicate that these Ir(III) -NPX conjugates are novel ICD inducers with synergistic effects in multiple anti-tumor pathways.

Shexiang Baoxin Pill enriches Lactobacillus to regulate purine metabolism in patients with stable coronary artery disease.

BACKGROUND: It has been clinically confirmed that the Shexiang Baoxin Pill (SBP) dramatically reduces the frequency of angina in patients with stable coronary artery disease (SCAD). However, potential therapeutic mechanism of SBP has not been fully explored. PURPOSE: The study explored the therapeutic mechanism of SBP in the treatment of SCAD patients. METHODS: We examined the serum metabolic profiles of patients with SCAD following SBP treatment. A rat model of acute myocardial infarction (AMI) was established, and the potential therapeutic mechanism of SBP was explored using metabolomics, transcriptomics, and 16S rRNA sequencing. RESULTS: SBP decreased inosine production and improved purine metabolic disorders in patients with SCAD and in animal models of AMI. Inosine was implicated as a potential biomarker for SBP efficacy. Furthermore, SBP inhibited the expression of genes involved in purine metabolism, which are closely associated with thrombosis, inflammation, and platelet function. The regulation of purine metabolism by SBP was associated with the enrichment of Lactobacillus. Finally, the effects of SBP on inosine production and vascular function could be transmitted through the transplantation of fecal microbiota. CONCLUSION: Our study reveals a novel mechanism by which SBP regulates purine metabolism by enriching Lactobacillus to exert cardioprotective effects in patients with SCAD. The data also provide previously undocumented evidence indicating that inosine is a potential biomarker for evaluating the efficacy of SBP in the treatment of SCAD.

Assisted reproductive technology and neurodevelopment in children at one year of age: a longitudinal birth cohort study.

BACKGROUND: With remarkable advancements in assisted reproductive technology (ART), the number of ART conceived children continues to increase. Despite increased research investigating the outcomes of ART children, evidence on neurodevelopment remains controversial. OBJECTIVE: The aim of this study was to investigate the association between ART use and neurodevelopment in children at one year of age and to determine whether the characteristics of parental infertility and specific ART procedures affect neurodevelopment in children. STUDY DESIGN: The Jiangsu Birth Cohort enrolled couples who received ART treatment and who conceived spontaneously (2014-2020) in Jiangsu Province, China. In this study, we included 3,531 pregnancies with 3,840 cohort children who completed neurodevelopment assessment at one year of age, including 1,906 infants conceived by ART (including 621 twins). Poisson regressions were fitted to estimate unadjusted and adjusted risk ratios (RRs) and 95% confidence intervals (CIs) for ART use with neurodevelopmental outcomes (cognition, receptive communication, expressive communication, fine motor, and gross motor) in children. RESULTS: Among singletons, ART use was associated with a 24%-34% decrease in the risk for noncompetent development in three domains (cognition, adjusted RR, 0.66; 95% CI, 0.53-0.82; receptive communication, 0.76; 0.64-0.91; expressive communication, 0.69; 0.51-0.93) after adjustment for conventional covariates. However, an inverse association was observed in the gross motor domain, with ART singletons having a greater risk of being noncompetent in gross motor development than their non-ART counterparts (adjusted RR, 1.41; 95% CI, 1.11-1.79). Compared with singletons, twins resulting from ART treatment demonstrated compromised neurodevelopment in several domains. Furthermore, we continued to observe that the transfer of 'poor' quality embryos was associated with greater risks for noncompetent development in receptive communication (adjusted RR, 1.50; 95% CI, 1.05-2.14) and gross motor domains (1.55; 1.02-2.36) among ART singletons. CONCLUSIONS: These results generally provide reassuring evidence among singletons born after ART in the cognition, communication, and fine motor domains, but drawn attention to their gross motor development. The quality of transferred embryos in ART treatment might be associated with offspring neurodevelopment; however, the potential associations warrant further validation in independent studies, and the clinical significance needs careful interpretation.

Transcriptomic and metabolomic correlation analysis: effect of initial SO2 addition on higher alcohol synthesis in Saccharomyces cerevisiae and identification of key regulatory genes.

Introduction: Higher alcohols are volatile compounds produced during alcoholic fermentation that affect the quality and safety of the final product. This study used a correlation analysis of transcriptomics and metabolomics to study the impact of the initial addition of SO2 (30, 60, and 90 mg/L) on the synthesis of higher alcohols in Saccharomyces cerevisiae EC1118a and to identify key genes and metabolic pathways involved in their metabolism. Methods: Transcriptomics and metabolomics correlation analyses were performed and differentially expressed genes (DEGs) and differential metabolites were identified. Single-gene knockouts for targeting genes of important pathways were generated to study the roles of key genes involved in the regulation of higher alcohol production. Results: We found that, as the SO2 concentration increased, the production of total higher alcohols showed an overall trend of first increasing and then decreasing. Multi-omics correlation analysis revealed that the addition of SO2 affected carbon metabolism (ko01200), pyruvate metabolism (ko00620), glycolysis/gluconeogenesis (ko00010), the pentose phosphate pathway (ko00030), and other metabolic pathways, thereby changing the precursor substances. The availability of SO2 indirectly affects the formation of higher alcohols. In addition, excessive SO2 affected the growth of the strain, leading to the emergence of a lag phase. We screened the ten most likely genes and constructed recombinant strains to evaluate the impact of each gene on the formation of higher alcohols. The results showed that ADH4, SER33, and GDH2 are important genes of alcohol metabolism in S. cerevisiae. The isoamyl alcohol content of the EC1118a-ADH4 strain decreased by 21.003%; The isobutanol content of the EC1118a-SER33 strain was reduced by 71.346%; and the 2-phenylethanol content of EC1118a-GDH2 strain was reduced by 25.198%. Conclusion: This study lays a theoretical foundation for investigating the mechanism of initial addition of SO2 in the synthesis of higher alcohols in S. cerevisiae, uncovering DEGs and key metabolic pathways related to the synthesis of higher alcohols, and provides guidance for regulating these mechanisms.

Associations between immune cell phenotypes and lung cancer subtypes: insights from mendelian randomization analysis.

INTRODUCTION: Lung cancer is a common malignant tumor, and different types of immune cells may have different effects on the occurrence and development of lung cancer subtypes, including lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD). However, the causal relationship between immune phenotype and lung cancer is still unclear. METHODS: This study utilized a comprehensive dataset containing 731 immune phenotypes from the European Bioinformatics Institute (EBI) to evaluate the potential causal relationship between immune phenotypes and LUSC and LUAD using the inverse variance weighted (IVW) method in Mendelian randomization (MR). Sensitivity analyses, including MR-Egger intercept, Cochran Q test, and others, were conducted for the robustness of the results. The study results were further validated through meta-analysis using data from the Transdisciplinary Research Into Cancer of the Lung (TRICL) data. Additionally, confounding factors were excluded to ensure the robustness of the findings. RESULTS: Among the final selection of 729 immune cell phenotypes, three immune phenotypes exhibited statistically significant effects with LUSC. CD28 expression on resting CD4 regulatory T cells (OR 1.0980, 95% CI: 1.0627-1.1344, p < 0.0001) and CD45RA + CD28- CD8 + T cell %T cell (OR 1.0011, 95% CI: 1.0007; 1.0015, p < 0.0001) were associated with increased susceptibility to LUSC. Conversely, CCR2 expression on monocytes (OR 0.9399, 95% CI: 0.9177-0.9625, p < 0.0001) was correlated with a decreased risk of LUSC. However, no significant causal relationships were established between any immune cell phenotypes and LUAD. CONCLUSION: This study demonstrates that specific immune cell types are associated with the risk of LUSC but not with LUAD. While these findings are derived solely from European populations, they still provide clues for a deeper understanding of the immunological mechanisms underlying lung cancer and may offer new directions for future therapeutic strategies and preventive measures.

Determining the optimal distal resection margin in rectal cancer patients by imaging of large pathological sections: An experimental study.

OBJECTIVE: To determine the distal resection margin in sphincter-sparing surgery in patients with low rectal cancer based on imaging of large pathological sections. METHODS: Patients who underwent sphincter-sparing surgery for ultralow rectal cancer at Guangxi Medical University Cancer Hospital within the period from January 2016 to March 2022 were tracked and observed. The clinical and pathological data of the patients were collected and analyzed. The EVOS fluorescence automatic cell imaging system was used for imaging large pathological sections. Follow-up patient data were acquired mainly by sending the patients letters and contacting them via phone calls, and during outpatient visits. RESULTS: A total of 46 patients (25 males, 21 females) aged 27 to 86 years participated in the present study. Regarding clinical staging, there were 9, 10, 16, and 10 cases with stages I, II, III, and IV low rectal cancer, respectively. The surgical time was 273.82 ±â€…111.51 minutes, the blood loss was 123.78 ±â€…150.91 mL, the postoperative exhaust time was 3.67 ±â€…1.85 days, and the postoperative discharge time was 10.36 ±â€…5.41 days. There were 8 patients with complications, including 3 cases of pulmonary infection, 2 cases of intestinal obstruction, one case of pleural effusion, and one case of stoma necrosis. The longest and shortest distal resection margins (distances between the cutting edges and the tumor edges) were 3 cm and 1 cm, respectively. The minimum length of the extension areas of the tumor lesions in the 46 images of large pathological sections was 0.1 mm, and the maximum length was 15 mm. Among the tumor lesions, 91.30% (42/46) had an extension area length of ≤5 mm, and 97.83% (45/46) had an extension area length of ≤10 mm. The length of the extension zone was not related to clinical pathological parameters (P > .05). CONCLUSION: In the vast majority of cases, the distal resection margin was at least 1 cm; thus, "No Evidence of Disease" could have been achieved. Additional high-powered randomized trials are needed to confirm the results of the present study.

Innovative technologies for the fabrication of 3D/4D smart hydrogels and its biomedical applications - A comprehensive review.

Repairing and regenerating damaged tissues or organs, and restoring their functioning has been the ultimate aim of medical innovations. 'Reviving healthcare' blends tissue engineering with alternative techniques such as hydrogels, which have emerged as vital tools in modern medicine. Additive manufacturing (AM) is a practical manufacturing revolution that uses building strategies like molding as a viable solution for precise hydrogel manufacturing. Recent advances in this technology have led to the successful manufacturing of hydrogels with enhanced reproducibility, accuracy, precision, and ease of fabrication. Hydrogels continue to metamorphose as the vital compatible bio-ink matrix for AM. AM hydrogels have paved the way for complex 3D/4D hydrogels that can be loaded with drugs or cells. Bio-mimicking 3D cell cultures designed via hydrogel-based AM is a groundbreaking in-vivo assessment tool in biomedical trials. This brief review focuses on preparations and applications of additively manufactured hydrogels in the biomedical spectrum, such as targeted drug delivery, 3D-cell culture, numerous regenerative strategies, biosensing, bioprinting, and cancer therapies. Prevalent AM techniques like extrusion, inkjet, digital light processing, and stereo-lithography have been explored with their setup and methodology to yield functional hydrogels. The perspectives, limitations, and the possible prospects of AM hydrogels have been critically examined in this study.

C-Phycocyanin Attenuates Noise-Induced Cochlear Synaptopathy via the Inhibition of Oxidative Stress and Intercellular Adhesion Molecule-1 in the Cochlea.

The synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) are the most vulnerable structures in the noise-exposed cochlea. Cochlear synaptopathy results from the disruption of these synapses following noise exposure and is considered the main cause of poor speech understanding in noisy environments, even when audiogram results are normal. Cochlear synaptopathy leads to the degeneration of SGNs if damaged IHC-SGN synapses are not promptly recovered. Oxidative stress plays a central role in the pathogenesis of cochlear synaptopathy. C-Phycocyanin (C-PC) has antioxidant and anti-inflammatory activities and is widely utilized in the food and drug industry. However, the effect of the C-PC on noise-induced cochlear damage is unknown. We first investigated the therapeutic effect of C-PC on noise-induced cochlear synaptopathy. In vitro experiments revealed that C-PC reduced the H2O2-induced generation of reactive oxygen species in HEI-OC1 auditory cells. H2O2-induced cytotoxicity in HEI-OC1 cells was reduced with C-PC treatment. After white noise exposure for 3 h at a sound pressure of 118 dB, the guinea pigs intratympanically administered 5 µg/mL C-PC exhibited greater wave I amplitudes in the auditory brainstem response, more IHC synaptic ribbons and more IHC-SGN synapses according to microscopic analysis than the saline-treated guinea pigs. Furthermore, the group treated with C-PC had less intense 4-hydroxynonenal and intercellular adhesion molecule-1 staining in the cochlea compared with the saline group. Our results suggest that C-PC improves cochlear synaptopathy by inhibiting noise-induced oxidative stress and the inflammatory response in the cochlea.