Heatstroke: a multicenter study in Southwestern China.

Background: An increase in Heatstroke cases occurred in southwest China in 2022 due to factors like global warming, abnormal temperature rise, insufficient power supply, and other contributing factors. This resulted in a notable rise in Heatstroke patients experiencing varying degrees of organ dysfunction. This descriptive study aims to analyze the epidemiology and clinical outcomes of Heatstroke patients in the ICU, providing support for standardized diagnosis and treatment, ultimately enhancing the prognosis of Heatstroke. Methods: A retrospective, multicenter, descriptive analysis was conducted on Heatstroke patients admitted to ICUs across 83 hospitals in southwest China. Electronic medical records were utilized for data collection, encompassing various aspects such as epidemiological factors, onset symptoms, complications, laboratory data, concurrent infections, treatments, and patient outcomes. Results: The dataset primarily comprised classic heatstroke, with 477 males (55% of total). The patient population had a median age of 72 years (range: 63-80 years). The most common initial symptoms were fever, mental or behavioral abnormalities, and fainting. ICU treatment involved respiratory support, antibiotics, sedatives, and other interventions. Among the 700 ICU admissions, 213 patients had no infection, while 487 were diagnosed with infection, predominantly lower respiratory tract infection. Patients presenting with neurological symptoms initially (n = 715) exhibited higher ICU mortality risk compared to those without neurological symptoms (n = 104), with an odds ratio of 2.382 (95% CI 1.665, 4.870) (p = 0.017). Conclusion: In 2022, the majority of Heatstroke patients in southwest China experienced classical Heatstroke, with many acquiring infections upon admission to the ICU. Moreover, Heatstroke can result in diverse complications.

Relationship between the intravascular enhancement sign on three-dimensional T1-weighted turbo spin echo and intraluminal thrombus in middle cerebral artery atherosclerosis.

PURPOSE: To investigate the association between the intravascular enhancement sign (IVES) and intraluminal thrombus (ILT) detected by high-resolution magnetic resonance vessel wall imaging (HR-VWI) in patients with middle cerebral artery (MCA) atherosclerosis. METHOD: The data of patients who underwent HR-VWI between May 2021 and May 2023, including clinical information, the number of IVES vessels, stenosis degree, ILT, plaque features on 3D T1-weighted turbo spin echo sequences, and signal intensity ratio (SIR) on 3D time-of-flight magnetic resonance angiography, were retrospectively analyzed. Correlation and logistic regression analyses were performed. RESULTS: A total of 194 MCA plaques were identified in 132 patients (103 [53 %] on the left). Atherosclerosis with, relative to without, ILT was associated with a higher incidence of ischemic events, higher plaque enhancement and stenosis degrees, more vessels with IVES, and lower remodeling ratio, lumen area, wall area, total vessel area, and SIR. Multivariate logistic regression analysis showed significant and independent associations of the number of IVES vessels (OR = 1.089; 95 % CI [1.013-1.170]; P = 0.020) and SIR (OR = 0.007; 95 % CI [0.0004-0.124]; P < 0.001) with ILT. The number of vessels with the IVES (AUC = 0.81, 95 % CI [0.75-0.87]; P < 0.001) and SIR (AUC = 0.88, 95 % CI [0.82-0.94]; P < 0.001) sufficiently diagnosed ILT, and the AUC of the combination of the IVES and SIR was 0.89 (95 % CI [0.84-0.94]; P < 0.001). CONCLUSION: The number of IVES vessels and SIR are independent risk factors for ILT. They may provide new monitoring targets for stroke prevention in patients with atherosclerotic stenosis.

Accuracy of the novel digital non-cross-arch surgical guides with integration of tooth undercut retention and screw-bone support for implant placement in mandibular free-end.

BACKGROUND: Large cross-arch free-end surgical guides can obscure the visual field, compromising surgical accuracy due to insufficient stability at the free-end. This in vitro study aims to evaluate the accuracy of novel digital non-cross-arch surgical guides designed for implant placement at the mandibular free-end, incorporating tooth undercut retention and screw-bone support. MATERIALS AND METHODS: A mandibular dental model lacking left molars was utilized to fabricate unilateral (cross-arch) tooth-supported surgical guides (GT I, n = 20). Subsequently, two additional types of surgical guides were fabricated: GT II (covering two teeth, n = 20) and GT III (covering three teeth, n = 20). These novel surgical guides were designed to utilize the undercut of the supporting teeth for retention and enhance stability with screw-bone support at the guide's free-end. Furthermore, 60 identical guiding blocks were assembled on the three types of surgical guides to facilitate the implants' insertion. On a phantom head, 120 implant replicas were placed at the Federal Dentaire Internationale (FDI) teeth positions #36 and #37 on the dental model, employing a combination of surgical guides and guiding blocks. To assess accuracy, planned and placed implant positions were compared using intraoral optical scanning. Discrepancies in angulation and linear deviations, including the coronal/apical 3D deviations, lateral deviation as well as depth deviation, were measured. Statistical analysis was performed using two-way ANOVA and Bonferroni test (α = 0.05). RESULTS: GT I exhibited significantly largest discrepancies, including angular and linear deviations at the crest and apex at every implant site. Especially in depth, at implant site #36, the mean deviation value of GT I (0.27 ± 0.13 mm) was twice as large as GT III (0.13 ± 0.07 mm), and almost twice as large as GT II (0.14 ± 0.08 mm). However, at implant site #37, this deviation increased to almost a five-fold relationship between GT I (0.63 ± 0.12 mm) and II (0.14 ± 0.09 mm), as well as between GT I and III (0.13 ± 0.09 mm). No significant discrepancies existed between the novel surgical guides at either implant site #36 or #37. CONCLUSION: This study provides a practical protocol for enhancing accuracy of implant placement and reducing the size of free-end surgical guides used at mandibular molar sites.

Psychosocial adjustment changes and related factors in young and middle-aged patients with first-episode acute myocardial infarction: a longitudinal study.

AIMS: This study aimed to explore the change trend and group heterogeneity of psychosocial adjustment level and to determine its influencing factors among young and middle-aged patients with first-episode acute myocardial infarction (AMI). METHODS AND RESULTS: The Psychosocial Adjustment Scale of Illness was used to assess the psychosocial adjustment level of the patients at 1, 3, and 6 months after discharge, respectively. Data were analyzed using Pearson correlation analysis, generalized estimating equations, and growth mixed models. A total of 233 patients were included, and their psychosocial adjustment scores at the three-time points were 57.18 ± 15.50, 36.17 ± 15.02, and 24.22 ± 12.98, respectively. The trajectories of changes in patients' psychosocial adjustment levels were divided into three latent categories: moderate adjustment improvement group (72.5%), low adjustment improvement group (16.3%), and persistent maladjustment group (11.2%). Among them, predictors of the persistent maladjustment group included no spouse, low monthly family income per capita, normal body mass index, never smoking, never exercising, combined with hyperlipidemia, low social support, submission coping, and high perceived stress. CONCLUSIONS: The psychosocial adjustment level of young and middle-aged patients with first-episode AMI showed an upward trend within 6 months after discharge, and there was group heterogeneity in the change trajectory of psychosocial adjustment level. It is suggested that a multi-center, large-sample longitudinal study should be carried out in the future, and the time of follow-up investigation should be extended to further clarify the change trajectory and influencing factors of psychosocial adjustment of patients with different subtypes, to provide the theoretical basis for formulating targeted intervention programs.

Chemical diversity, traditional uses, and bioactivities of Rosa roxburghii Tratt: A comprehensive review.

Rosa roxburghii Tratt (RRT), known as chestnut rose, has been a subject of growing interest because of its diverse chemical composition and wide range of traditional uses. This comprehensive review aimed to thoroughly examine RRT, including its traditional applications, chemical diversity, and various bioactivities. The chemical profile of this plant is characterized by the presence of essential nutrients such as vitamin C (ascorbic acid), flavonoids, triterpenes, organic acids, tannins, phenolic compounds, polysaccharides, carotenoids, triterpenoids, volatile compounds, amino acids, and essential oils. These constituents contribute to the medicinal and nutritional value. Additionally, we explore the multifaceted bioactivities of RRT, including its potential as an anticancer agent, antioxidant, antiaging agent, antiatherogenic agent, hypoglycemic agent, immunoregulatory modulator, radioprotective agent, antimutagenic agent, digestive system regulator, anti-inflammatory agent, cardioprotective agent, and antibacterial agent, and its intriguing role in modulating the gut microbiota. Furthermore, we discuss the geographical distribution and genetic diversity of this plant species and shed light on its ecological significance. This comprehensive review provides a holistic understanding of RRT, bridges traditional knowledge with contemporary scientific research, and highlights its potential applications in medicine, nutrition, and pharmacology.

Successful ECMO treatment in patients with cerebral hemorrhage and PROC gene mutation associated with VTE: a case report.

In this report, we report a case of a middle-aged male, admitted to the ICU with cerebral hemorrhage resulting from a severe high-altitude fall. The patient encountered significant challenges in oxygenation index correction, attributed to extensive embolism in both the primary and branch pulmonary arteries. Consequently, the patient underwent an immediate initiation of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy, persisting for 20 days. During this treatment period, a mutation in the protein C (PROC) gene was identified. The medical team meticulously navigated the delicate balance between anticoagulation and bleeding risks. Eventually, the patient was successfully weaned off VA-ECMO and subsequently discharged. This report aims to delve into the etiology and therapeutic approaches of this uncommon case, with the intention of offering insightful reference for managing similar clinical scenarios in the future.

Quercetin of huoxuehuayu tongluo decoction and azithromycin combination therapy effectively improves rat tubal factor infertility by inhibiting inflammation.

Objectives: Tubal factor infertility (TFI) is common female infertility responsible for a large portion of female factor infertility. This study reveals the effect of the quercetin of Huoxuehuayu Tongluo Decoction with azithromycin on the pregnancy rate and inflammation of TFI female rats. Materials and Methods: Female Sprague Dawley rats were constructed into the TFI model and treated with quercetin, Huoxuehuayu Tongluo Decoction, and combination therapy (quercetin and azithromycin). Pregnancy rate and litter size were measured. Network pharmacology was applied to analyze the interaction between Huoxuehuayu Tongluo Decoction and TFI. The combination of quercetin and IL-6 was analyzed by molecular docking. HE staining and electron microscopy were used to observe the histopathology and ultrastructure of fallopian tube tissues. The TNF-α, IL-1ß, IL-6, IL-8, and MPO levels were detected by ELISA. The activation of JAK/STAT, MAPK, and NF-κB p65 pathways was detected by western blot or immunohistochemistry. Results: Quercetin was the main active component of Huoxuehuayu Tongluo Decoction, and could bind to IL-6 in TFI. Target genes were enriched in the IL-17 signaling pathway, JAK-STAT signaling pathway, inflammatory disease, etc. Under the quercetin and azithromycin combination therapy, both rat pregnancy rates and litter sizes increased significantly. quercetin and azithromycin alleviated the symptoms of hydrosalpinx and inflammatory damage in fallopian tube tissues. The phosphorylation of JAK/STAT and MAPK pathways and NF-κB p65 translocation to the nucleus were significantly inhibited by the quercetin and azithromycin therapy. Conclusion: Quercetin and azithromycin combination therapy inhibited inflammation and phosphorylation of JAK/STAT and MAPK pathways to improve TFI inflammation and pregnancy function.

The influence of different load distribution considering geometric error on the fatigue life of ball screw.

The ball screw pair is a precision drive component that converts rotary motion into linear motion. In practical applications, because the feed system usually has rotational torque and geometric errors, it may increase the contact load of the ball screw pair and reduce the fatigue life. In order to study the influence of different loads and geometric errors on the maximum contact load and fatigue life of ball screw pairs, the following research work was carried out. Firstly, based on the composite load and rotational torque, the ball load distribution model is established, and the accuracy of the model is verified by finite element modeling analysis. Then, the influence of different composite loads, rotation times and geometric errors (including ball size error, lead error and raceway tooth profile error) on the ball load distribution is analyzed. Finally, the influence of compound load, rotating torque and geometric error on the fatigue life of ball screw pairs is studied. The results show that the rotational torque and lead error have a great influence on the load distribution and fatigue life of the ball, and the influence of lead error on load distribution is greater than that of dimension error and tooth profile error. The fatigue life of the ball screw pair with non-uniform load distribution is shorter than that of the ball screw pair with uniform load distribution.

The Therapeutic Effectiveness of Laparoscopic Sleeve Gastrectomy Among Individuals with Low BMI Obesity (30-35 Kg/m2) and the Relationship of BMI to Weight Loss.

Purpose: Investigating the therapeutic efficacy of Laparoscopic Sleeve Gastrectomy (LSG) in low BMI (30-35 kg/m2) patients with obesity, and exploring the correlation between patients' preoperative BMI and postoperative weight loss. Methods: Comparing the weight loss, remission of comorbidities, occurrence of complications, and quality of life among the different BMI patients who underwent LSG. Analyzing the relationship between BMI and percentage of excess weight loss (%EWL) by using Spearman correlation analysis and linear regression analysis. Results: The %EWL at 12 months after the surgical procedure was (104.26±16.41)%, (90.36±9.98)%, and (78.30±14.64)% for patients with Class I, II, and III obesity, respectively, P<0.05. Spearman correlation coefficients between %EWL and BMI at 1, 3, 6, and 12 months after surgery were R=-0.334 (P<0.001), R=-0.389 (P<0.001), and R=-0.442 (P<0.001), R=-0.641 (P<0.001), respectively. The remission of hypertension, diabetes and dyslipidaemia did not differ significantly between groups (P>0.05). Conclusion: Individuals with obesity for varying BMI can experience favorable outcomes following LSG surgery. It is advisable to consider LSG treatment for patients with Class I obesity.

First Report of Brown Leaf Rot Disease on Dendrobium nobile Caused by Xylaria flabelliformis in Guizhou Province, China.

Dendrobium nobile is the largest species of the Orchidaceae family and produces dendrobine, a compound with medicinal properties (Sarsaiya et al., 2020a; Sarsaiya et al., 2024; Qian et al., 2024). The accumulation of dendrobine in D. nobile is regulated by various pathogenic fungi, which directly and indirectly influence dendrobine biosynthesis (Sarsaiya et al., 2019a; Sarsaiya et al., 2019b). In a field planted with D. nobile in Guizhou Province, China, small lesions were initially observed on the upper part of the leaves from May to June 2019, which later developed into larger brown necrotic leaf lesions. Over time, these lesions greatly impacted the medicinal value (dendrobine) and productivity of the plant. A pure culture of Xylaria flabelliformis from infected wild D. nobile leaves was recovered and subsequently cultured on potato dextrose agar (PDA) at 25 °C for 5 days. Xylaria flabelliformis grew slowly and was composed of white mycelia. Colonies were initially white, with a regular margin, and formed stromata that consisted of mycelia sterilia without ascospores. We identified the strain as Xylaria flabelliformis based on its morphological characteristics (Liu et al., 2007) and by sequencing elongation factor-1α (EF-1α). The length of the DNA sequence of EF-1α that was used for the analysis of Xylaria flabelliformis was 1188 bp. BLASTx (nucleotide 6-frame translation-protein) analysis using the National Center for Biotechnology Information database showed that the obtained protein sequence (BLASTx protein accession no.: UTS95822.1, BLASTn nucleotide sequence accession no.: MW508334.1) had the highest similarity (98.21%) with the X. flabelliformis hypothetical protein (TRX95197.1) based on a thorough phylogenetic comparison with other Xylaria species. Healthy D. nobile seedlings were planted in pots and sterilized. The terminal leaves were excised from all pre-sterilised D. nobile seedlings and inoculated with Xylaria flabelliformis mycelial plugs, whereas sterile PDA plugs and moist cotton plugs were used as controls. All seedlings were maintained under optimum temperature and humidity conditions (25 °C and 80%, respectively) for seven days for observation and analysis. All experiments were performed in triplicate. After the incubation period, brown leaf rot lesions were observed for the first time on the inoculated D. nobile leaves, but no symptoms were observed on the leaves of the two control groups (sterile PDA plugs and moist cotton plugs). To complete Koch's postulates, Xylaria flabelliformis was re-isolated and identified from all diseased tissues by DNA sequencing of the EF-1α. It was determined for the first time that Xylaria flabelliformis can cause brown leaf lesions in D. nobile. Moreover, the pathogenicity of Xylaria flabelliformis in D. nobile has not been previously reported (Mead et al., 2019; Meng et al., 2019; Sarsaiya et al., 2019a; Sarsaiya et al., 2020b; Chen et al., 2023; Rinchen, 2023; Cao et al., 2024). To the best of our knowledge, this is the first report of BLRS lesions in D. nobile leaves caused by Xylaria flabelliformis in Guizhou Province, China. Identification of Xylaria flabelliformis as a pathogen of D. nobile is crucial for advancing effective management and control practices against brown leaf rot disease. This discovery provides valuable insights into the development of targeted strategies to mitigate the impact of Xylaria flabelliformis on D. nobile, safeguard medicinal properties such as dendrobine, and enhance overall productivity.

Cellulose nanocrystals intercalated clay biocomposite for rapid Cr(VI) removal.

The application of bentonite (Bt) as an adsorbent for heavy metals has been limited due to its hydrophobicity and insufficient surface area. Herein, we present cellulose nanocrystal (CNC) modified Bt composite (CNC@Bt) with enhanced efficiency for Cr(VI) removal. CNC@Bt exhibited an increased specific surface area and a porous structure, while maintaining the original crystal structure of Bt. This was achieved through a synergistic function of ion exchange, hydrogen bonding, electrostatic interactions, and steric hindrance. The adsorption of Cr(VI) by CNC@Bt followed the pseudo-second-order kinetic and Langmuir isotherm adsorption model. Moreover, the process was endothermic and spontaneous. At an initial Cr(VI) concentration of 20 mg/L and pH = 4.0, 10 g/L CNC@Bt achieved a removal rate of 92.7%, and the adsorption capacity was 1.85 mg/g, significantly higher than bare Bt (37.9% and 0.76 mg/g). The removal efficiency remained consistently above 80% over a wide pH range, indicating the potential practical applicability of CNC@Bt. With its fast adsorption rate, pH adaptability, and stable performance, CNC@Bt presents promising prospects for the rapid treatment of Cr-contaminated wastewater.

Inhibition of mitochondrial ROS-mediated necroptosis by Dendrobium nobile Lindl. alkaloids in carbon tetrachloride induced acute liver injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium nobile Lindl. (DNL) is a well-known traditional Chinese medicine that has been recorded in the Chinese Pharmacopoeia (2020 edition). The previous data showed that Dendrobium nobile Lindl. alkaloids (DNLA) protect against CCl4-induced liver damage via oxidative stress reduction and mitochondrial function improvement, yet the exact regulatory signaling pathways remain undefined. AIM OF THE STUDY: The aim of the present study was to investigate the role of necroptosis in the mode of CCl4-induced liver injury and determine whether DNLA protects against CCl4-induced acute liver injury (ALI) by inhibiting mitochondrial ROS (mtROS)-mediated necroptosis. MATERIALS AND METHODS: DNLA was extracted from DNL, and the content was determined using liquid chromatograph mass spectrometer (LC-MS). In vivo experiments were conducted in C57BL/6J mice. Animals were administrated with DNLA (20 mg/kg/day, ig) for 7 days, and then challenged with CCl4 (20 µL/kg, ip). CCl4-induced liver injury in mice was evaluated through the assessment of biochemical indicators in mouse serum and histopathological examination of hepatic tissue using hematoxylin and eosin (H&E) staining. The protein and gene expressions were determined with western blotting and quantitative real-time PCR (RT-qPCR). Reactive oxygen species (ROS) production was detected using the fluorescent probe DCFH-DA, and mitochondrial membrane potential was evaluated using a fluorescent probe JC-1. The mtROS level was assessed using a fluorescence probe MitoSOX. RESULTS: DNLA lessened CCl4-induced liver injury, evident by reduced AST and ALT levels and improved liver pathology. DNLA suppressed necroptosis by decreasing RIPK1, RIPK3, and MLKL phosphorylation, concurrently enhancing mitochondrial function. It also broke the positive feedback loop between mtROS and RIPK1/RIPK3/MLKL activation. Similar findings were observed with resveratrol and mitochondrial SOD2 overexpression, both mitigating mtROS and necroptosis. Further mechanistic studies found that DNLA inhibited the oxidation of RIPK1 and reduced its phosphorylation level, whereby lowering the phosphorylation of RIPK3 and MLKL, blocking necroptosis, and alleviating liver injury. CONCLUSIONS: This study demonstrates that DNLA inhibits the necroptosis signaling pathway by reducing mtROS mediated oxidation of RIPK1, thereby reducing the phosphorylation of RIPK1, RIPK3, and MLKL, and protecting against liver injury.

Clinical knowledge-guided deep reinforcement learning for sepsis antibiotic dosing recommendations.

Sepsis is the third leading cause of death worldwide. Antibiotics are an important component in the treatment of sepsis. The use of antibiotics is currently facing the challenge of increasing antibiotic resistance (Evans et al., 2021). Sepsis medication prediction can be modeled as a Markov decision process, but existing methods fail to integrate with medical knowledge, making the decision process potentially deviate from medical common sense and leading to underperformance. (Wang et al., 2021). In this paper, we use Deep Q-Network (DQN) to construct a Sepsis Anti-infection DQN (SAI-DQN) model to address the challenge of determining the optimal combination and duration of antibiotics in sepsis treatment. By setting sepsis clinical knowledge as reward functions to guide DQN complying with medical guidelines, we formed personalized treatment recommendations for antibiotic combinations. The results showed that our model had a higher average value for decision-making than clinical decisions. For the test set of patients, our model predicts that 79.07% of patients will achieve a favorable prognosis with the recommended combination of antibiotics. By statistically analyzing decision trajectories and drug action selection, our model was able to provide reasonable medication recommendations that comply with clinical practices. Our model was able to improve patient outcomes by recommending appropriate antibiotic combinations in line with certain clinical knowledge.

Near-infrared dual-response fluorescent probe for detection of N2H4 and intracellular viscosity changes in biological samples and various water samples.

N2H4 is a common raw material used in the production of pesticides and has good water solubility, so it may contaminate water sources and eventually enter living organisms, causing serious health problems. Viscosity is an important indicator of the cellular microenvironment and an early warning signal for many diseases. The high reactivity of hydrazine depletes glutathione (GSH) in hepatocytes, causing oxidative stress ultimately leading to significant changes in intracellular viscosity and even death. Therefore, it is particularly important to develop an effective method to detect N2H4 and viscosity in environmental and biological systems. On this basis, we developed two fluorescent probes, BDD and BHD, based on xanthene and 2-benzothiazole acetonitrile. The experimental results show that BHD and BDD have good imaging capabilities for N2H4 in cells, zebrafish and Arabidopsis. BHD and BDD also showed sensitive detection and fluorescence enhancement in the near-infrared region when the intracellular viscosity was changed. Notably, the probe BDD has also successfully imaged N2H4 in a variety of real water samples.

Roxadustat Versus Erythropoietin: The Comparison of Efficacy in Reversing Ventricular Remodeling in Dialysis Patients with Anaemia.

Background: Renal anaemia and left ventricular hypertrophy are the main complications of chronic kidney disease and are shared among dialysis patients. This retrospective study aimed to compare the efficacies of the hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat and recombinant human erythropoietin in reversing ventricular remodeling in dialysis patients with renal anaemia. Methods: A total of 204 participants underwent baseline examinations, including echocardiograms and laboratory tests, before being administered either treatment for at least 24 weeks from January 2018 to October 2021, after which follow-up examinations were conducted at 6 months. Propensity score matching based on key variables included age, gender, cardiovascular diseases, cardiovascular medications, dialysis course and the vascular access at baseline was performed to include populations with similar characteristics between groups. Results: In total, 136 patients were included with roxadustat or recombinant human erythropoietin. The left ventricular mass index after treatment with roxadustat and recombinant human erythropoietin both significantly decreased after 6 months, but there was no significant difference in the change in left ventricular mass index between the two groups. In addition, the left ventricular end-diastolic diameters and left ventricular wall thickness, systolic blood pressure, and diastolic blood pressure significantly decreased in the roxadustat group. Roxadustat and recombinant human erythropoietin also increased haemoglobin significantly, but there was no significant difference in the change in haemoglobin between the two groups. The results of multiple linear regression showed that the change in haemoglobin was independent factor affecting the improvement of left ventricular mass index. Conclusions: The increase of haemoglobin was associated with improving left ventricular hypertrophy in dialysis patients. However, the beneficial effects between roxadustat and recombinant human erythropoietin on left ventricular mass index did not show clear superiority or inferiority in six months.

A fluorescent probe for detecting H2O2 and delivering H2S in lysosomes and its application in maintaining the redox environments.

Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) that can be used as a marker for the occurrence of oxidative stress in the organism. Lysosomes serve as intracellular digestive sites, and when the concentration of H2O2 in them is abnormal, lysosomal function is often impaired, leading to the development of diseases. Hydrogen sulfide (H2S) acts as a gaseous signaling molecule that scavenges H2O2 from cells and tissues, thereby maintaining the redox environment of the body. However, most of the reported hydrogen peroxide fluorescent probes so far can only detect H2O2, but cannot maintain the intracellular redox environment. In this paper, an H2O2 fluorescent probe LN-HOD with lysosomal targeting properties was designed and synthesized by combining the H2O2 recognition site with a naphthylamine fluorophore via a thiocarbamate moiety. The probe has the advantages of large Stokes shift (110 nm), high sensitivity and good H2S release capability. The probe LN-HOD can be used to detect H2O2 in cells, zebrafish and plant roots. In addition, LN-HOD detects changes in the concentration of H2O2 in plant roots when Arabidopsis is stressed by cadmium ion (Cd2+). And through its ability to release H2S, it can help to remove excess H2O2 and maintain the redox environment in cells, zebrafish and plant roots. The present work provides new ideas for the detection and assisted removal of H2O2, which contributes to the in-depth study of the cellular microenvironment in organisms.

Multivalent Aptamer-Based Lysosome-Targeting Chimeras (LYTACs) Platform for Mono- or Dual-Targeted Proteins Degradation on Cell Surface.

Selective protein degradation platforms have opened novel avenues in therapeutic development and biological inquiry. Antibody-based lysosome-targeting chimeras (LYTACs) have emerged as a promising technology that extends the scope of targeted protein degradation to extracellular targets. Aptamers offer an advantageous alternative owing to their potential for modification and manipulation toward a multivalent state. In this study, a chemically engineered platform of multivalent aptamer-based LYTACs (AptLYTACs) is established for the targeted degradation of either single or dual protein targets. Leveraging the biotin-streptavidin system as a molecular scaffold, this investigation reveals that trivalently mono-targeted AptLYTACs demonstrate optimum efficiency in degrading membrane proteins. The development of this multivalent AptLYTACs platform provides a principle of concept for mono-/dual-targets degradation, expanding the possibilities of targeted protein degradation.

Development of an indirect ELISA against Orf virus using two recombinant antigens, partial B2L and F1L.

Orf is a highly contagious viral disease affecting goats and sheep. It is caused by Orf virus (ORFV) and has caused severe economic losses to the global goat industry, including in China. In this study, an indirect ELISA method for recombinant proteins based on truncated dominant antigenic epitopes of B2L and F1L genes of ORFV was established. A series of conditions and its performance were comprehensively evaluated. The optimized ELISA reaction conditions were: the optimal coating amount of antigen was 0.25 µg/mL, 5% skim milk powder was closed for 1 h, the optimal dilution of serum was 1:200, the optimal incubation time of the rabbit anti-goat IgG was 1:8000, the optimal color development time of TMB was 15 mins, and the threshold value of negative-positive was 0.358. The method specifically detects anti-ORFV antibodies and does not cross-react with positive sera for other common goat pathogenic bacteria antiserum. ORFV-positive sera were still positive after 1:512 dilution, with intra-batch coefficient of variation (CV) between 7.1% and 9.5% and inter-batch CV between 5.0% and 7.6%; 51% (92/180) of immunized goat serum samples were tested positive and 14.44% (14/63) of non-immunized goat serum samples were positive. The results show that the indirect ELISA antibody assay established in this study has good specificity, sensitivity and reproducibility, and provides a technical tool for clinical ORFV serum antibody detection and epidemiological investigation.