The High Estradiol Environment after IVF Causes the Increased Risk of Glucose Metabolic Dysfunction in Offspring.

CONTEXT: Assisted reproductive technology (ART) is associated with increased metabolic risks in offspring. The effect of high maternal estradiol (E2) levels during early pregnancy on the glucose metabolism of offspring remains unclear. OBJECTIVE: To evaluate glucose metabolism in in vitro fertilization (IVF)-conceived children and assess whether high E2 exposure during early pregnancy is associated with metabolic alterations. DESIGN/SETTING/PARTICIPANTS: This retrospective analysis included 500 singletons aged 3-10 years born after fresh embryo transfer (ET) (n=200), frozen ET (n=100), and natural conception (NC) (n=200) from a university hospital. METHODS: Children underwent anthropometric measurements and examinations for fasting glucose, insulin, and lipid levels. A mouse model of high E2 exposure during early pregnancy was established to study glucose and insulin tolerance, and insulin secretion. RESULTS: Compared with NC, children born after fresh ET showed higher fasting glucose/insulin levels, increased insulin resistance, and higher incidence of impaired fasting glucose, which might be associated with a higher maternal E2 levels. Frozen ET showed intermediate results. In mice, offspring exposed to high E2 levels during gestation exhibited impaired glucose/insulin tolerance and defects in insulin secretion. CONCLUSION: High maternal E2 levels in early pregnancy are associated with altered glucose metabolism and increased metabolic risks in IVF-conceived children. Further studies are needed to elucidate the underlying mechanisms.

Identification of endocrine-disrupting chemicals targeting key OP-associated genes via bioinformatics and machine learning.

Osteoporosis (OP), a metabolic disorder predominantly impacting postmenopausal women, has seen considerable progress in diagnosis and treatment over the past few decades. However, the intricate interplay between genetic factors and endocrine disruptors (EDCs) in the pathogenesis of OP remains inadequately elucidated. The objective of this research is to examine the environmental pollutants and their regulatory mechanisms that could potentially influence the pathogenesis of OP, in order to establish a theoretical foundation for the targeted prevention and medical management of individuals with OP. Utilizing CTD and GEO datasets, network toxicology and bioinformatics analyses were conducted to identify target genes from a pool of 98 co-associated genes. Subsequently, a novel prediction model was developed employing a multiple machine learning algorithm. The efficacy of the model was validated based on the area under the receiver operating characteristic curve. Finally, real-time quantitative polymerase chain reaction (qRT-PCR) was used to confirm the expression levels of key genes in clinical samples. We have identified significant genes (FOXO3 and LUM) associated with OP and conducted Gene Ontology, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, immune infiltration analysis, and molecular docking analysis. Through the analysis of these key genes, we have identified 13 EDCs that have the potential to impact OP. Several endocrine disruptors, such as Dexamethasone, Perfluorononanoic acid, genistein, cadmium, and bisphenol A, have been identified as notable environmental pollutants that impact the OP. Molecular docking analysis revealed significant binding affinity of major EDCs to the post-translational protein structures of key genes. This study demonstrates that EDCs, including dexamethasone, perfluorononanoic acid, genistein, cadmium, and bisphenol A, can be identified as important environmental pollutants affecting OP, and that FOXO3 and LUM have the potential to be diagnostic markers for OP. These results elucidate a novel association between EDCs regulated by key genes and the onset of OP.

Retraction: Effects of thermal aging atmospheres on oxidation activity, element composition and microstructure of diesel soot particles.

[This retracts the article DOI: 10.1039/D3RA05340G.].

Unraveling the roles and mechanisms of mitochondrial translation in normal and malignant hematopoiesis.

Due to spatial and genomic independence, mitochondria possess a translational mechanism distinct from that of cytoplasmic translation. Several regulators participate in the modulation of mitochondrial translation. Mitochondrial translation is coordinated with cytoplasmic translation through stress responses. Importantly, the inhibition of mitochondrial translation leads to the inhibition of cytoplasmic translation and metabolic disruption. Therefore, defects in mitochondrial translation are closely related to the functions of hematopoietic cells and various immune cells. Finally, the inhibition of mitochondrial translation is a potential therapeutic target for treating multiple hematologic malignancies. Collectively, more in-depth insights into mitochondrial translation not only facilitate our understanding of its functions in hematopoiesis, but also provide a basis for the discovery of new treatments for hematological malignancies and the modulation of immune cell function.

Analysis and insights of cardiac amyloidosis: novel perception of rare diseases in cardiology.

BACKGROUND: Amyloidosis is a rare systemic disease, while cardiac amyloidosis (CA) is nothing more than a chronic disease that causes fatal damage to the structure and function of the heart. The pathogenesis of CA is elusive, the clinical manifestations are diverse and lack of specificity, and the treatment and prognosis of different subtypes vary widely. It is of great practical significance to deepen the understanding of CA. OBJECTIVE AND METHODS: The clinical data of 39 patients with CA admitted to the First Affiliated Hospital of Gannan Medical University and Fujian Medical University Union Hospital from January 1, 2018 to March 1, 2024 were collected and retrospectively studied, and the clinical features, diagnosis, differentiation, treatment effects and prognosis of CA patients were analyzed. The Kaplan-Meier method was used for survival analysis. Meanwhile, the latest literature from PubMed was retrieved to systematically discuss the research progress in the diagnosis and treatment of CA. This paper is expected to provide novel and valuable references for the clinical and basic research of CA. RESULTS: A total of 39 patients with CA were included in this study, including 23 males (58.97%) and 16 females (41.03%). The average age at diagnosis was 60.51±10.28 years old. In this study, 24 patients (61.54%) had anemia of different degrees, 19 patients (48.72%) were accompanied by abnormal elevation of cardiac troponin T (cTnT), and all patients (100%) had abnormal elevation of N-terminal pro-brain natriuretic peptide (NT-proBNP), and 28 patients (71.79%) had renal impairment. Typical electrocardiogram (ECG) findings in CA patients in this study show low voltage in limb leads, various types of atrioventricular block, various types of tachycardia, atrial fibrillation and poor R-wave progression. The representative results of ultrasonic cardiogram (UCG) showed: 1. Atrium were enlarged, and ventricular wall motion was weakened. 2. Septum and posterior walls of the ventricle were symmetrically thickened, and the myocardium showed speckled strong echo. 3. Mitral regurgitation (moderate to severe) and tricuspid regurgitation. 4. Widening of the pulmonary artery and pulmonary hypertension. Typical results of cardiac magnetic resonance imaging (MRI) of CA patients in this study showed that delayed gadolinium enhancement of the ventricular wall, with ventricular wall thickening to varying degrees and ventricle or atrium enlargement. The pathological manifestations of CA patients in this study were mostly Congo red staining (+) and deposition of eosinophilic amyloid in the affected organs or tissues. All CA patients included in this study received standardized treatment, the median follow-up time was 29.5 (range, 6.5-71) months, and at the latest follow-up, only 12 cases of 39 patients with CA were still alive, and 27 patients died in our study, all of which were due to uncontrollable progression of the disease and failed treatment. Our study showed that there is no statistical significance in the different age groups of the CA patients (P>0.05), while it was surprising that male CA patients had significantly worse overall survival (OS) than female patients. Correspondingly, patients who received chemotherapy and were accompanied with renal impairment had a worse prognosis than those who did not receive chemotherapy and had normal renal function (all P<0.05). CONCLUSION: CA is a rare disease caused by systemic amyloidosis, the pivotal points of CA diagnosis and treatment as well as the premise for improving the long-term prognosis of CA patients are clear diagnosis and accurate typing. The treatment of CA also requires targeted individual treatment according to the subtype and etiology of CA patients, so as to maximize the prognosis of CA patients.

Outcome of Pneumocystis Jirovecii pneumonia (PcP) in post-CAR-T patients with hematological malignancies.

BACKGROUND: Pneumocystis jirovecii pneumonia (PcP) is an opportunistic infection associated with immunocompromised patients. The development of novel immunotherapies has promoted the incidence of PcP. This study describes the clinical course and outcome of PcP in chimeric antigen receptor (CAR) T cell recipients with hematological malignancies. METHODS: This is a retrospective case series of CAR-T recipients diagnosed with PcP in our center. The cases were all confirmed by metagenomic next-generation sequencing of clinical samples. The demographic, clinical, and outcome data were retrieved from the patients' medical charts and electronic medical record system. RESULTS: In total, 8 cases of PcP were identified. The underlying malignancies included T-acute lymphoblastic leukemia (ALL) (n = 1), diffuse large B cell lymphoma (DLBCL) (n = 4), and B-ALL (n = 3). One patient received short-term sulfamethoxazole-trimethoprim (SMZ-TMP) while the others had no prophylaxis. Four patients had neutropenia/lymphopenia at the diagnosis of PcP, and two patients had immunosuppressants within one month before PcP manifestation. The median time from CAR-T infusion to PcP diagnosis was 98.5 days (range 52-251). Seven patients recovered from PcP after proper management while one died of septic shock. CONCLUSION: PcP can occur after different CAR-T product, and the long-term depletion of immune cells seems to be related to PcP. SMZ-TMP is effective in this setting. More real-world experience of CAR-T therapy is required to assess the incidence and outcome of PcP in this population.

Association study reveals a susceptibility locus with male pattern baldness in the Han Chinese population.

Introduction: Male pattern baldness (MPB), also known as androgenetic alopecia, represents the most prevalent form of progressive hair loss in humans. It is characterized by a distinctive pattern of hair loss progression from the scalp; however, its underlying mechanism remains elusive and is influenced by hereditary, immune, and environmental factors. Genome-wide association studies (GWASs) have uncovered numerous risk genes/loci among European individuals with MPB. However, the validation of these susceptibility genes/loci within Han Chinese men remains largely unexplored. The aim of this study was to investigate whether the 71 susceptibility loci identified in a recent GWAS among European men also confer risk for MPB in Chinese men. Methods: Forty-seven single nucleotide polymorphisms (SNPs) previously reported in GWASs of MPB were selected and genotyped in independent individuals comprising 499 Han Chinese cases and 1,489 controls using the Sequenom MassArray system. After stringent quality control measures, 25 SNPs were subjected to statistical analyses. Cochran-Armitage trend test was used to evaluate the association between SNPs and disease susceptibility. To address multiple tests, Bonferroni correction was conducted, setting the threshold for statistical significance at a p-value <2 × 10-3 (0.05/25). Results: The rs13405699 SNP located at 2q31.1 exhibited a significant association with MPB in Han Chinese men (p = 4.84 × 10-5, OR = 1.37, 95% CI: 1.18-1.59). Moreover, the difference in rs13405699 genotype distribution between MPB cases and controls was statistically significant (p = 7.00 × 10-5). Genotype-based association analysis suggested that the recessive model provided the best fit for the rs13405699 polymorphism. Conclusion: This study represents the first confirmation of the association between the rs13405699 SNP at 2q31.1 and MPB within the Han Chinese population, thereby enhancing our understanding of the genetic underpinnings of MPB.

Sirtuin 1/sirtuin 3 are robust lysine delactylases and sirtuin 1-mediated delactylation regulates glycolysis.

Lysine lactylation (Kla), an epigenetic mark triggered by lactate during glycolysis, including the Warburg effect, bridges metabolism and gene regulation. Enzymes such as p300 and HDAC1/3 have been pivotal in deciphering the regulatory dynamics of Kla, though questions about additional regulatory enzymes, their specific Kla substrates, and the underlying functional mechanisms persist. Here, we identify SIRT1 and SIRT3 as key "erasers" of Kla, shedding light on their selective regulation of both histone and non-histone proteins. Proteomic analysis in SIRT1/SIRT3 knockout HepG2 cells reveals distinct substrate specificities toward Kla, highlighting their unique roles in cellular signaling. Notably, we highlight the role of specific Kla modifications, such as those on the M2 splice isoform of pyruvate kinase (PKM2), in modulating metabolic pathways and cell proliferation, thereby expanding Kla's recognized functions beyond epigenetics. Therefore, this study deepens our understanding of Kla's functional mechanisms and broadens its biological significance.

Single-cell transcriptome analysis of the mouse lungs during the injury and recovery periods after lipopolysaccharide administration.

OBJECTIVE: This study sought to investigate the cellular and molecular alterations during the injury and recovery periods of ALI and develop effective treatments for ALI. METHODS: Pulmonary histology at 1, 3, 6, and 9 days after lipopolysaccharide administration mice were assessed. An unbiased single-cell RNA sequencing was performed in alveoli tissues from injury (day 3) and recovery (day 6) mice after lipopolysaccharide administration. The roles of Fpr2 and Dpp4 in ALI were assessed. RESULTS: The most severe lung injury occurred on day 3, followed by recovery entirely on day 9 after lipopolysaccharide administration. The numbers of Il1a+ neutrophils, monocytes/macrophages, and Cd4+ and Cd8+ T cells significantly increased at day 3 after LPS administration; subsequently, the number of Il1a+ neutrophils greatly decreased, the numbers of monocytes/macrophages and Cd4+ and Cd8+ T cells continuously increased, and the number of resident alveolar macrophages significantly increased at day 6. The interactions between monocytes/macrophages and pneumocytes during the injury period were enhanced by the Cxcl10/Dpp4 pair, and inhibiting Dpp4 improved ALI significantly, while inhibiting Fpr2 did not. CONCLUSIONS: Our results offer valuable insights into the cellular and molecular mechanisms underlying its progression and identify Dpp4 as an effective therapeutic target for ALI.

MEK inhibition prevents CAR-T cell exhaustion and differentiation via downregulation of c-Fos and JunB.

Clinical evidence supports the notion that T cell exhaustion and terminal differentiation pose challenges to the persistence and effectiveness of chimeric antigen receptor-T (CAR-T) cells. MEK1/2 inhibitors (MEKIs), widely used in cancer treatment due to their ability to inhibit aberrant MAPK signaling, have shown potential synergistic effects when combined with immunotherapy. However, the impact and mechanisms of MEKIs on CAR-T cells remain uncertain and controversial. To address this, we conducted a comprehensive investigation to determine whether MEKIs enhance or impair the efficacy of CAR-T cells. Our findings revealed that MEKIs attenuated CAR-T cell exhaustion and terminal differentiation induced by tonic signaling and antigen stimulation, thereby improving CAR-T cell efficacy against hematological and solid tumors. Remarkably, these effects were independent of the specific scFvs and costimulatory domains utilized in CARs. Mechanistically, analysis of bulk and single-cell transcriptional profiles demonstrates that the effect of MEK inhibition was related to diminish anabolic metabolism and downregulation of c-Fos and JunB. Additionally, the overexpression of c-Fos or JunB in CAR-T cells counteracted the effects of MEK inhibition. Furthermore, our Cut-and-Tag assay revealed that MEK inhibition downregulated the JunB-driven gene profiles associated with exhaustion, differentiation, anergy, glycolysis, and apoptosis. In summary, our research unveil the critical role of the MAPK-c-Fos-JunB axis in driving CAR-T cell exhaustion and terminal differentiation. These mechanistic insights significantly broaden the potential application of MEKIs to enhance the effectiveness of CAR-T therapy.

Unfractionated Heparin Enhances Sepsis Prognosis Through Inhibiting Drp1-Mediated Mitochondrial Quality Imbalance.

Unfractionated heparin (UFH) is commonly used as an anticoagulant in sepsis treatment and has recently been found to have non-anticoagulant effects, but underlying mechanisms remain unclear. This retrospective clinical data showed that UFH has significant protective effects in sepsis compared to low-molecular-weight heparin and enoxaparin, indicating potential benefits of its non-anticoagulant properties. Recombinant protein chip screening, surface plasmon resonance, and molecular docking data demonstrated that UFH specifically bound to the cytoplasmic Drp1 protein through its zone 2 non-anticoagulant segment. In-vitro experiments verified that UFH's specific binding to Drp1 suppressed Drp1 translocation to mitochondria following "sepsis" challenge, thereby improving mitochondrial morphology, function and metabolism in vascular endothelial cells. Consequently, UHF comprehensively protected mitochondrial quality, thus reducing vascular leakage and improving prognosis in a sepsis rat model. These findings highlight the potential of UFH as a sepsis treatment strategy targeting non-anticoagulation mechanism.

Human factors considerations of Interaction between wearers and intelligent lower-limb prostheses: a prospective discussion.

Compared to traditional lower-limb prostheses (LLPs), intelligent LLPs are more versatile devices with emerging technologies, such as microcontrollers and user-controlled interfaces (UCIs). As emerging technologies allow a higher level of automation and more involvement from wearers in the LLP setting adjustments, the previous framework established to study human factors elements that affect wearer-LLP interaction may not be sufficient to understand the new elements (e.g., transparency) and dynamics in this interaction. In addition, the increased complexity of interaction amplifies the limitations of the traditional evaluation approaches of wearer-LLP interaction. Therefore, to ensure wearer acceptance and adoption, from a human factors perspective, we propose a new framework to introduce elements and usability requirements for the wearer-LLP interaction. This paper organizes human factors elements that appear with the development of intelligent LLP technologies into three aspects: wearer, device, and task by using a classic model of the human-machine systems. By adopting Nielsen's five usability requirements, we introduce learnability, efficiency, memorability, use error, and satisfaction into the evaluation of wearer-LLP interaction. We identify two types of wearer-LLP interaction. The first type, direct interaction, occurs when the wearer continuously interacts with the intelligent LLP (primarily when the LLP is in action); the second type, indirect interaction, occurs when the wearer initiates communication with the LLP usually through a UCI to address the current or foreseeable challenges. For each type of interaction, we highlight new elements, such as device transparency and prior knowledge of the wearer with the UCI. In addition, we redefine the usability goals of two types of wearer-LLP interaction with Nelson's five usability requirements and review methods to evaluate the interaction. Researchers and designers for intelligent LLPs should consider the new device elements that may additionally influence wearers' acceptance and the need to interpret findings within the constraints of the specific wearer and task characteristics. The proposed framework can also be used to organize literature and identify gaps for future directions. By adopting the holistic usability requirements, findings across empirical studies can be more comparable. At the end of this paper, we discuss research trends and future directions in the human factors design of intelligent LLPs.

Electrophotocatalysis for Organic Synthesis.

Electrocatalysis and photocatalysis have been the focus of extensive research efforts in organic synthesis in recent decades, and these powerful strategies have provided a wealth of new methods to construct complex molecules. Despite these intense efforts, only recently has there been a significant focus on the combined use of these two modalities. Nevertheless, the past five years have witnessed rapidly growing interest in the area of electrophotocatalysis. This hybrid strategy capitalizes on the enormous benefits of using photons as reagents while also employing an electric potential as a convenient and tunable source or sink of electrons. Research on this topic has led to a number of methods for C-H functionalization, reductive cross-coupling, and olefin addition among others. This field has also seen the use of a broad range of catalyst types, including both metal and organocatalysts. Of particular note has been work with open-shell photocatalysts, which tend to have comparatively large redox potentials. Electrochemistry provides a convenient means to generate such species, making electrophotocatalysis particularly amenable to this intriguing class of redox catalyst. This review surveys methods in the area of electrophotocatalysis as applied to organic synthesis, organized broadly into oxidative, reductive, and redox neutral transformations.

Acetylcholine receptor-ß inhibition by interleukin-6 in skeletal muscles contributes to modulating neuromuscular junction during aging.

BACKGROUND: Aging-related strength decline contributes to physiological deterioration and is a good predictor of poor prognosis. However, the mechanisms underlying neuromuscular junction disorders affecting contraction in aging are not well described. We hypothesized that the autocrine effect of interleukin (IL)-6 secreted by skeletal muscle inhibits acetylcholine receptor (AChR) expression, potentially causing aging-related strength decline. Therefore, we investigated IL-6 and AChR ß-subunit (AChR-ß) expression in the muscles and sera of aging C57BL/6J mice and verified the effect of IL-6 on AChR-ß expression. METHODS: Animal experiments, in vitro studies, bioinformatics, gene manipulation, dual luciferase reporter gene assays, and chromatin immunoprecipitation experiments were used to explore the role of the transcription cofactor peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α) and its interacting transcription factors in the IL-6-mediated regulation of AChR-ß expression. RESULTS: IL-6 expression gradually increased during aging, inhibiting AChR-ß expression, which was reversed by tocilizumab. Both tocilizumab and the PGC1α agonist reversed the inhibiting effect of IL-6 expression on AChR-ß. Compared to inhibition of signal transducer and activator of transcription 3, extracellular signal-regulated kinases 1/2 (ERK1/2) inhibition suppressed the effects of IL-6 on AChR-ß and PGC1α. In aging mouse muscles and myotubes, myocyte enhancer factor 2 C (MEF2C) was recruited by PGC1α, which directly binds to the AChR-ß promoter to regulate its expression. CONCLUSIONS: This study verifies AChR-ß regulation by the IL-6/IL-6R-ERK1/2-PGC1α/MEF2C pathway. Hence, evaluating muscle secretion, myokines, and AChRs at an earlier stage to determine pathological progression is important. Moreover, developing intervention strategies for monitoring, maintaining, and improving muscle structure and function is necessary.

Integrating UPLC-Q-Exactive Orbitrap/MS, Network pharmacology and experimental validation to reveal the potential mechanism of Kadsuracoccinea roots in Colon Cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Kadsura coccinea roots are a traditional folk medicine used to treat gastrointestinal diseases. In recent years, research on K. coccinea has predominantly focused on the analysis of chemical composition and screening for activity, but there is a scarcity of studies that employ mass spectrometry to analyze Kadsura coccinea roots. AIM OF THE STUDY: This study aimed to characterize the chemical composition of K. coccinea roots and explore the pharmacological mechanisms with network pharmacology. Cell assay and Western blot analysis were used to verify the pharmacological mechanism of the main compounds in K. coccinea roots. MATERIALS AND METHODS: UPLC-Q-Exactive Orbitrap/MS was used for chemical analysis of K. coccinea roots, and the compounds were identified by employing diagnostic product ions, fragmentation patterns, ChemSpider, and in-house databases. Network pharmacology was employed to estimate the pathways related to pharmacological mechanisms. In addition, MTT assay was conducted to determine the inhibitory activity of colon cancer cell lines, and their apoptotic abilities were evaluated by flow cytometry and Western blot. RESULTS: The UPLC-Q-Exactive Orbitrap/MS identified a total of 54 compounds in K. coccinea roots. The 54 compounds were subjected to network pharmacology analysis, exploring the pharmacological action of the main components of K. coccinea roots. The common targets between the compounds and colon cancer comprised 2009 GO biological process items and 186 KEGG signal pathways. Flow cytometry indicated that treatments with 20 µM of the above-named compounds resulted in an apoptosis rate of 16.6%, 79.7%, and 22.2% in HCT-116 cells, respectively. Meanwhile, Western blot analysis confirmed that the compounds promoted the expression of Bax and Caspase-3 level expression. CONCLUSION: The findings demonstrated that K. coccinea roots can treat colon cancer through multiple components, targets, and pathways. This study revealed the effective components and molecular mechanisms of K. coccinea, which were preliminarily verified using in vitro experiments.

Combination of different local anesthetic adjunct for supraclavicular brachial plexus block after arthroscopic shoulder surgery: a prospective randomized controlled trial.

BACKGROUND: Acute pain is a major concern after arthroscopic shoulder surgery, supraclavicular brachial plexus blockade has shown favorable postoperative analgesic effects. However, its duration of analgesia does not meet clinical needs. We aimed to explore whether the combination of different local anesthetic adjunct can prolong the analgesic duration of supraclavicular brachial plexus block for arthroscopic shoulder surgery. METHODS: In this prospective randomized controlled trial, we allocated 80 patients into four groups: Group DMD (dexamethasone 10 mg + ropivacaine 100 mg + dexmedetomidine 50 µg + magnesium sulfate 250 mg), Group DM (ropivacaine 100 mg + dexmedetomidine 50 µg + magnesium sulfate 250 mg), Group M (ropivacaine 100 mg + magnesium sulfate 250 mg) and Group D (ropivacaine 100 mg + dexmedetomidine 50 µg). The primary outcome was the time to first request for analgesia. Secondary outcome measures included cumulative opioid consumption at 6, 12, 18, 24, and 48 h postoperatively, VAS scores at 6, 12, 18, 24, and 48 h postoperatively and so on. RESULTS: The time to first request for analgesia in Group DMD was significantly longer than Group DM (P = 0.011) and Group M (P = 0.003). The cumulative opioid consumption at 18 h postoperatively in Group DMD was significantly lower than in Group DM (P = 0.002) and Group M (P = 0.007). The cumulative opioid consumption at 24 h postoperatively in Group DMD was significantly lower than in Group DM (P = 0.016). The VAS score at 6 h postoperatively in Group DMD was significantly lower than in Group DM and Group M. The VAS score at 12 h postoperatively in Group DMD was significantly lower than in Group M. For American Shoulder and Elbow Surgeons Score, Group DMD had a better score than Group DM and Group D. CONCLUSIONS: The analgesic efficacy of supraclavicular brachial plexus blockade combined with dexamethasone, magnesium sulfate, and dexmedetomidine is significantly superior to the combination of magnesium sulfate and dexmedetomidine, and significantly superior to the use of magnesium sulfate alone. TRIAL REGISTRATION: This trial was registered in Chinese Clinical Trial Registry. (ChiCTR2200061181, Date of registration: June 15, 2022, http://www.chictr.org.cn ).

Administration of Lactobacillus plantarum GUANKE alleviates SARS-CoV-2-induced pneumonia in mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets epithelial cells in the respiratory tract, triggering an acute proinflammatory response and chronic lung inflammation. Probiotic supplementation has shown promise in reducing the nasopharyngeal SARS-CoV-2 viral load, diminishing symptom frequency and duration, and mitigating inflammation; thus, it is a potential strategy for treating coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2 infection. In this study, we evaluated the effects of the oral administration of the Lactobacillus plantarum GUANKE strain, a gram-positive bacterium originally isolated from a healthy individual, on SARS-CoV-2 infection in a human ACE2 transgenic mouse model. We found that GUANKE significantly reduced inflammatory cell infiltration and pulmonary interstitial exudation in mice. The transcription of CCL2, TNFA, IL1B, IL6, and IL17C in the lungs was reduced. The protein levels of TNF-α, IL-1ß, IL-6, and IL-17 in the lungs were significantly lower in GUANKE-treated mice than in control mice. The viral load in GUANKE-treated mice was lower than that in saline-treated mice, although this difference did not reach statistical significance. L. plantarum GUANKE can decrease SARS-CoV-2-induced lung inflammation in mice, suggesting its potential for use as an agent for treating SARS-CoV-2 infection. IMPORTANCE: Most otherwise healthy individuals develop only mild or moderate symptoms of coronavirus disease 2019 (COVID-19) caused by current strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and virus replication is mainly confined to the upper respiratory tract; however, the virus can infect the lower respiratory tract and promote inflammation. Probiotic supplementation has been shown to reduce nasopharyngeal SARS-CoV-2 viral load, reduce the overall number and duration of symptoms, and attenuate inflammation in clinical trials. We showed that a novel L. plantarum GUANKE strain alleviated SARS-CoV-2-induced pneumonia in mice. The transcription and production of inflammatory cytokines were suppressed, and GUANKE moderately reduced the viral load. L. plantarum GUANKE has the potential to become a candidate drug for the treatment of COVID-19 or other viral respiratory infections.

Methane Production Is More Sensitive to Temperature Increase than Aerobic and Anaerobic Methane Oxidation in Chinese Paddy Soils.

Methane emissions from paddy fields can increase under future warming scenarios. Nevertheless, a comprehensive comparison of the temperature sensitivity of methane-related microbial processes remains elusive. Here, we revealed that the temperature sensitivity of methane production (activation energy (Ea) = 0.94 eV; 95% confidence interval (CI), 0.78-1.10 eV) and aerobic (Ea = 0.49 eV; 95% CI, 0.34-0.65 eV) and anaerobic (Ea = 0.46 eV; 95% CI, 0.30-0.62 eV) methane oxidation exhibited notable spatial heterogeneity across 12 Chinese paddy fields spanning 35° longitude and 18° latitude. In addition, the Ea values of aerobic and anaerobic methane oxidation were significantly positively and negatively correlated to the latitude, respectively, while there was no significant correlation between the Ea of methane production and the latitude. Overall, there were no soil factors that had a significant effect on the Ea of methane production. The Ea of aerobic methane oxidation was primarily influenced by the contents of ammonium and clay, whereas the Ea of anaerobic methane oxidation was mainly influenced by the conductivity. Despite the variation, the overall temperature sensitivity of methane production was significantly higher than that of oxidation at a continental scale; therefore, an increase in the emission of methane from paddy fields will be predicted under future warming. Taken together, our study revealed the characteristics of temperature sensitivity of methane production and aerobic and anaerobic methane oxidation simultaneously in Chinese paddy fields, highlighting the potential roles of soil factors in influencing temperature sensitivity.