Extracellular BSA-degrading SAPs in the rare pathogen Meyerozyma guilliermondii strain SO as potential virulence factors in candidiasis.

Meyerozyma guilliermondii (Candida guilliermondii) is one of the Candida species associated with invasive candidiasis. With the potential for expressing industrially important enzymes, M. guilliermondii strain SO possessed 99 % proteome similarity with the clinical ATCC 6260 isolate and showed pathogenicity towards zebrafish embryos. Recently, three secreted aspartyl proteinases (SAPs) were computationally identified as potential virulence factors in this strain without in vitro verification of SAP activity. The quantification of Candida SAPs activity in liquid broth were also scarcely reported. Thus, this study aimed to characterize M. guilliermondii strain SO's ability to produce SAPs (MgSAPs) in different conditions (morphology and medium) besides analyzing its growth profile. MgSAPs' capability to cleave bovine serum albumin (BSA) was also determined to propose that MgSAPs as the potential virulence factors compared to the avirulent Saccharomyces cerevisiae. M. guilliermondii strain SO produced more SAPs (higher activity) in yeast nitrogen base-BSA-dextrose broth compared to yeast extract-BSA-dextrose broth despite insignificantly different SAP activity in both planktonic and biofilm cells. FeCl3 supplementation significantly increased the specific protein activity (∼40 %). The BSA cleavage by MgSAPs at an acidic pH was proven through semi-quantitative SDS-PAGE, sharing similar profile with HIV-1 retropepsin. The presented work highlighted the MgSAPs on fungal cell wall and extracellular milieu during host infection could be corroborated to the quantitative production in different growth modes presented herein besides shedding lights on the potential usage of retropepsin's inhibitors in treating candidiasis. Molecular and expression analyses of MgSAPs and their deletion should be further explored to attribute their respective virulence effects.

Remote ischemic conditioning prevents ischemic cerebrovascular events in children with moyamoya disease: a randomized controlled trial.

BACKGROUND: Moyamoya disease (MMD) is a significant cause of childhood stroke and transient ischemic attacks (TIAs). This study aimed to assess the safety and efficacy of remote ischemic conditioning (RIC) in children with MMD. METHODS: In a single-center pilot study, 46 MMD patients aged 4 to 14 years, with no history of reconstructive surgery, were randomly assigned to receive either RIC or sham RIC treatment twice daily for a year. The primary outcome measured was the cumulative incidence of major adverse cerebrovascular events (MACEs). Secondary outcomes included ischemic stroke, recurrent TIA, hemorrhagic stroke, revascularization rates, and clinical improvement assessed using the patient global impression of change (PGIC) scale during follow-up. RIC-related adverse events were also recorded, and cerebral hemodynamics were evaluated using transcranial Doppler. RESULTS: All 46 patients completed the final follow-up (23 each in the RIC and sham RIC groups). No severe adverse events associated with RIC were observed. Kaplan-Meier analysis indicated a significant reduction in MACEs frequency after RIC treatment [log-rank test (Mantel-Cox), P = 0.021]. At 3-year follow-up, two (4.35%) patients had an ischemic stroke, four (8.70%) experienced TIAs, and two (4.35%) underwent revascularization as the qualifying MACEs. The clinical improvement rate in the RIC group was higher than the sham RIC group on the PGIC scale (65.2% vs. 26.1%, P < 0.01). No statistical difference in cerebral hemodynamics post-treatment was observed. CONCLUSIONS: RIC is a safe and effective adjunct therapy for asymptomatic children with MMD. This was largely due to the reduced incidence of ischemic cerebrovascular events.

Personalized, parcel-guided non-invasive transcranial magnetic stimulation for the treatment of post-concussive syndrome: safety and proof of concept.

OBJECTIVE: To determine the safety and proof of concept of a parcel-guided, repetitive Transcranial Magnetic Stimulation (rTMS) in patients who develop a heterogeneous array of symptoms, known collectively as post-concussive syndrome (PCS), following traumatic brain injury (TBI). METHODS: We performed a retrospective review of off-label, individualized, parcel-guided rTMS in 19 patients from December 2020 to May 2023. Patients had at least one instance of mild, moderate, or severe TBI and developed symptoms not present prior to injury. rTMS targets were identified based on machine learning connectomic software using functional connectivity anomaly matrices compared to healthy controls. EuroQol (EQ-5D), as a measurement of quality of life, and additional questionnaires dependent on individual's symptoms were submitted prior to, after, and during follow-up from rTMS. RESULTS: Nineteen patients showed improvement in EQ-5D and Rivermead Post Concussion Symptoms Questionnaires - 3 after treatment and follow-up. For nine patients who developed depression, five (55%) attained response and remission based on the Beck Depression Inventory after treatment. Eight of ten patients with anxiety had a clinically significant reduction in Generalized Anxiety Disorder-7 scores during follow-up. CONCLUSION: Parcel-guided rTMS is safe and may be effective in reducing PCS symptoms following TBI and should incite further controlled studies.

The influence of sleep disorders on perioperative neurocognitive disorders among the elderly: A narrative review.

This review comprehensively assesses the epidemiology, interaction, and impact on patient outcomes of perioperative sleep disorders (SD) and perioperative neurocognitive disorders (PND) in the elderly. The incidence of SD and PND during the perioperative period in older adults is alarmingly high, with SD significantly contributing to the occurrence of postoperative delirium. However, the clinical evidence linking SD to PND remains insufficient, despite substantial preclinical data. Therefore, this study focuses on the underlying mechanisms between SD and PND, underscoring that potential mechanisms driving SD-induced PND include uncontrolled central nervous inflammation, blood-brain barrier disruption, circadian rhythm disturbances, glial cell dysfunction, neuronal and synaptic abnormalities, impaired central metabolic waste clearance, gut microbiome dysbiosis, hippocampal oxidative stress, and altered brain network connectivity. Additionally, the review also evaluates the effectiveness of various sleep interventions, both pharmacological and nonpharmacological, in mitigating PND. Strategies such as earplugs, eye masks, restoring circadian rhythms, physical exercise, noninvasive brain stimulation, dexmedetomidine, and melatonin receptor agonists have shown efficacy in reducing PND incidence. The impact of other sleep-improvement drugs (e.g., orexin receptor antagonists) and methods (e.g., cognitive-behavioral therapy for insomnia) on PND is still unclear. However, certain drugs used for treating SD (e.g., antidepressants and first-generation antihistamines) may potentially aggravate PND. By providing valuable insights and references, this review aimed to enhance the understanding and management of PND in older adults based on SD.

Effectiveness of electroacupuncture on postoperative ileus prevention after abdominal surgery: A systematic review and trial sequential analysis of randomized controlled trials.

BACKGROUND: We aimed to verify the effectiveness of electroacupuncture on postoperative ileus prevention after abdominal surgery by meta-analysis and trial sequential analysis (TSA). METHODS: From inception to May 14, 2024, PubMed, the Cochrane Library, Web of Science, and Embase databases were searched. TSA was used to determine an optimal sample size and control false-positive findings. The primary outcome was the time to first defecation (hours). RESULTS: Fourteen studies were included, with 1105 participants. Meta-analysis and TSA revealed firm evidence for benefits that electroacupuncture shorted the time to first defecation (mean difference [MD] -12.73 h, I2 = 22%, P < 0.01), the time to first flatus (MD -7.03 h, I2 = 25%, P < 0.01), the time to start of sips of water (MD -12.02 h, I2 = 0%, P < 0.01), and the time to start of liquid diet (MD -12.97 h, I2 = 0%, P < 0.01) compared with usual care. While compared with sham electroacupuncture, meta-analysis and TSA also confirmed that electroacupuncture shortened the time to first defecation (MD -10.81 h, I2 = 31%, P = 0.02) and the time to first flatus (MD -10.81 h, I2 = 0%, P < 0.01). However, TSA revealed that firm evidence for benefit or futility was not reached for the length of hospital stay and the rates of postoperative prolonged ileus. CONCLUSIONS: Electroacupuncture shortened the duration of postoperative ileus in patients undergoing abdominal surgery, and the adverse events related to electroacupuncture were minor. Further investigation of the effect of electroacupuncture on the risk of prolonged postoperative ileus is warranted in the future.

Discernible interindividual patterns of global efficiency decline during theoretical brain surgery.

The concept of functional localization within the brain and the associated risk of resecting these areas during removal of infiltrating tumors, such as diffuse gliomas, are well established in neurosurgery. Global efficiency (GE) is a graph theory concept that can be used to simulate connectome disruption following tumor resection. Structural connectivity graphs were created from diffusion tractography obtained from the brains of 80 healthy adults. These graphs were then used to simulate parcellation resection in every gross anatomical region of the cerebrum by identifying every possible combination of adjacent nodes in a graph and then measuring the drop in GE following nodal deletion. Progressive removal of brain parcellations led to patterns of GE decline that were reasonably predictable but had inter-subject differences. Additionally, as expected, there were deletion of some nodes that were worse than others. However, in each lobe examined in every subject, some deletion combinations were worse for GE than removing a greater number of nodes in a different region of the brain. Among certain patients, patterns of common nodes which exhibited worst GE upon removal were identified as "connectotypes". Given some evidence in the literature linking GE to certain aspects of neuro-cognitive abilities, investigating these connectotypes could potentially mitigate the impact of brain surgery on cognition.

Post-traumatic hyperoxia after pediatric TBI.

OBJECTIVE: Hyperoxia has been suggested as a mechanism for secondary injury following adult traumatic brain injury (TBI), but its effects have not been well described in pediatric patients. METHODS: Pediatric (≤18yo) TBI patients were identified in a prospective institutional registry from October 2008 to April 2022. The first, highest, and the Area Under the Curve (AUC) PaO2 in the first 24 hours were collected and calculated for each patient from arterial blood gas reports after admission to the ICU. Neurological outcome after 6 months was measured using dichotomized modified Rankin Scale (mRS) and Glasgow Outcome Scale - Extended (GOS-E). Multivariable logistic regression models were used to determine if the three measurements for hyperoxia predicted an unfavorable outcome after controlling for well-established clinical and imaging predictors of outcome. RESULTS: We identified 98 pediatric patients with severe accidental TBI during the study period. Hyperoxia (PaO2 > 300 mmHg) occurred in 33% of the patients. The presence of elevated PaO2 values, determined by all three evaluations of hyperoxia, was not associated with unfavorable outcome after 6 months. CONCLUSION: Utilizing multiple methods to assess exposure, hyperoxia was present in a substantial number of patients with severe TBI but was not associated with an unfavorable outcome.

METTL14 downregulation drives S100A4+ monocyte-derived macrophages via MyD88/NF-κB pathway to promote MAFLD progression.

Without intervention, a considerable proportion of patients with metabolism-associated fatty liver disease (MAFLD) will progress from simple steatosis to metabolism-associated steatohepatitis (MASH), liver fibrosis, and even hepatocellular carcinoma. However, the molecular mechanisms that control progressive MAFLD have yet to be fully determined. Here, we unraveled that the expression of the N6-methyladenosine (m6A) methyltransferase METTL14 is remarkably downregulated in the livers of both patients and several murine models of MAFLD, whereas hepatocyte-specific depletion of this methyltransferase aggravated lipid accumulation, liver injury, and fibrosis. Conversely, hepatic Mettl14 overexpression alleviated the above pathophysiological changes in mice fed on a high-fat diet (HFD). Notably, in vivo and in vitro mechanistic studies indicated that METTL14 downregulation decreased the level of GLS2 by affecting the translation efficiency mediated by YTHDF1 in an m6A-depedent manner, which might help to form an oxidative stress microenvironment and accordingly recruit Cx3cr1+Ccr2+ monocyte-derived macrophages (Mo-macs). In detail, Cx3cr1+Ccr2+ Mo-macs can be categorized into M1-like macrophages and S100A4-positive macrophages and then further activate hepatic stellate cells (HSCs) to promote liver fibrosis. Further experiments revealed that CX3CR1 can activate the transcription of S100A4 via CX3CR1/MyD88/NF-κB signaling pathway in Cx3cr1+Ccr2+ Mo-macs. Restoration of METTL14 or GLS2, or interfering with this signal transduction pathway such as inhibiting MyD88 could ameliorate liver injuries and fibrosis. Taken together, these findings indicate potential therapies for the treatment of MAFLD progression.

A Serum Pharmacochemistry and Network Pharmacology-based Approach to Study the Anti-depressant Effect of Chaihu-Shugan San.

AIMS: The aim of this study is to explore the anti-depressant mechanism of Chaihu- Shugan San based on serum medicinal chemistry and network pharmacology methods. BACKGROUND: Depression lacks effective treatments, with current anti-depressants ineffective in 40% of patients. Chaihu-Shugan San (CHSGS) is a well-known traditional Chinese medicine compound to treat depression. However, the chemical components and the underlying mechanisms targeting the liver and brain in the anti-depressant effects of CHSGS need to be elucidated. METHODS: The chemical components of CHSGS in most current network pharmacology studies are screened from TCMSP and TCMID databases. In this study, we investigated the mechanism and material basis of soothing the liver and relieving depression in the treatment of depression by CHSGS based on serum pharmacochemistry. The anti-depressant mechanism of CHSGS was further verified by proteomics and high-throughput data. RESULTS: Through serum medicinal chemistry, we obtained 9 bioactive substances of CHSGS. These ingredients have good human oral bioavailability and are non-toxic. Based on liver ChIPseq data, CHSGS acts on 8 targets specifically localized in the liver, such as FGA, FGB, and FGG. The main contributors to CHSGS soothing the liver qi targets are hesperetin, nobiletin, ferulic acid, naringin and albiflorin. In addition, network pharmacology analysis identified 9 blood components of CHSGS that corresponded to 63 anti-depressant targets in the brain. Among them, nobiletin has the largest number of anti-depressant targets, followed by glycyrrhizic acid, ferulic acid, albiflorin and hesperetin. We also validated the anti-depressant mechanism of CHSGS based on hippocampal proteomics. CHSGS exerts anti-depressant effects on synaptic structure and neuronal function by targeting multiple synapse related proteins. CONCLUSION: This study not only provides a theoretical basis for further expanding the clinical application of CHSGS, but also provides a series of potential lead compounds for the development of depression drugs.

Simultaneous SERS Sensing of Cysteine and Homocysteine in Blood Based on the CBT-Cys Click Reaction: Toward Precisive Diagnosis of Schizophrenia.

At present, there is a lack of sufficiently specific laboratory diagnostic indicators for schizophrenia. Serum homocysteine (Hcy) levels have been found to be related to schizophrenia. Cysteine (Cys) is a demethylation product in the metabolism of Hcy, and they always coexist with highly similar structures in vivo. There are few reports on the use of Cys as a diagnostic biomarker for schizophrenia in collaboration with Hcy, mainly because the rapid, economical, accurate, and high-throughput simultaneous detection of Cys and Hcy in serum is highly challenging. Herein, a click reaction-based surface-enhanced Raman spectroscopy (SERS) sensor was developed for simultaneous and selective detection of Cys and Hcy. Through the efficient and specific CBT-Cys click reaction between the probe containing cyan benzothiazole and Cys/Hcy, the tiny methylene difference between the molecular structures of Cys and Hcy was converted into the difference between the ring skeletons of the corresponding products that could be identified by plasmonic silver nanoparticle enhanced molecular fingerprint spectroscopy to realize discriminative detection. Furthermore, the SERS sensor was successfully applied to the detection in related patient serum samples, and it was found that the combined analysis of Cys and Hcy can improve the diagnostic accuracy of schizophrenia compared to a single indicator.

Erythropoietin-derived peptide ARA290 mediates brain tissue protection through the ß-common receptor in mice with cerebral ischemic stroke.

AIM: To explore the neuroprotective effects of ARA290 and the role of ß-common receptor (ßCR) in a mouse model of middle cerebral artery occlusion (MCAO). METHODS: This study included male C57BL/6J mice that underwent MCAO and reperfusion. The neuroprotective effect of ARA290 on MCAO-induced brain injury was investigated using neurological function tests (Longa and modified neurological severity score). Cerebral infarction was examined by 2, 3, 5-triphenyl tetrazolium chloride staining, neuronal apoptosis was assessed by immunofluorescence staining, blood parameters were measured using a flow cytometry-based automated hematology analyzer, liquid chromatography with tandem mass spectrometry was used to identify the serum metabolomics signature, inflammatory cytokines and liver index were detected by commercially available kits, and the protein levels of the erythropoietin (EPO) receptor and ßCR were measured by western blot. RESULTS: ARA290 exerted a qualitatively similar neuroprotective effect after MCAO as EPO. ARA290 significantly reduced neuronal apoptosis and the level of inflammatory cytokines in the brain tissue. However, ARA290's neuroprotective effect was significantly suppressed following the injection of siRNA against ßCR. CONCLUSION: ARA290 provided a neuroprotective effect via ßCR in cerebral ischemic mice without causing erythropoiesis. This study provides novel insights into the role of ARA290 in ischemic stroke intervention.

Fractionated lignin as a green compatibilizer to improve the compatibility of poly (butylene adipate-co-terephthalate) /polylactic acid composites.

Blending poly (butylene adipate-co-terephthalate) (PBAT) and polylactic acid (PLA) is a cost-effective strategy to obtain biodegradable plastic with complementary properties. However, the incompatibility between PBAT and PLA is a great challenge for fabricating high-performance composite films. Herein, the ethyl acetate fractionated lignin with the small glass transition temperature and low molecular weight was achieved and incorporated into the PBAT/PLA composite as a compatibilizer. The fractionated lignin can be uniformly dispersed within the PBAT/PLA matrix through a melt blending process and interact with the molecular chain of PBAT and PLA as a bonding bridge, which enhances the intermolecular interactions and reduces the interfacial tension of PBAT/PLA. By adding fractionated lignin, the tensile strength of the PBAT/PLA composite increased by 35.4 % and the yield strength increased by 37.7 %. Owing to lignin, the composite films possessed the ultraviolet shielding function and exhibited better water vapor barrier properties (1.73 ± 0.08 × 10-13 g·cm/cm2·s·Pa). This work conclusively demonstrated that fractionated lignin can be used as a green compatibilizer and a low-cost functional filler for PBAT/PLA materials, and provides guidance for the application of lignin in biodegradable plastics.

Rapid and sensitive detection of Salmonella in agro-Food and environmental samples: A review of advances in rapid tests and biosensors.

Salmonella is as an intracellular bacterium, causing many human fatalities when the host-specific serotypes reach the host gastrointestinal tract. Nontyphoidal Salmonella are responsible for numerous foodborne outbreaks and product recalls worldwide whereas typhoidal Salmonella are responsible for Typhoid fever cases in developing countries. Yet, Salmonella-related foodborne disease outbreaks through its food and water contaminations have urged the advancement of rapid and sensitive Salmonella-detecting methods for public health protection. While conventional detection methods are time-consuming and ineffective for monitoring foodstuffs with short shelf lives, advances in microbiology, molecular biology and biosensor methods have hastened the detection. Here, the review discusses Salmonella pathogenic mechanisms and its detection technology advancements (fundamental concepts, features, implementations, efficiency, benefits, limitations and prospects). The time-efficiency of each rapid test method is discussed in relation to their limit of detections (LODs) and time required from sample enrichment to final data analysis. Importantly, the matrix effects (LODs and sample enrichments) were compared within the methods to potentially speculate Salmonella detection from environmental, clinical or food matrices using certain techniques. Although biotechnological advancements have led to various time-efficient Salmonella-detecting techniques, one should consider the usage of sophisticated equipment to run the analysis by moderately to highly trained personnel. Ultimately, a fast, accurate Salmonella screening that is readily executed by untrained personnels from various matrices, is desired for public health procurement.

Surface Lattice Modulation Enables Stable Cycling of High-Loading All-solid-state Batteries at High Voltages.

Halide solid electrolytes, known for their high ionic conductivity at room temperature and good oxidative stability, face notable challenges in all-solid-state Li-ion batteries (ASSBs), especially with unstable cathode/solid electrolyte (SE) interface and increasing interfacial resistance during cycling. In this work, we have developed an Al3+-doped, cation-disordered epitaxial nanolayer on the LiCoO2 surface by reacting it with an artificially constructed AlPO4 nanoshell; this lithium-deficient layer featuring a rock-salt-like phase effectively suppresses oxidative decomposition of Li3InCl6 electrolyte and stabilizes the cathode/SE interface at 4.5 V. The ASSBs with the halide electrolyte Li3InCl6 and a high-loading LiCoO2 cathode demonstrated high discharge capacity and long cycling life from 3 to 4.5 V. Our findings emphasize the importance of specialized cathode surface modification in preventing SE degradation and achieving stable cycling of halide-based ASSBs at high voltages.

Ultrasound blood flow characteristics changes in fetal umbilical artery thrombosis: A retrospective analysis.

BACKGROUND: Umbilical artery thrombosis (UAT) is extremely uncommon and leads to adverse perinatal outcomes. Hypercoagulation of blood in pregnant women is suspected to be an important risk for UAT. Ultrasound is an effective way to detect thrombosis. The mother can monitor her own fetal health using ultrasound, which enables her to take preventative action in case of emergency. AIM: To investigate ultrasonic blood signal after UAT in the umbilical artery, and evaluate the relationship between hypercoagulability and UAT. METHODS: We described a case of a newly formed UAT with markedly altered ultrasonic indices of umbilical artery blood flow, and retrospectively studied it with 18 UAT patients confirmed by histopathology from October 2019 and March 2023 in Xiamen Women and Children's Hospital. Patients' information was collected from medical archives, including maternal clinical data, neonatal outcomes, pathological findings and ultrasonic indices of umbilical artery blood flow, such as systolic-diastolic duration ratio (S/D), resistance index (RI), pulsatility index (PI) and peak systolic velocity (PSV). Ultrasound and coagulation indices were analyzed with matched samples t-test and Wilcoxon rank sum test using the statistical packages in R (version 4.2.1) including car (version 3.1-0) and stats (version 4.2.1), and visualized by ggplot2 package (version 3.3.6). RESULTS: A patient with normal findings in second and third-trimester routine ultrasound scan developed UAT with severe changes in ultrasonic indices of umbilical artery blood flow (within 2.5th of reference ranges) in a short period of time. Statistical analysis of umbilical artery blood flow ultrasound indices for 19 patients with UAT showed that the decrease in S/D, RI, and PI and increase of PSV during the disease process was greater than that of non-UAT. All 18 patients delivered in our hospital showed characteristic manifestations of UAT on histological examination after delivery, most of which (16/18) showed umbilical cord abnormalities, with 15 umbilical cord torsion and 1 pseudoknot. Coagulation parameters were not significantly changed in UAT patients compared with normal pregnancy women. CONCLUSION: Significant changes in ultrasound indicators after UAT were demonstrated. PSV can play important roles in the diagnosis of UAT. Hypercoagulability alone is not sufficient for the occurrence of UAT.

Marginal zone lymphoma with severe rashes: A case report.

BACKGROUND: Marginal zone lymphoma (MZL) is an indolent subtype of non-Hodgkin lymphoma (NHL), which is rare clinically with severe rashes as the initial symptom. CASE SUMMARY: This study reports a case of MZL with generalized skin rashes accompanied by pruritus and purulent discharge. First-line treatment with rituximab combined with zanubrutinib had poor effects. However, after switching to obinutuzumab combined with zanubrutinib, the case was alleviated, and the rashes disappeared. CONCLUSION: For patients with advanced stage MZL not benefiting from type I anti-CD20 monoclonal antibody (mAb) combination therapy, switching to a type II anti-CD20 mAb combination regimen may be considered. This approach may provide a new perspective in the treatment of MZL.

Effects of an explain-simulate-practice-communicate-support intervention on quality of life for patients with chronic heart failure: A randomized control trial.

Background: Patients with New York Heart Association (NYHA) grade III chronic heart failure (CHF) present with low capacity for daily activities, severe self-perceived burden, and poor quality of life. Effective nursing interventions may reduce patients' self-perceived burden and improve their quality of life. Objectives: To explore the effects of an explain-simulate-practice-communicate-support intervention on the self-perceived burden, cardiac function, and activities of daily living (ADL) ability in patients with New York Heart Association grade III chronic heart failure. Methods: Of the 100 patients with New York Heart Association grade III chronic heart failure who were electronically randomized and equally divided into control and intervention groups, data from 88 patients who completed our study were analyzed. The primary outcome was quality of life; secondary outcomes were self-perceived burden, 6-min walking test distances, serum N-terminal pro-brain natriuretic peptide levels, New York Heart Association cardiac function classification, and ability to perform activities of daily living. Results: After 12 weeks' intervention, the intervention group had significantly lower self-perceived burden, Minnesota Living with Heart Failure Questionnaire scores, N-terminal pro-brain natriuretic peptide levels, and New York Heart Association grades compared with the control group, while 6-min walking test distances, left ventricular ejection fraction, and modified Barthel Index scale scores were significantly higher than those in the control group (P > 0.05). Conclusions: The explain-simulate-practice-communicate-support intervention improved patients' quality of life through reducing the level of self-perceived burden, and improving cardiac function and activities of daily living ability. This intervention was found to be effective for patients with New York Heart Association grade III chronic heart failure.

Mechanistic insights into radical formation and functionalization in copper/N-fluorobenzenesulfonimide radical-relay reactions.

Copper-catalysed radical-relay reactions that employ N-fluorobenzenesulfonimide (NFSI) as the oxidant have emerged as highly effective methods for C(sp3)-H functionalization. Herein, computational studies are paired with experimental data to investigate a series of key mechanistic features of these reactions, with a focus on issues related to site-selectivity, enantioselectivity, and C-H substrate scope. (1) The full reaction energetics of enantioselective benzylic C-H cyanation are probed, and an adduct between Cu and the N-sulfonimidyl radical (˙NSI) is implicated as the species that promotes hydrogen-atom transfer (HAT) from the C-H substrate. (2) Benzylic versus 3° C-H site-selectivity is compared with different HAT reagents: Cu/˙NSI, ˙OtBu, and Cl˙, and the data provide insights into the high selectivity for benzylic C-H bonds in Cu/NFSI-catalyzed C-H functionalization reactions. (3) The energetics of three radical functionalization pathways are compared, including radical-polar crossover (RPC) to generate a carbocation intermediate, reductive elimination from a formal CuIII organometallic complex, and radical addition to a Cu-bound ligand. The preferred mechanism is shown to depend on the ligands bound to copper. (4) Finally, the energetics of three different pathways that convert benzylic C-H bonds into benzylic cations are compared, including HAT/ET (ET = electron transfer), relevant to the RPC mechanism with Cu/NFSI; hydride transfer, involved in reactions with high-potential quinones; and sequential ET/PT/ET (PT = proton transfer), involved in catalytic photoredox reactions. Collectively, the results provide mechanistic insights that establish a foundation for further advances in radical-relay C-H functionalization reactions.

Features of the rare pathogen Meyerozyma guilliermondii strain SO and comprehensive in silico analyses of its adherence-contributing virulence factor agglutinin-like sequences.

Meyerozyma guilliermondii is a rare yeast pathogen contributing to the deadly invasive candidiasis. M. guilliermondii strain SO, as a promising protein expression host, showed 99% proteome similarity with the clinically isolated ATCC 6260 (type strain) in a recent comparative genomic analysis. However, their in vitro virulence features and in vivo pathogenicity were uncharacterized. This study aimed to characterize the in vitro and in vivo pathogenicity of M. guilliermondii strain SO and analyze its Als proteins (MgAls) via comprehensive bioinformatics approaches. M. guilliermondii strain SO showed lower and higher sensitivity towards ß-mercaptoethanol and lithium, respectively than the avirulent S. cerevisiae but exhibited the same tolerance towards cell wall-perturbing Congo Red with C. albicans. With 7.5× higher biofilm mass, M. guilliermondii strain SO also demonstrated 75% higher mortality rate in the zebrafish embryos with a thicker biofilm layer on the chorion compared to the avirulent S. cerevisiae. Being one of the most important Candida adhesins, sequence and structural analyses of four statistically identified MgAls showed that MgAls1056 was predicted to exhibit the most conserved amyloid-forming regions, tandem repeat domain and peptide binding cavity (PBC) compared to C. albicans Als3. Favoured from the predicted largest ligand binding site and druggable pockets, it showed the highest affinity towards hepta-threonine. Non-PBC druggable pockets in the most potent virulence contributing MgAls1056 provide new insights into developing antifungal drugs targeting non-albicans Candida spp. Virtual screening of available synthetic or natural bioactive compounds and MgAls1056 deletion from the fungal genome should be further performed and validated experimentally.Communicated by Ramaswamy H. Sarma.

Multifunctional Interlayer Engineering for Silkworm Excrement-Derived Porous Carbon Enabling High-Energy Lithium Sulfur Batteries.

Lithium-sulfur (Li-S) batteries show advantage of high theoretical capacity. However, the shuttle effect of polysulfides and sluggish sulfur redox kinetics seriously reduce their service life. Inspired by the porous structural features of biomass materials, herein, a functional interlayer is fabricated by silkworm excrement-derived three-dimensional porous carbon accommodating nano sized CoS2 particles (SC@CoS2 ). The porous carbon delivers a high specific surface area, which provides adequate adsorption sites, being responsible for suppressing the shuttle effect of polysulfides. Meanwhile, the porous carbon is favorable for hindering the aggregation of CoS2 and maintaining its high activity during extended cycles, which effectively accelerates the polysulfides conversion kinetics. Moreover, the SC@CoS2 functional interlayer effectively limits the formation of Li dendrites and promotes the uniform deposition of Li on the Li electrode surface. As a result, the CMK-3/S cathode achieves a high initial capacity of 1599.1 mAh g-1 at 0.2 C rate assisted by the polypropylene separator coated with the functional interlayer and 1208.3 mAh g-1 is maintained after the long cycling test. This work provides an insight into the designing of long-lasting catalysts for stable functional interlayer, which encourages the application of biomass-derived porous carbon in high-energy Li-S batteries.