Different fates of Sb(III) and Sb(V) during the formation of jarosite mediated by Acidithiobacillus ferrooxidans.

Secondary iron-sulfate minerals such as jarosite, which are easily formed in acid mine drainage, play an important role in controlling metal mobility. In this work, the typical iron-oxidizing bacterium Acidithiobacillus ferrooxidans ATCC 23270 was selected to synthesize jarosite in the presence of antimony ions, during which the solution behavior, synthetic product composition, and bacterial metabolism were studied. The results show that in the presence of Sb(V), Fe2+ was rapidly oxidized to Fe3+ by A. ferrooxidans and Sb(V) had no obvious effect on the biooxidation of Fe2+ under the current experimental conditions. The presence of Sb(III) inhibited bacterial growth and Fe2+ oxidation. For the group with Sb(III), products with amorphous phases were formed 72 hr later, which were mainly ferrous sulfate and pentavalent antimony oxide, and the amorphous precursor was finally transformed into a more stable crystal phase. For the group with Sb(V), the morphology and structure of jarosite were changed in comparison with those without Sb. The biomineralization process was accompanied by the removal of 94% Sb(V) to form jarosite containing the Fe-Sb-O complex. Comparative transcriptome analysis shows differential effects of Sb(III) and Sb(V) on bacterial metabolism. The expression levels of functional genes related to cell components were much more downregulated for the group with Sb(III) but much more regulated for that with Sb(V). Notably, cytochrome c and nitrogen fixation-relevant genes for the A.f_Fe2+_Sb(III) group were enhanced significantly, indicating their role in Sb(III) resistance. This study is of great value for the development of antimony pollution control and remediation technology.

Impact of Diabetes on Persistent Radiological Abnormalities and Pulmonary Diffusion Dysfunction in COVID-19 Survivors: A 3-Year Prospective Cohort Study.

RATIONALE AND OBJECTIVES: Little is known about the long-term impact of diabetes on lung impairment in COVID-19 survivors over a three-year period. This study evaluated the long-term impact of diabetes on persistent radiological pulmonary abnormalities and lung function impairment in COVID-19 survivors over three years. MATERIALS AND METHODS: In this prospective, multicenter, cohort study, pulmonary sequelae were compared between COVID-19 survivors with and without diabetes. Serial chest CT scans, symptom questionnaires and pulmonary function tests were obtained 6 months, 12 months, 2 years and 3 years post-discharge. The independent predictors for lung dysfunction at the 3-year follow-up were analyzed. RESULTS: A total of 278 COVID-19 survivors (63 [IQR 57-69] year-old, female: 103 [37.0%]) were included. At the 3-year follow-up, individuals in the diabetes group had higher incidences of respiratory symptoms, radiological pulmonary abnormalities and pulmonary diffusion dysfunction than those in the control group. Diabetes (OR: 2.18, 95% CI: 1.04-4.59, p = 0.034), allergy (OR: 2.26, 95% CI: 1.09-4.74, p = 0.029), female (OR: 2.70, 95% CI: 1.37-5.29, p = 0.004), severe COVID-19 (OR: 4.10, 95% CI: 1.54-10.93, p = 0.005), and fibrotic-like CT changes (OR: 5.64, 95% CI: 2.28-13.98, p < 0.001) were independent predictors of pulmonary diffusion dysfunction in COVID-19 survivors. CONCLUSION: These results highlight the long-term deleterious effect of diabetes status on radiological pulmonary abnormalities and pulmonary dysfunction in COVID-19 survivors. This study provides important evidence support for long-term monitoring of lung abnormalities in COVID-19 recovery survivors with diabetes.

Discovery of Novel Nonpeptidic and Noncovalent Small Molecule 3CLpro Inhibitors as anti-SARS-CoV-2 Drug Candidate.

SARS-CoV-2 has still been threatening global public health with its emerging variants. Our previous work reported lead compound JZD-07 that displayed good 3CLpro inhibitory activity. Here, an in-depth structural optimization for JZD-07 was launched to obtain more desirable drug candidates for the therapy of SARS-CoV-2 infection, in which 54 novel derivatives were designed and synthesized by a structure-based drug design strategy. Among them, 24 compounds show significantly enhanced 3CLpro inhibitory potencies with IC50 values less than 100 nM, and 11 compounds dose-dependently inhibit the replication of the SARS-CoV-2 delta variant. In particular, compound 49 has the most desirable antiviral activity with EC50 of 0.272 ± 0.013 µM against the delta variant, which was more than 20 times stronger than JZD-07. Oral administration of 49 could significantly reduce the lung viral copies of mice, exhibiting a more favorable therapeutic potential. Overall, this investigation presents a promising drug candidate for further development to treat SARS-CoV-2 infection.

Brentuximab vedotin plus cyclophosphamide, doxorubicin, etoposide, and prednisone followed by brentuximab vedotin consolidation in CD30-positive peripheral T-cell lymphomas: a multicentre, single-arm, phase 2 study.

BACKGROUND: CD30 expression is universal in anaplastic large-cell lymphoma and is expressed in some other peripheral T-cell lymphoma subtypes. Incorporation of brentuximab vedotin into initial therapy for people with CD30-positive peripheral T-cell lymphomas prolonged progression-free survival, but there is room for improvement, especially for people with non-anaplastic large-cell lymphoma subtypes. METHODS: We conducted a multicentre, international, single-arm, phase 2 trial to evaluate the safety and activity of CHEP-BV (cyclophosphamide, doxorubicin, prednisone, brentuximab vedotin, and etoposide) followed by brentuximab vedotin consolidation in patients with CD30-expressing peripheral T-cell lymphomas across five academic centres in the USA and Canada. Adults aged 18 years or older with newly diagnosed, untreated CD30-positive peripheral T-cell lymphomas, Eastern Cooperative Oncology Group score of 0-2, and adequate organ function were eligible to receive six planned cycles of CHEP-BV (ie, 1·8 mg/kg brentuximab vedotin intravenously on day 1, cyclophosphamide 750 mg/m2 intravenously on day 1, doxorubicin 50 mg/m2 intravenously on day 1, etoposide 100 mg/m2 daily intravenously on days 1-3, and prednisone 100 mg daily orally on days 1-5) with prophylactic G-CSF. Patients who responded to the treatment could receive brentuximab vedotin consolidation for up to ten additional cycles either after autologous haematopoietic stem-cell transplantation (HSCT) or directly after CHEP-BV. The primary endpoints were unacceptable toxicity during a 3-plus-3 safety lead-in in participants who received study treatment and completed the safety evaluation period (to confirm the recommended phase 2 dose of brentuximab vedotin in CHEP-BV) and the complete response rate after CHEP-BV induction therapy in participants who received study treatment and had response evaluation. The study was registered at ClinicalTrials.gov (NCT03113500), and this cohort completed the trial. The trial is ongoing with the enrolment of a new cohort. FINDINGS: 54 patients were screened for eligibility and 48 were eligible for the study. The participants (18 [38%] women and 30 [63%] men; 34 [71%] White, four [8%] Black, five [10%] Asian, ten [21%] Hispanic, and 37 [77%] non-Hispanic people) were recruited and enrolled between Dec 4, 2017, and June 14, 2021, and followed up until Aug 25, 2023, when the database was locked for analysis. 48 participants were evaluable for toxicity, and 47 were evaluable for response (one participant died from COVID-19 before response assessment). During the safety lead-in, one of six participants had an unacceptable toxicity (ie, platelet count <10 000 per mm3 in a participant with extensive bone marrow involvement), and the proposed phase 2 dose of 1·8 mg/kg brentuximab vedotin in CHEP-BV was confirmed. At completion of CHEP-BV, 37 of 47 participants had complete response, yielding a complete response rate of 79% (95% CI 64-89). The most common CHEP-BV-related toxicities of grade 3 or higher were neutropenia (14 [29%] of 48), leukopenia (11 [23%]), anaemia (ten [21%]), febrile neutropenia (ten [21%]), lymphopenia (nine [19%]), and thrombocytopenia (nine [19%]). There were no treatment-related deaths. INTERPRETATION: In patients with mostly CD30-expressing peripheral T-cell lymphomas other than non-anaplastic large-cell lymphoma, CHEP-BV (with or without autologous HSCT) followed by brentuximab vedotin consolidation was safe and active. FUNDING: SeaGen, Leukemia and Lymphoma Society, Lymphoma Research Foundation, and the National Cancer Institute of the National Institutes of Health.

Epigallocatechin-3-gallate attenuates fluoride induced apoptosis via PI3K/FoxO1 pathway in ameloblast-like cells.

Fluoride is a double-edged sword. It was widely used for early caries prevention while excessive intake caused a toxicology effect, affected enamel development, and resulted in dental fluorosis. The study aimed to evaluate the protective effect and mechanism of Epigallocatechin-3-gallate (EGCG) on the apoptosis induced by fluoride in ameloblast-like cells. We observed that NaF triggered apoptotic alterations in cell morphology, excessive NaF arrested cell cycle at the G1, and induced apoptosis by up-regulating Bax and down-regulating Bcl-2. NaF activated the insulin-like growth factor receptor (IGFR), and phosphatidylinositol-3-hydroxylase (p-PI3K), while dose-dependently down-regulating the expression of Forkhead box O1 (FoxO1). EGCG supplements reversed the changes in LS8 morphology, the cell cycle, and apoptosis induced by fluoride. These results indicated that EGCG possesses a protective effect against fluoride toxicity. Furthermore, EGCG suppressed the activation of p-PI3K and the down-regulation of FoxO1 caused by fluoride. Collectively, our findings suggested that EGCG attenuated fluoride-induced apoptosis by inhibiting the PI3K/FoxO1 signaling pathway. EGCG may serve as a new alternative method for dental fluorosis prevention, control, and treatment.

Reliability and validity study of the Chinese version of the Cerebellar Cognitive Affective Syndrome Scale in patients with cerebellar injury.

PURPOSE: To preliminarily investigate the reliability and validity of the Chinese version of the Cerebellar Cognitive Affective Syndrome Scale (CCAS scale) in the cerebellar injury population. METHODS: In this study, 40 patients with cerebellar injury and 39 normal individuals hospitalized in a stroke center were assessed using the Chinese version of the CCAS scale A, MMSE, and PHQ2, and the results were analyzed using content validity, structural validity, internal consistency, inter- rater agreement, and test-retest reliability. RESULTS: The correlation coefficients of semantic fluency, phonemic fluency, category switching, digit span forward, digit span backward, cube, verbal recall, similarities and Go No-Go subscores in the Chinese version of the CCAS scale A were 0.586-0.831 (P ≤ 0.05) with the total score, but there was no significant correlation between the affect and the total score (P = 0.110). The total cognitive score of the Chinese version of the CCAS scale A was correlated with the (r = 0.807, P ≤ 0.01), and the total score of the Chinese version of the CCAS scale A affect was correlated with the total score of PHQ2 (r = 0.884, P ≤ 0.01). The 2 factors were extracted using principal component analysis, and the cumulative variance contribution rate was 59.633%. The factor loadings of each of the corresponding factors were > 0.5, indicating good structural validity of the Chinese version of the CCAS scale A. Cronbach α = 0.827 indicated good internal consistency, and inter-rater reliability (ICC > 0.95) and test-retest reliability (ICC = 0.717-0.895)indicated that the Chinese version of the CCAS scale A had good inter-rater reliability and test-retest reliability. CONCLUSION: The Chinese version of the CCAS scale A has good reliability and validity in the cerebellar injury population and is useful for screening cerebellar cognitive-emotional syndrome.

Validation of the Center for Neurologic Study Bulbar Function Scale-Chinese version in a population with amyotrophic lateral sclerosis.

OBJECTIVE: The Center for Neurologic Study Bulbar Function Scale (CNS-BFS) was specifically designed as a self-reported measure of bulbar function. The purpose of this research was to validate the Chinese translation of the CNS-BFSC as an effective measurement for the Chinese population with ALS. METHODS: A total of 111 ALS patients were included in this study. The CNS-BFSC score, three bulbar function items from the ALSFRS-R, and visual analog scale (VAS) score for speech, swallowing and salivation were assessed in the present study. Forty-six ALS patients were retested on the same scale 5-10 days after the first evaluation. RESULTS: The CNS-BFSC sialorrhea, speech and swallowing subscores were separately correlated with the VAS subscores (p < 0.001). The CNS-BFSC total score and sialorrhea and speech scores were significantly correlated with the ALSFRS-R bulbar subscore (p < 0.001). The CNS-BFSC total score and ALSFRS-R bulbar subscale score were highly predictive of a clinician diagnosis of impaired bulbar function (area under the receiver operating characteristic curve, 0.947 and 0.911, respectively; p < 0.001). A cutoff value for the CNS-BFSC total score was selected by maximizing Youden's index; this cutoff score was 33, with 86.4% sensitivity and 93.3% specificity. The CNS-BFSC total score and the sialorrhea, speech and swallowing subscores had good-retest reliability (p > 0.05). The Cronbach's α of the CNS-BFSC was 0.972. CONCLUSION: The Chinese version of the CNS-BFSC has acceptable efficacy and reliability for the assessment of bulbar dysfunction in ALS patients.

Asthma and risk of adverse pregnancy outcomes: A Mendelian randomization study.

Background: Multiple empirical investigations have indicated a connection between asthma and adverse pregnancy outcomes (APOs). Nevertheless, the effects of asthma on APOs remain uncertain. Methods: We performed bi-directional Univariable Mendelian randomization (UVMR) analyses using combined information obtained from genome-wide association studies (GWAS) data that is publicly accessible. The principal approach used to analyze the causal association between asthma or age when diagnosed and APOs was the inverse variance weighted (IVW) method. The two types of data regarding exposure originate from the IEU Open GWAS project, which includes 56,167 and 47,222 European asthma patients, respectively. The data of four APOs were acquired via the GWAS dataset of the FinnGen collaboration. In addition, we implemented multivariable Mendelian randomization (MVMR), controlling for confounding factors such as smoking status, frequent drinking, body mass index (BMI), and live birth quantity. Furthermore, we executed several meticulous sensitivity studies to ascertain the reliability of our MR results. Results: Following the implementation of the Bonferroni adjustment, the UVMR assessment revealed that in the IVW model, asthma was significantly linked to an elevated risk of spontaneous abortion (SA) (odds ratio [OR]: 1.115; 95 % confidence interval [CI]: 1.031-1.206; P = 0.006) and gestational diabetes mellitus (GDM) (OR: 1.125; 95 % CI: 1.037-1.220; P = 0.005). However, there was no causal correlation between asthma and preterm birth (PTB) (OR: 0.979; 95 % CI: 0.897-1.068; P = 0.629) or preeclampsia (PE) (OR: 1.059; 95 % CI: 0.951-1.179; P = 0.297). After adjusting for confounding factors, including smoking status, frequent drinking, BMI, and live birth quantity, the MVMR analysis shows a statistically significant causal relationship between asthma and SA or GDM. Furthermore, our investigation's findings did not reveal a substantial correlation between the age of asthma onset based on genetics and the likelihood of SA or GDM. The inverse MR outcomes indicate a lack of causal connection linking APOs to the incidence of asthma. The validity of these findings were verified by sensitivity analyses. Conclusions: The evidence provided by this study proves that genetically determined asthma is linked to a higher likelihood of SA and GDM. Further research is required to examine potential pathways. However, no conclusive evidence has been found to support the increased risk of SA and GDM in early asthma diagnosis or the interaction between asthma and PTB or PE, indicating that confounding factors may affect the results of previous observational studies.

Intact painful sensation but enhanced non-painful sensation in individuals with autistic traits.

Somatosensory abnormalities are commonly recognized as diagnostic criteria in autism spectrum disorder (ASD), and may also exist in individuals with autistic traits. The present research included two studies to explore the painful and non-painful sensation and their cognitive-neurological mechanisms of individuals with autistic traits. Study 1 included 358 participants to assess the relationship between autistic traits and pain/non-pain sensitivities using questionnaires: the Autism Spectrum Quotient (AQ), the Pain Sensitivity Questionnaire, and the Highly Sensitive Person Scale, respectively. Study 1 found that autistic traits were positively correlated with non-pain sensitivity, but not associated with pain sensitivity. Study 2 recruited 1,167 participants whose autistic traits were assessed using the AQ. Subsequently, thirty-three participants who scored within the top 10% and bottom 10% on the AQ were selected into High-AQ and Low-AQ groups, respectively, to explore the cognitive-neural responses of individuals with autistic traits to both painful and non-painful stimuli with event-related potential (ERP) technology. Results of Study 2 showed that the High-AQ group showed higher intensity ratings, more negative emotional reactions, and larger N1 amplitudes than the Low-AQ group to the non-painful stimuli, but no difference of response to the painful stimuli was found between High-AQ and Low-AQ groups. These findings suggest that individuals with autistic traits may experience enhanced non-painful sensation but intact painful sensation.

Waveform Design for the Integrated Sensing, Communication, and Simultaneous Wireless Information and Power Transfer System.

Next-generation communication systems demand the integration of sensing, communication, and power transfer (PT) capabilities, requiring high spectral efficiency, energy efficiency, and low cost while also necessitating robustness in high-speed scenarios. Integrated sensing and communication systems (ISACSs) exhibit the ability to simultaneously perform communication and sensing tasks using a single RF signal, while simultaneous wireless information and power transfer (SWIPT) systems can handle simultaneous information and energy transmission, and orthogonal time frequency space (OTFS) signals are adept at handling high Doppler scenarios. Combining the advantages of these three technologies, a novel cyclic prefix (CP) OTFS-based integrated simultaneous wireless sensing, communication, and power transfer system (ISWSCPTS) framework is proposed in this work. Within the ISWSCPTS, the CP-OTFS matched filter (MF)-based target detection and parameter estimation (MF-TDaPE) algorithm is proposed to endow the system with sensing capabilities. To enhance the system's sensing capability, a waveform design algorithm based on CP-OTFS ambiguity function shaping (AFS) is proposed, which is solved by an iterative method. Furthermore, to maximize the system's sensing performance under communication and PT quality of service (QoS) constraints, a semidefinite relaxation (SDR) beamforming design (SDR-BD) algorithm is proposed, which is solved using through the SDR technique. The simulation results demonstrate that the ISWSCPTS exhibits stronger parameter estimation performance in high-speed scenarios compared to orthogonal frequency division multiplexing (OFDM), the waveform designed by CP-OTFS AFS demonstrates superior interference resilience, and the beamforming designed by SDR-BD strikes a balance in the overall performance of the ISWSCPTS.

Subsurface Single-atom Catalyst Enabled by Mechanochemical Synthesis for Oxidation Chemistry.

Single-atom catalysts have garnered significant attention due to their exceptional atom utilization and unique properties. However, the practical application of these catalysts is often impeded by challenges such as sintering-induced instability and poisoning of isolated atoms due to strong gas adsorption. In this study, we employed the mechanochemical method to insert single Cu atoms into the subsurface of Fe2O3 support. By manipulating the location of single atoms at the surface or subsurface, catalysts with distinct adsorption properties and reaction mechanisms can be achieved. It was observed that the subsurface Cu single atoms in Fe2O3 remained isolated under both oxidation and reduction environments, whereas surface Cu single atoms on Fe2O3 experienced sintering under reduction conditions. The unique properties of these subsurface single-atom catalysts call for innovations and new understandings in catalyst design.

Design, synthesis, pharmacological evaluation, and computational study of benzo[d] isothiazol-based small molecule inhibitors targeting PD-1/PD-l1 interaction.

Blockade of the programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway is an attractive strategy for immunotherapy, but the clinical application of small molecule PD-1/PD-L1 inhibitors remains unclear. In this work, based on BMS-202 and our previous work YLW-106, a series of compounds with benzo[d]isothiazol structure as scaffold were designed and synthesized. Their inhibitory activity against PD-1/PD-L1 interaction was evaluated by a homogeneous time-resolved fluorescence (HTRF) assay. Among them, LLW-018 (27c) exhibited the most potent inhibitory activity with an IC50 value of 2.61 nM. The cellular level assays demonstrated that LLW-018 exhibited low cytotoxicity against Jurkat T and MDA-MB-231. Further cell-based PD-1/PD-L1 blockade bioassays based on PD-1 NFAT-Luc Jurkat cells and PD-L1 TCR Activator CHO cells indicated that LLW-018 could interrupt PD-1/PD-L1 interaction with an IC50 value of 0.88 µM. Multi-computational methods, including molecular docking, molecular dynamics, MM/GBSA, MM/PBSA, Metadynamics, and QM/MM MD were utilized on PD-L1 dimer complexes, which revealed the binding modes and dissociation process of LLW-018 and C2-symmetric small molecule inhibitor LCH1307. These results suggested that LLW-018 exhibited promising potency as a PD-1/PD-L1 inhibitor for further investigation.

A Mitochondria-Targeted Photosensitizer for Combined Pyroptosis and Apoptosis with NIR-II Fluorescence/Photoacoustic Imaging-Guided Phototherapy.

Overcoming tumor apoptosis resistance is a major challenge in enhancing cancer therapy. Pyroptosis, a lytic form of programmed cell death (PCD) involving inflammasomes, Gasdermin family proteins, and cysteine proteases, offers potential in cancer treatment. While photodynamic therapy (PDT) can induce pyroptosis by generating reactive oxygen species (ROS) through the activation of photosensitizers (PSs), many PSs lack specific subcellular targets and are limited to the first near-infrared window, potentially reducing treatment effectiveness. Therefore, developing effective, deep-penetrating, organelle-targeted pyroptosis-mediated phototherapy is essential for cancer treatment strategies. Here, we synthesized four molecules with varying benzene ring numbers in thiopyrylium structures to preliminarily explore their photodynamic properties. The near-infrared-II (NIR-II) PS Z1, with a higher benzene ring count, exhibited superior ROS generation and mitochondria-targeting abilities, and a large Stokes shift. Through nano-precipitation method, Z1 nanoparticles (NPs) also demonstrated high ROS generation (especially type-I ROS) upon 808 nm laser irradiation, leading to efficient mitochondria dysfunction and combined pyroptosis and apoptosis. Moreover, they exhibited exceptional tumor-targeting ability via NIR-II fluorescence imaging (NIR-II FI) and photoacoustic imaging (PAI). Furthermore, Z1 NPs-mediated phototherapy effectively inhibited tumor growth with minimal adverse effects. Our findings offer a promising strategy for cancer therapy, warranting further preclinical investigations in PDT.

Psychological Status and Warfarin Therapy in Patients after Valve Replacement during the COVID-19 Pandemic: A Cross-sectional Study.

OBJECTIVE: The standardization of warfarin anticoagulant therapy is the key to lifelong treatment for patients after heart valve replacement. The present study explored the possible risk factors for anxiety and depression during the coronavirus disease 2019 (COVID-19) pandemic and analyzed the influence of psychological state on medication safety. METHODS: Eligible patients received a web-based questionnaire survey via the Wenjuanxing platform during outpatient visits. Depression was evaluated by the Self-Rating Depression Scale (SDS). Anxiety was evaluated by the Self-Rating Anxiety Scale (SAS). Medication adherence was evaluated by the Morisky scale. RESULTS: A total of 309 patients (aged 52.2±11.4 years) were included in the present study. The SDS score of all included patients was 36.9±9.4 points, of which 11 (3.6%) patients were diagnosed as having depression. The SAS score of all included patients was 43.1±9.3 points, of which 71 (23%) patients were diagnosed as having anxiety. Seven patients (2.3%) had both anxiety and depression. Logistic regression analysis revealed that only monthly income was an independent influencing factor for depression. Regarding anxiety, patients who underwent repeated operations had a 2.264-fold greater risk, and patients who received combination medication had a 2.140-fold greater risk. More bleeding events and coagulation disorders could be observed in patients with anxiety, depression or both. When anxiety occurred, patients showed worse medication adherence. However, depression had no significant effect on medication adherence. CONCLUSION: During the COVID-19 pandemic, the detection rate of mental illnesses such as anxiety and depression was high, which seriously affected the medication safety of warfarin. Analysis of its influencing factors will provide a reference for further standardized regulation of warfarin anticoagulant therapy after valve replacement.

Chloroplast genome of plantago major, a medicinal plant in China.

Plantago major (Plantaginaceae) is a medicinal plant in Chinese folk culture, known for its famous medicinal components such as plantagomain. In this study, we conducted genome sequencing of P. major using Illumina sequencing technology. The assembled complete chloroplast genome had a length of 165,044 bp, comprising a large single-copy regions (82,963 bp), a small single-copy regions (4,633 bp), and a pair of inverted repeat regions (38,724 bp). A total of 140 genes were detected, including 94 CDS, 38 tRNA, and 8 rRNA. Phylogenetic analysis revealed a close genetic relationship between P. major and P. rigida. These findings provide valuable data for a comprehensive understanding of the biological characteristics of P. major.

Effects of systematic cardiac rehabilitation training in elderly patients with unstable angina following cardiac stent implantation.

BACKGROUND: Coronary stent implantation is usually used to treat unstable angina to alleviate stenosis or occlusion, promoting blood flow restoration and alleviating symptoms such as myocardial ischemia. And postoperative cardiac rehabilitation is essential for enhancing recovery and prognosis. Nevertheless, conventional rehabilitation lacks specificity, particularly for elderly patients with multiple comorbidities and poor compliance, rendering it less effective. AIM: To investigate the effects of systematic cardiac rehabilitation training in elderly patients with unstable angina following coronary stenting intervention. METHODS: A retrospective enrollment was conducted comprising fifty-four elderly patients with unstable angina pectoris who underwent systematic cardiac rehabilitation training after receiving coronary intervention as the rehabilitation group, while fifty-three elderly patients who received basic nursing and rehabilitation guidance measures after coronary intervention were assigned to the control group. Differences in Seattle Angina Questionnaire scores, survival quality (SF-36) scores, cardiopulmonary exercise function assessment index, echocardiographic cardiac function index, and adverse cardiovascular events were compared between the two groups. RESULTS: After intervention, the rehabilitation group observed greater VO2 Max, maximum metabolic equivalent, eft ventricular ejection fraction, left ventricular end-diastolic diameter and smaller left ventricular end-systolic diameter. And the rehabilitation group observed greater scores of physical activity limitation, stable angina pectoris, treatment satisfaction, and SF-36 score. The incidence of adverse cardiovascular events in the two groups, showed no significant difference. CONCLUSION: Systematic cardiac rehabilitation following coronary stenting in elderly patients with unstable angina pectoris can enhance cardiac function recovery, consequently enhancing both quality of life and cardiopulmonary exercise tolerance.

Clonal inactivation of TERT impairs stem cell competition.

Telomerase is intimately associated with stem cells and cancer, because it catalytically elongates telomeres-nucleoprotein caps that protect chromosome ends1. Overexpression of telomerase reverse transcriptase (TERT) enhances the proliferation of cells in a telomere-independent manner2-8, but so far, loss-of-function studies have provided no evidence that TERT has a direct role in stem cell function. In many tissues, homeostasis is shaped by stem cell competition, a process in which stem cells compete on the basis of inherent fitness. Here we show that conditional deletion of Tert in the spermatogonial stem cell (SSC)-containing population in mice markedly impairs competitive clone formation. Using lineage tracing from the Tert locus, we find that TERT-expressing SSCs yield long-lived clones, but that clonal inactivation of TERT promotes stem cell differentiation and a genome-wide reduction in open chromatin. This role for TERT in competitive clone formation occurs independently of both its reverse transcriptase activity and the canonical telomerase complex. Inactivation of TERT causes reduced activity of the MYC oncogene, and transgenic expression of MYC in the TERT-deleted pool of SSCs efficiently rescues clone formation. Together, these data reveal a catalytic-activity-independent requirement for TERT in enhancing stem cell competition, uncover a genetic connection between TERT and MYC and suggest that a selective advantage for stem cells with high levels of TERT contributes to telomere elongation in the male germline during homeostasis and ageing.

Specific immunological characteristics and risk factor of XBB variants re-infection in nasopharyngeal carcinoma patients after BA.5 infection.

OBJECTIVES: The specific humoral immune response resulting from inactivated vaccination following by BA.5 infection, and predictors of XBB variants re-infection in BA.5 infection-recovered nasopharyngeal carcinoma (BA.5-RNPC) patients, were explored. METHODS: Serum SARS-CoV-2 specific antibody levels were assessed using enzyme-linked-immunosorbent-assay. Univariate and multivariate binary logistic regression analyses were conducted to identify factors associated with the magnitude of specific humoral immunity and susceptibility to re-infection by XBB variants. RESULTS: Our data demonstrates that SARS-CoV-2 specific antibody levels were comparable between BA.5-RNPC patients and BA.5 infection-recovered-non-cancerous (BA.5-RNC) individuals. Specifically, serum levels of anti-ancestral-S1-IgG, anti-ancestral-nucleocapsid-protein (NP)-IgG, anti-BA.5-receptor binding domain (RBD)-IgG and anti-XBB.1.1.6-RBD-IgG were higher in BA.5-RNPC patients compared to those without a prior infection. Compared to BA.5-RNPC patients without vaccination, individuals who received inactivated vaccination exhibited significantly higher levels of anti-ancestral-S1-IgG and anti-XBB.1.16-RBD-IgG. Multivariate logistic regression analysis revealed that inactivated vaccination was the most significant predictor of all tested SARS-CoV-2 specific antibodies response. Subsequent analysis indicated that a low globulin level is an independent risk factor for XBB re-infection in BA.5-RNPC patients. CONCLUSIONS: The SARS-CoV-2 specific antibodies have been improved in vaccinated BA.5-RNPC patients. However, the baseline immunity status biomarker IgG is an indicators of XBB variant re-infection risk in BA.5-RNPC patients.

Determination of eleven components in rat plasma by UPLC-MS/MS and GC-MS for pharmacokinetic studies after oral administration of Citri Reticulatae Pericarpium extract.

Citri Reticulatae Pericarpium (CRP) is used as common health-care food and traditional Chinese medicine (TCM), which exerts pharmacological effects, such as anti-cardiovascular, anti-tumor, anti-oxidant, anti-inflammatory, anti-virus, hepatoprotective, blood pressure-lowering and neuroprotective. In this study, reliable, and sensitive ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) methods were developed and validated for the determination of eleven active components in rat plasma after oral administration of the CRP extract. The results of this method exhibited that the specificity, linearity (r > 0.999), precision and accuracy (the coefficient of variation (CV) < 11.5 %), recovery (52.9-107.9 %), matrix effects (63.8-107.5 %), and stability (CV < 10.8 %) met all requirements for the quantitation of plasma samples. The pharmacokinetic results showed that the Tmax of flavone glycosides was less than 0.7 h, and that of polymethoxyflavones and volatile components were within 1-7 h. Meanwhile, the area-under-the-curve (AUC) and concentration maximum (Cmax) of hesperidin, nobiletin, tangeretin, and D-limonene were higher than those of the other components, suggesting that the plasma exposure levels of these constituents were higher in CRP. The present research lays a foundation for elucidating the therapeutic material basis and provides a reference for further scientific research and clinical application of CRP.

Oxygenate-induced structural evolution of high-entropy electrocatalysts for multifunctional alcohol electrooxidation integrated with hydrogen production.

High-entropy compounds have been emerging as promising candidates for electrolysis, yet their controllable electrosynthesis strategy remains a formidable challenge because of the ambiguous ionic interaction and codeposition mechanism. Herein, we report a oxygenates directionally induced electrodeposition strategy to construct high-entropy materials with amorphous features, on which the structural evolution from high-entropy phosphide to oxide is confirmed by introducing vanadate, thus realizing the simultaneous optimization of composition and structure. The representative P-CoNiMnWVOx shows excellent bifunctional catalytic performance toward alkaline hydrogen evolution reaction and ethanol oxidation reaction (EOR), with small potentials of -168 mV and 1.38 V at 100 mA cm-2, respectively. In situ spectroscopy illustrates that the electrochemical reconstruction of P-CoNiMnWVOx induces abundant Co-O species as the main catalytic active species for EOR and follows the conversion pathway of the C2 product. Theoretical calculations reveal the optimized electronic structure and adsorption free energy of reaction intermediates on P-CoNiMnWVOx, thereby resulting in a facilitated kinetic process. A membrane-free electrolyzer delivers both high Faradaic efficiencies of acetate and H2 over 95% and superior stability at100 mA cm-2 during 120 h electrolysis. In addition, the unique composition and structural advantages endow P-CoNiMnWVOx with multifunctional catalytic activity and realize multipathway electrosynthesis of formate-coupled hydrogen production.