Therapeutic implications of quercetin and its derived-products in COVID-19 protection and prophylactic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel human coronavirus, which has triggered a global pandemic of the coronavirus infectious disease 2019 (COVID-19). Outbreaks of emerging infectious diseases continue to challenge human health worldwide. The virus conquers human cells through the angiotensin-converting enzyme 2 receptor-driven pathway by mostly targeting the human respiratory tract. Quercetin is a natural flavonoid widely represented in the plant kingdom. Cumulative evidence has demonstrated that quercetin and its derivatives have various pharmacological properties including anti-cancer, anti-hypertension, anti-hyperlipidemia, anti-hyperglycemia, anti-microbial, antiviral, neuroprotective, and cardio-protective effects, because it is a potential treatment for severe inflammation and acute respiratory distress syndrome. Furthermore, it is the main life-threatening condition in patients with COVID-19. This article provides a comprehensive review of the primary literature on the predictable effectiveness of quercetin and its derivatives docked to multi-target of SARS-CoV-2 and host cells via in silico and some of validation through in vitro, in vivo, and clinically to fight SARS-CoV-2 infections, contribute to the reduction of inflammation, which suggests the preventive and therapeutic latency of quercetin and its derived-products against COVID-19 pandemic, multisystem inflammatory syndromes (MIS), and long-COVID.

A Lateral Flow-Recombinase Polymerase Amplification Method for Colletotrichum gloeosporioides Detection.

The greater yam (Dioscorea alata), a widely cultivated and nutritious food crop, suffers from widespread yield reduction due to anthracnose caused by Colletotrichum gloeosporioides. Latent infection often occurs before anthracnose phenotypes can be detected, making early prevention difficult and causing significant harm to agricultural production. Through comparative genomic analysis of 60 genomes of 38 species from the Colletotrichum genus, this study identified 17 orthologous gene groups (orthogroups) that were shared by all investigated C. gloeosporioides strains but absent from all other Colletotrichum species. Four of the 17 C. gloeosporioides-specific orthogroups were used as molecular markers for PCR primer designation and C. gloeosporioides detection. All of them can specifically detect C. gloeosporioides out of microbes within and beyond the Colletotrichum genus with different sensitivities. To establish a rapid, portable, and operable anthracnose diagnostic method suitable for field use, specific recombinase polymerase amplification (RPA) primer probe combinations were designed, and a lateral flow (LF)-RPA detection kit for C. gloeosporioides was developed, with the sensitivity reaching the picogram (pg) level. In conclusion, this study identified C. gloeosporioides-specific molecular markers and developed an efficient method for C. gloeosporioides detection, which can be applied to the prevention and control of yam anthracnose as well as anthracnose caused by C. gloeosporioides in other crops. The strategy adopted by this study also serves as a reference for the identification of molecular markers and diagnosis of other plant pathogens.

Histology and transcriptomic analysis reveal the inflammation and affected pathways under 2-methylisoborneol (2-MIB) exposure on grass carp.

2-Methylisoborneol (2-MIB) is a common and widely distributed off-flavor compound in water. However, the toxic mechanisms of 2-MIB on aquatic organisms remain largely unexplored. In this study, grass carp larvae were exposed to different concentrations (0, 5, and 20 µg L-1) of 2-MIB for 96 h. The accumulation of 2-MIB in the dorsal muscle was measured. Histological analysis, ultrastructure observations, and transcriptomic sequencing were conducted on the liver tissues. The results showed that 2-MIB accumulated significantly in the fish muscle, with the accumulation increasing as the exposure concentration increased through gas chromatography-mass spectrometry (GC-MS) detection. Histological and ultrastructure observations indicated that 2-MIB caused concentration-dependent inflammatory infiltration and mitochondrial damage in the liver. Transcriptomic analysis revealed lipid metabolism disorders induced by exposure to 2-MIB in grass carp. Additionally, 5 µg L-1 2-MIB affected the neurodevelopment and cardiovascular system of grass carp larvae through extracellular matrix (ECM)-receptor interaction and focal adhesion pathway. Furthermore, several pathways related to the digestive system were significantly enriched, implying that 2-MIB may impact pancreatic secretion function, protein digestion and absorption processes. These findings provide new insights into the potential toxicological mechanisms of 2-MIB.

Cerebral autoregulation: A reliable predictor of prognosis in patients receiving intravenous thrombolysis.

AIMS: To investigate the characteristics of dynamic cerebral autoregulation (dCA) after intravenous thrombolysis (IVT) and assess the relationship between dCA and prognosis. METHODS: Patients with unilateral acute ischemic stroke receiving IVT were prospectively enrolled; those who did not were selected as controls. All patients underwent dCA measurements, by quantifying the phase difference (PD) and gain, at 1-3 and 7-10 days after stroke onset. Simultaneously, two dCA-based nomogram models were established to verify the predictive value of dCA for patients with mild-to-moderate stroke. RESULTS: Finally, 202 patients who received IVT and 238 who did not were included. IVT was positively correlated with higher PD on days 1-3 and 7-10 after stroke onset. PD values in both sides at 1-3 days after stroke onset and in the affected side at 7-10 days after onset were independent predictors of unfavorable outcomes in patients who received IVT. Additionally, in patients with mild-to-moderate stroke who received IVT, the dCA-based nomogram models significantly improved the risk predictive ability for 3-month unfavorable outcomes. CONCLUSION: IVT has a positive effect on dCA in patients with acute stroke; furthermore, dCA may be useful to predict the prognosis of patients with IVT.

Availability of family care resources, bathing assistance and toileting assistance among older adults with functional limitations: an evidence-based study from China.

BACKGROUND: An aging population has contributed to an increasing prevalence of functional limitations among older adults. Family support plays a crucial role in toileting and bathing assistance. Yet, the relationship between availability of family care resources and such actual assistance remains insufficiently explored. Our study aims to describe availability of family care resources and identify the association between availability of family care resources and toileting assistance or bathing assistance. METHODS: This study employed a cross-sectional analysis of data from the 2018 National Survey of the China Health and Retirement Longitudinal Study (CHARLS). The availability of family care resources was assessed using measurements of spouse availability, adult child availability, and living arrangement. Bathing assistance and toileting assistance were measured based on self-reported receipt of such assistance. Descriptive statistics were used to depict the overall and subgroup situation of availability of family care resources. Multivariable logistic models were employed to investigate the relationship between availability of family care resources and the receipt of toileting assistance or bathing assistance. RESULTS: Among the sample of older adults with functional limitations, 69% had a spouse, 63% had at least one adult child, and 80% resided with family members. Among those with bathing disability, 13% reported lacking bathing assistance, and among those with toileting disability, 54% reported lacking toileting assistance. Participants with 1-2 adult children had lower odds of receiving toileting assistance (OR: 0.28, 95% CI: 0.09, 0.91, p= 0.034) compared to those with three or more adult children. Spouse availability and living arrangement did not exhibit statistically significant associations with toileting assistance. Participants without a spouse had lower odds of receiving bathing assistance (OR: 0.27, 95% CI: 0.09-0.78, p= 0.016) in comparison to those with a spouse; however, adult child availability and living arrangement did not display statistically significant associations with bathing assistance. CONCLUSION: The present findings suggest a gap in family commitment when it comes to assisting older adults with functional limitations in bathing/toileting. To address this, policymakers are encouraged to prioritize the implementation of proactive mechanisms for identifying family caregivers, alongside incentives to enhance their engagement in practical caregiving activities. Furthermore, it is crucial to emphasize the prioritization of affordable and easily accessible formal toileting/bathing assistance options for older adults who lack sufficient family care resources.

Csn5 inhibits autophagy by regulating the ubiquitination of Atg6 and Tor to mediate the pathogenicity of Magnaporthe oryzae.

Csn5 is subunit 5 of the COP9 signalosome (CSN), but the mechanism by which it strictly controls the pathogenicity of pathogenic fungi through autophagy remains unclear. Here, we found that Csn5 deficiency attenuated pathogenicity and enhanced autophagy in Magnaporthe oryzae. MoCSN5 knockout led to overubiquitination and overdegradation of MoTor (the core protein of the TORC1 complex [target of rapamycin]) thereby promoted autophagy. In addition, we identified MoCsn5 as a new interactor of MoAtg6. Atg6 was found to be ubiquitinated through linkage with lysine 48 (K48) in cells, which is necessary for infection-associated autophagy in pathogenic fungi. K48-ubiquitination of Atg6 enhanced its degradation and thereby inhibited autophagic activity. Our experimental results indicated that MoCsn5 promoted K48-ubiquitination of MoAtg6, which reduced the MoAtg6 protein content and thus inhibited autophagy. Aberrant ubiquitination and autophagy in ΔMocsn5 led to pleiotropic defects in the growth, development, stress resistance, and pathogenicity of M. oryzae. In summary, our study revealed a novel mechanism by which Csn5 regulates autophagy and pathogenicity in rice blast fungus through ubiquitination.

Electrochemical Synthesis of C(sp3)-Rich Amines by Aminative Carbofunctionalization of Carbonyl Compounds.

Alkylamines form the backbone of countless nitrogen-containing small molecules possessing desirable biological properties. Despite advances in amine synthesis through transition metal catalysis and photoredox chemistry, multicomponent reactions that leverage inexpensive materials to transform abundant chemical feedstocks into three-dimensional α-substituted alkylamines bearing complex substitution patterns remain scarce. Here, we report the design of a catalyst-free electroreductive manifold that merges amines, carbonyl compounds and carbon-based radical acceptors under ambient conditions without rigorous exclusion of air and moisture. Key to this aminative carbofunctionalization process is the chemoselective generation of nucleophilic α-amino radical intermediates that readily couple with electrophilic partners, providing straightforward access to architecturally intricate alkylamines and drug-like scaffolds which are inaccessible by conventional means.

Repeat Surgery after Percutaneous Endoscopic Lumbar Discectomy for Adolescent Lumbar Disc Herniation: A Multicenter Observational Study.

OBJECTIVE: The reported date in the repeat surgical intervention for adolescent lumbar disc herniation (ALDH) after percutaneous endoscopic lumbar discectomy (PELD) was quite scarce. This study aims to introduce cases of repeat surgeries after PELD for ALDH and assess the incidence, chief causes, repeat surgery methods, and surgical outcomes of repeat surgeries after PELD for ALDH. METHODS: A retrospective multicenter observational study was conducted on patients undergoing repeat surgeries after PELD for ALDH at four tertiary referral hospitals from January 2014 through August 2022. The incidence of repeat surgeries, chief causes, strategies for repeat surgeries, and timing of repeat surgeries were recorded and analyzed. The clinical outcomes were evaluated by the Numeric Rating Scales (NRS) scores and the modified MacNab criteria. Statistical analyses were performed with the Wilcoxon signed-rank test. RESULTS: A total of 23 patients who underwent repeat surgeries after PELD for ALDH were included. The chief causes were re-herniation (homo-lateral re-herniation at the same level, new disc herniation of adjacent level). The repeat surgery methods were revision PELD, micro-endoscopic discectomy (MED), open discectomy and instrumented lumbar inter-body fusion. The NRS scores decreased significantly in follow-up evaluations and these scores demonstrated significant improvement at the last follow-up (p < 0.002). For the modified MacNab criteria, at the last follow-up, 18 patients (78.26%) had an excellent outcome, and the overall success rate was 86.95%. CONCLUSION: This study's data suggest that young patients who underwent repeat surgery improved significantly compared to baseline. The chief cause was re-herniation. Revision PELD was the main surgical procedure, which provides satisfactory clinical results in young patients who underwent repeat surgeries.

Influence of adjuvant chemotherapy on survival for patients with completely resected high-risk stage IB NSCLC.

BACKGROUND: The use of adjuvant chemotherapy (ACT) in completely resected stage IB NSCLC is still controversial. This study aims to investigate the efficacy of ACT in pathological stage IB non-small cell lung cancer (NSCLC) with high risk factors. METHODS: Patients with pT2aN0M0 stage IB NSCLC who underwent complete resection from 2013 to 2017 were retrospectively analyzed. Univariate and multivariable logistic regression analysis was used to assess potential independent risk factors associated with poor prognosis. To compare survival between patients who received ACT and those who did not. RESULTS: In univariate and multivariate analyses, adenocarcinomas with predominantly micropapillary (MIP) and solid patterns (SOL), poorly differentiated squamous cell carcinoma (SCC), number of lymph nodes dissected less than 16 and tumor size larger than 36 mm were identified as high-risk factors for recurrence. In patients with high risk factors for recurrence, ACT resulted in significantly longer DFS (HR, 0.4689, 95%CI, 1.193-3.818; p = 0.0108) and OS (HR, 0.4696, 95%CI, 0.6578-6.895; p = 0.2073), although OS failed to reach statistically significance. After propensity score matching (PSM), 67 pairs of patients were 1:1 matched in the two groups and all baseline characteristics were well balanced. The results also demonstrated that ACT was associated with improved DFS (HR, 0.4776, 95%CI, 0.9779-4.484; p = 0.0440) while OS was not significantly different (92.5% vs. 91.0%; HR, 0.6167, 95%CI, 0.1688-2.038; p = 0.7458). In patients with low-risk factors for recurrence, DFS (HR, 0.4831, 95%CI, 0.03025-7.715; p = 0.6068) and OS (HR, 0.969, 95%CI, 0.08364-11.21; p = 0.9794) was not significantly different between those who received ACT and those who did not. CONCLUSION: In patients with completely resected stage IB NSCLC, ACT can improve survival in patients with high risk for recurrence. Further large multicenter studies are needed to confirm these findings.

Clinical impact of sarcopenia for overweight or obese patients with colorectal cancer.

BACKGROUND: Sarcopenia, overweight and obesity are all dynamic changes in body composition, which may have a negative effect on the prognosis for patients with colorectal cancer. The aim of this study was to investigate the predictive role of sarcopenia on overweight or obese patients with colorectal cancer. METHODS: We conducted an observative study on the population of overweight or obese patients with colorectal cancer who underwent curative surgeries in two centers between 2015 and 2021. They were grouped by the presence of sarcopenia. Propensity score match analysis was used to balance the baseline of clinicopathologic characteristics of the two groups. Then, the postoperative outcomes between the two groups were compared. Independent risk factors were evaluated for complications using univariate and multivariate analysis. RESULTS: Of 827 patients enrolled, 126 patients were matched for analysis. Patients with sarcopenia had a higher incidence of total complication and medical complications, a higher rate of laparoscopic surgery performed and higher hospitalization costs. Old age (≥65 years, P = 0.012), ASA grade (III, P = 0.008) and sarcopenia (P = 0.036) were independent risk factors for total complications. ASA grade (III, P = 0.002) and sarcopenia (P = 0.017) were independent risk factors for medical complications. CONCLUSIONS: Sarcopenia was prevalent among overweight or obese patients with colorectal cancer and was associated with negative postoperative outcomes. Early recognition of changes in body composition could help surgeons be well prepared for surgical treatment for overweight or obese patients.

Increased circulating microRNA-21 level as a potential indicator for predicting a higher risk of incident fragility fractures.

CONTEXT: As a common disease in the elderly, osteoporosis clearly increases the risk of fractures, leading to higher mortality, but the current markers to estimate the risk of fractures are limited. MicroRNA-21 (miR-21) may play an important role in osteoporosis, but the link of this biomarker with fractures was undetermined. OBJECTIVES: We aimed to investigate the association between miR-21 levels and the presence of fragility fractures. METHODS: A total of 200 patients were recruited and miR-21 was collected from baseline serum. The correlation between miR-21 and the fracture risk assessment tool (FRAX) score was analyzed. The incidence of fragility fractures was presented by Kaplan-Meier analysis, and Cox regression analysis was utilized to evaluate risk factors. The diagnostic value of miR-21 was conducted by the area under curve (AUC). RESULTS: The FRAX score was significantly associated with miR-21 level (p<0.001). According to the 50th percentile of miR-21 content in the overall distribution, the cumulative incidence of fragility fractures was significantly higher in patients with higher miR-21 levels than those with lower levels (75.4, 95 % CI: 69.0-81.8 vs. 59.2, 95 % CI: 42.1-76.3, p<0.001). The results of the Cox regression analysis showed that the miR-21 level was an independent risk factor linked to the incidence of fracture (p=0.005). The optimal cut-off value of the miR-21 was 6.08, and the AUC for predicting fracture was 0.718 (95 % CI, 0.645-0.790). CONCLUSIONS: This study showed that miR-21 has optimal diagnostic performance in the discrimination of fragility fracture, and the circulating miR-21 level in predicting the risk of fragility fracture may have a certain value.

Establishment and validation of novel nomograms to predict muscle quality in colorectal cancer patients.

OBJECTIVES: The skeletal muscle mass index and skeletal muscle radiodensity have promise as specific diagnostic indicators for muscle quality. However, the difficulties in measuring low skeletal muscle mass index and low skeletal muscle radiodensity limit their use in routine clinical practice, impeding early screening and diagnosis. The objective of this study is to develop a nomogram that incorporates preoperative factors for predicting low skeletal muscle mass index and low skeletal muscle radiodensity. METHODS: A total of 1692 colorectal cancer patients between 2015 and 2021 were included. The patients were randomly divided into a training cohort (n = 1353) and a validation cohort (n = 339). Nomogram models were calibrated using the area under the curve, calibration curves, and the Hosmer-Lemeshow test to assess their predictive ability. Finally, a decision curve was applied to assess the clinical usefulness. RESULTS: In a prediction model for low skeletal muscle mass index, age, body mass index, and grip strength were incorporated as variables. For low skeletal muscle radiodensity, age, sex, body mass index, serum hemoglobin level, and grip strength were included as predictors. In the training cohort, the area under the curve value for low skeletal muscle mass index was 0.750 (95% CI, 0.726-0.773), whereas for low skeletal muscle radiodensity, it was 0.763 (95% CI, 0.739-0.785). The Hosmer-Lemeshow test confirmed that both models fit well in both cohorts. Decision curve analysis was applied to assess the clinical usefulness of the model. CONCLUSIONS: The incorporation of preoperative factors into the nomogram-based prediction model represents a significant advancement in the muscle quality assessment. Its implementation has the potential to early screen patients at risk of low skeletal muscle mass index and low skeletal muscle radiodensity.

Dynamic Cerebral Autoregulation After Carotid Endarterectomy.

OBJECTIVE: Studies have shown that dynamic cerebral autoregulation (dCA) is impaired in patients with severe internal carotid artery (ICA) stenosis and that carotid endarterectomy (CEA) may improve dCA in these patients. However, the time course of dCA changes in patients after CEA remains unclear. Therefore, this study aimed to investigate the effects of CEA on the dCA in patients with carotid artery stenosis at different time points. METHODS: This prospective study enrolled 44 patients (19 symptomatic stenosis patients and 25 asymptomatic stenosis patients) who underwent CEA and 44 age- and sex-matched controls. In the CEA group, the patients underwent dCA measurements at baseline, within 3 days, and 1 month after CEA. Transfer function parameters, phase difference (PD), and gain were used to quantify dCA. Changes in dCA before and after CEA were analyzed in detail. RESULTS: The bilateral PD of the patients before CEA was significantly lower than that of the control group. This damage did not improve within 3 days after surgery. One month after surgery, the PD on the affected side of the patients significantly improved compared with before surgery and reached the level of the control group. The PD of affected side across time points in symptomatic and asymptomatic stenosis patients is consistent with that in all patients. CONCLUSIONS: The dCA level did not improve immediately after CEA but significantly improved 1 month after surgery. This suggests that the occurrence of stroke should be considered in the acute period after CEA surgery, and its preventive effect on stroke may be effective after 1 month. CLINICAL IMPACT: We found the dCA level did not improve immediately after CEA but significantly improved 1 month after surgury. This suggests that the occuttencce of stroke and surgical complications (such as cerebral hyperperfusion syndrome) associated with impaired dCA in the acute phase after CEA surgery should be of particular concern.

CRH neurons in the lateral hypothalamic area regulate feeding behavior of mice.

Food cues serve as pivotal triggers for eliciting physiological responses that subsequently influence food consumption. The magnitude of response induced by these cues stands as a critical determinant in the context of obesity risk. Nonetheless, the underlying neural mechanism that underpins how cues associated with edible food potentiate feeding behaviors remains uncertain. In this study, we revealed that corticotropin-releasing hormone (CRH)-expressing neurons in the lateral hypothalamic area played a crucial role in promoting consummatory behaviors in mice, shedding light on this intricate process. By employing an array of diverse assays, we initially established the activation of these neurons during feeding. Manipulations using optogenetic and chemogenetic assays revealed that their activation amplified appetite and promoted feeding behaviors, whereas inhibition decreased them. Additionally, our investigation identified downstream targets, including the ventral tegmental area, and underscored the pivotal involvement of the CRH neuropeptide itself in orchestrating this regulatory network. This research casts a clarifying light on the neural mechanism underlying the augmentation of appetite and the facilitation of feeding behaviors in response to food cues. VIDEO ABSTRACT.

Core-Shell Reactor Partitioning Enzyme and Prodrug by ZIF-8 for NADPH-Sensitive In Situ Prodrug Activation.

Enzyme-prodrug therapies have shown unique advantages in efficiency, selectivity, and specificity of in vivo prodrug activation. However, precise spatiotemporal control of both the enzyme and its substrate at the target site, preservation of enzyme activity, and in situ substrate depletion due to low prodrug delivery efficiency continue to be great challenges. Here, we propose a novel core-shell reactor partitioning enzyme and prodrug by ZIF-8, which integrates an enzyme with its substrate and increases the drug loading capacity (DLC) using a prodrug as the building ligand to form a Zn-prodrug shell. Cytochrome P450 (CYP450) is immobilized in ZIF-8, and the antitumor drug dacarbazine (DTIC) is coordinated and deposited in its outer layer with a high DLC of 43.6±0.8 %. With this configuration, a much higher prodrug conversion efficiency of CYP450 (36.5±1.5 %) and lower IC50 value (26.3±2.6 µg/mL) are measured for B16-F10 cells with a higher NADPH concentration than those of L02 cells and HUVECs. With the tumor targeting ability of hyaluronic acid, this core-shell enzyme reactor shows a high tumor suppression rate of 96.6±1.9 % and provides a simple and versatile strategy for enabling in vivo biocatalysis to be more efficient, selective, and safer.

The efficacy of three-ball breathing apparatus exercise based on the concept of pulmonary rehabilitation in patients after lung cancer surgery.

BACKGROUND: Postoperative patients with lung cancer mostly experience different degrees of dyspnea and decreased activity tolerance, and these symptoms all significantly affect postoperative quality of life. The concept of pulmonary rehabilitation applicable to patients with chronic respiratory diseases is also applicable to patients with postoperative lung cancer. The current application of postoperative pulmonary rehabilitation for lung cancer is inconsistent, and reliable guidelines are lacking. The purpose of this study was to further verify the efficacy and feasibility of postoperative pulmonary rehabilitation for lung cancer patients, and to find a suitable local pulmonary rehabilitation program for postoperative patients with lung cancer that is clinically promoted in our department through this study. METHODS: We collected the clinical data of patients undergoing video-assisted thoracoscopic surgery (VATS) wedge resection or lobectomy. The patients were divided into rehabilitation group (using three-ball breathing apparatus after discharge) and control group (routine follow-up after discharge) according to whether the patients were trained with three-ball breathing apparatus after operation. The detailed method using three-ball apparatus is as follows. To begin with, patients are required to put themselves in a comfortable position. Then, after the three-ball breathing apparatus put on the same plane of their eyes, patients hold the tube in their mouth closely and control their breath slowly. When patients inhale to their largest extent, the balls will rise up accordingly. Then they exhale. The evaluation results of pulmonary function, activity tolerance, anxiety scores and others were collected. All data was gathered at the First Affiliated Hospital of Soochow University. The effects of pulmonary rehabilitation training on wedge resection and lobectomy were compared. RESULTS: A total of 210 patients were included in this study, including 126 patients with VATS wedge resection and 84 patients with VATS lobectomies. No discrepancy was noticed when FEV1 loss between two groups were compared in the wedge resection patients, and the same results were also shown in patients undergoing lobectomy (12.8% ± 2.0% vs. 12.7% ± 1.9%, P = 0.84, wedge resection; 12.6% ± 2.9% vs. 12.1% ± 1.8%, P = 0.37, lobectomy). The loss of FVC in the control group was greater than that in the rehabilitation group for patients undergoing lobectomy (11.7% ± 5.2%, vs. 17.1% ± 5.6%, P < 0.001, lobectomy). No difference was found in the wedge resection patients between the control and rehabilitation groups (6.6% ± 2.8%, vs. 6.4% ± 3.2%, P = 0.76, lobectomy). Moreover, all patients showed no significant difference in 6MWD regardless of surgical procedure and with or without breathing exercises at T3 (392.6 ± 50.6 m, rehabilitation group vs. 394.0 ± 46.6 m, control group. P = 0.87, wedge resection; 381.3 ± 38.9 m, rehabilitation group vs. 369.1 ± 49.3 m, control group. P = 0.21, lobectomy). CONCLUSIONS: For patients after thoracoscopic pulmonary wedge resection, the use of three-ball apparatus did not significantly improve postoperative pulmonary function and activity tolerance, dyspnea, and anxiety symptoms. In patients after thoracoscopic lobectomy, respiratory trainers were able to improve postoperative lung function but were unable to significantly improve dyspnea and anxiety symptoms. There was a significant benefit for the use of three-ball apparatus in patients after thoracoscopic lobectomy, whereas there was no significant benefit for the use of respiratory trainers after wedge resection. Registry: Medical Ethics Committee of the First Affiliated Hospital of Soochow University. REGISTRATION NUMBER: no. 2022455.

MoCbp7, a Novel Calcineurin B Subunit-Binding Protein, Is Involved in the Calcium Signaling Pathway and Regulates Fungal Development, Virulence, and ER Homeostasis in Magnaporthe oryzae.

Calcineurin, a key regulator of the calcium signaling pathway, is involved in calcium signal transduction and calcium ion homeostasis. Magnaporthe oryzae is a devastating filamentous phytopathogenic fungus in rice, yet little is known about the function of the calcium signaling system. Here, we identified a novel calcineurin regulatory-subunit-binding protein, MoCbp7, which is highly conserved in filamentous fungi and was found to localize in the cytoplasm. Phenotypic analysis of the MoCBP7 gene deletion mutant (ΔMocbp7) showed that MoCbp7 influenced the growth, conidiation, appressorium formation, invasive growth, and virulence of M. oryzae. Some calcium-signaling-related genes, such as YVC1, VCX1, and RCN1, are expressed in a calcineurin/MoCbp7-dependent manner. Furthermore, MoCbp7 synergizes with calcineurin to regulate endoplasmic reticulum homeostasis. Our research indicated that M. oryzae may have evolved a new calcium signaling regulatory network to adapt to its environment compared to the fungal model organism Saccharomyces cerevisiae.

A novel insight into the key gene signature associated with the immune landscape in the progression of sarcopenia.

Sarcopenia is an age-related skeletal muscle disorder that causes falls, disability and death in the elderly, but its exact mechanism remains unknown. In this study, we merged three GEO datasets into the expression profiles of 118 samples and screened 22 differentially expressed genes (DEGs) as candidate genes. Pathway analysis demonstrated that the functional enrichment of DEGs is mainly in the cellular response to insulin stimulus, PPAR signaling pathway and other metabolism-related pathways. Then, we identified six key genes by machine learning, which were confirmed to be closely associated with sarcopenia by bioinformatics analysis. It was experimentally verified that SCD1 exhibits the most substantial alterations in the progression of sarcopenia with disturbed lipid metabolism and myosteatosis. In addition, the immune microenvironment of sarcopenia was found to be affected by these key genes, with Th17 cells down-regulated and NK cells up-regulated. Sarcopenic patients consequently presented a more significant systemic inflammatory state with higher CAR (p = 0.028) and PAR (p = 0.018). For the first time, we identified key genes in sarcopenia with high-throughput data and demonstrated that key genes can regulate the progression of sarcopenia by affecting the immune microenvironment. Among them, SCD1 may influence lipid metabolism and myosteatosis process. Screening of key genes and analyzing of immune microenvironment provide a more accurate target for treating sarcopenia.

Genome Re-Annotation and Transcriptome Analyses of Sanghuangporus sanghuang.

Sanghuangporus sanghuang, the generic type of Sanghuangporus belonging to Hymenochaetaceae, is a precious medicinal wood-inhabiting macrofungus with high commercial potential. To facilitate the medicinal utilization of this fungal resource, transcriptome sequences are newly generated from S. sanghuang strain MS2. In association with the previously generated genome sequences from the same strain by our lab and all available fungal homologous protein sequences in the UniProtKB/Swiss-Prot Protein Sequence Database, a new methodology was employed for genome assembly and annotation. A total of 13,531 protein-coding genes were identified from the new version of the genome of S. sanghuang strain MS2 with a complete BUSCOs of 92.8%, which indicates a remarkable improvement in the accuracy and completeness of the genome assembly. In general, more genes involved in medicinal functions were annotated compared with the original version of the genome annotation, and most of these genes were also found in the transcriptome data of the currently sampled growth period. Given the above, the current genomic and transcriptomic data provides valuable insights into the evolution and metabolites analysis of S. sanghuang.

Plasticity in ventral pallidal cholinergic neuron-derived circuits contributes to comorbid chronic pain-like and depression-like behaviour in male mice.

Nucleus- and cell-specific interrogation of individual basal forebrain (BF) cholinergic circuits is crucial for refining targets to treat comorbid chronic pain-like and depression-like behaviour. As the ventral pallidum (VP) in the BF regulates pain perception and emotions, we aim to address the role of VP-derived cholinergic circuits in hyperalgesia and depression-like behaviour in chronic pain mouse model. In male mice, VP cholinergic neurons innervate local non-cholinergic neurons and modulate downstream basolateral amygdala (BLA) neurons through nicotinic acetylcholine receptors. These cholinergic circuits are mobilized by pain-like stimuli and become hyperactive during persistent pain. Acute stimulation of VP cholinergic neurons and the VP-BLA cholinergic projection reduces pain threshold in naïve mice whereas inhibition of the circuits elevated pain threshold in pain-like states. Multi-day repetitive modulation of the VP-BLA cholinergic pathway regulates depression-like behaviour in persistent pain. Therefore, VP-derived cholinergic circuits are implicated in comorbid hyperalgesia and depression-like behaviour in chronic pain mouse model.