Your preoperative rehabilitation assistant: A study protocol for the impact of a telemedicine-supported preoperative home rehabilitation program on the prognosis of patients undergoing thoracoscopic surgery.

Background: Reduced cardiorespiratory fitness levels are associated with increased short-term complications after surgery, and potentially exert long-lasting effects on the postoperative lives, work and educational pursuits of patients. Currently, research suggests that lifestyle interventions, such as preoperative physical exercise undertaken by patients themselves, may improve patients' cardiopulmonary fitness and reduce post-operative complications. This study aims to investigate the effectiveness and feasibility of a remote medical supervision model for prehabilitation exercise in patients undergoing thoracoscopic lung tumour resection surgery. Methods/Design: All enrolled patients will participate in a 4-week pre-operative exercise intervention to improve their cardiorespiratory fitness. During this period, patients will wear wearable devices and exercise at home based on exercise prescriptions. The exercise prescription comprises aerobic exercise (three times a week or more), muscle strengthening exercise (twice a week or more), and respiratory muscle exercise (once a day). The primary aim is to investigate whether baseline VO2max could be improved following a 4-week preoperative exercise program. Secondary objectives include changes in forced expiratory volume in 1 s and forced vital capacity, degree of acceptance of the technology, quality of life, handgrip strength, postoperative complication rate and length of hospital stay. Discussion: This study aims to evaluate the influence of preoperative prehabilitation exercises in a telemedicine active supervision mode in patients undergoing thoracoscopic lung tumour resection. As such, results of this trial might have some impact on future implementations of group- and home-based prehabilitation exercises in lung cancers. Trial registration: This study was approved by the Medical Ethics Committee of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology (approval number: TJ-IRB20220564) with registration at ClinicalTrials.gov (identifier: NCT05608759).

A wireless, battery-free device for electrical neuromodulation of bladder contractions.

Lower urinary tract dysfunction (LUTD) is a prevalent condition characterized by symptoms such as urinary frequency, urgency, incontinence, and difficulty in urination, which can significantly impair patient's quality of life and lead to severe physiological complications. Despite the availability of diverse treatment options, including pharmaceutical and behavioral therapies, these approaches are not without challenges. The objective of this study was to enhance treatment options for LUTD by developing a wireless, battery-free device for managing bladder contractions. We designed and validated a compact, fully implantable, battery-free pulse generator using the magnetic induction coupling mechanism of wireless power transmission. Weighing less than 0.2 g and with a volume of less than 0.1 cubic centimeters, this device enables precise stimulation of muscles or neurons at voltages ranging from 0 to 10 V. Wireless technology allows real-time adjustment of key stimulation parameters such as voltage, duration, frequency, pulse width, and pulse interval. Our findings demonstrate that the device effectively controlled bladder contractions in mice when used to stimulate the Major Pelvic Ganglion (MPG). Additionally, the device successfully managed micturition in mice with bilateral transection of the pudendal nerve. In conclusion, the development of this innovative wireless pulse generator provides a safer and more cost-effective alternative to conventional battery-powered neurostimulators for bladder control, addressing the limitations of such devices. We anticipate that this novel technology will play a pivotal role in the future of electrical stimulation therapies for voiding dysfunctions.

A rapid and validated GC-MS/MS method for simultaneous quantification of serum Myo- and D-chiro-inositol isomers.

BACKGROUND: Myo-inositol (MI) and D-chiro-inositol (DCI) are two paramount isomers of inositol, both vital in glucose and steroid metabolism. Deficits in MI, DCI or MI/DCI ratio are expressly concerned with several pathological process, whereas MI and DCI lack practical measurement for human specimen. METHODS: To quantify MI and DCI in serum samples simultaneously, a gas chromatography tandem mass spectrometry (GC-MS/MS) method was established. The process flow was optimized in ion source, derivative agent volume and reaction time. The performance characteristics were verified by commercial standards and clinical serums. RESULTS: This method was confirmed to be sensitive (LOD ≤ 30 ng/mL of MI, ≤3 ng/mL of DCI) and reproducible (RSD < 6 % for repeated analyses). Quantitative determinations performed good linearity within the measurement range of 0.500-10.00 and 0.005-0.500 µg/mL for MI and DCI respectively (R2 > 0.999). The recoveries of MI and DCI were 97.11-99.35 % and 107.82-113.09 %, respectively. This method was successfully applied to 114 clinical specimens. No significant matrix effect was observed in serum samples under current conditions.

Stable body sizes in soil nematodes across altitudes: The role of intrageneric variation in community assembly.

Animal body size exhibits rapid responses to environmental variations and displays considerable variability across ecological scales, significantly influencing ecological community assembly. However, our understanding of the extent of body size variation and its responses to environmental differences within soil fauna remains limited, impeding a comprehensive grasp of soil fauna's functional ecology. Here, we aim to investigate the magnitude of intrageneric body size variation and its implications for soil nematode community assembly along an altitudinal gradient. We examined soil nematode body size responses along an altitudinal gradient spanning from 3136 to 4128 m in an alpine mountain region of the eastern Tibetan Plateau. We assessed the contributions of intra- and intergeneric variations in body size, both within and among communities, using individual body size values. The implications of these variations for community assembly processes were determined through phenotypic variance ratios employing permutation tests. Our analyses did not reveal statistically significant correlations between altitude and the community-weighted mean body mass, regardless of considering intrageneric trait variation (IGTV). Approximately 15% of the variation in body size among communities and a substantial 72% of the variation in body size within communities can be attributed to IGTV. Altitude did not significantly affect IGTV within or among communities. Furthermore, our results underscored the dominant role of internal filtering within the community in governing nematode community assembly, with external filtering outside the community playing a limited role within our altitudinal range. Our findings emphasize the dominant role of body size variation within communities rather than among communities, attributable to strong internal filtering processes. These findings advance our understanding of body size variation in soil nematodes across ecological scales and highlight the pivotal role of intrageneric variation in shaping the functional ecology of soil fauna.

Efficacy and safety of mycophenolate mofetil versus cyclophosphamide therapy for Henoch schonlein purpura nephritis in children: A meta-analysis.

OBJECTIVE: The objective of this meta-analysis was to compare the efficacy and safety between glucocorticoids combined with mycophenolate mofetil (MMF) versus glucocorticoids combined with cyclophosphamide (CTX) for henoch schonlein purpura nephritis (HSPN) in children. METHODS: Databases including PubMed, EMbase, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang database were searched from the inception to April 5th, 2024. Eligible studies comparing glucocorticoids combined with MMF versus glucocorticoids combined with CTX for HSPN in children were included. Data were analyzed using Review Manager Version 5.3. RESULTS: Ten studies were included in the meta-analysis. Six randomized controlled trials (RCTs) and 4 non-randomized studies involving 675 patients were identified. Compared with CTX therapeutic schedule, MMF therapeutic schedule had a higher complete remission (CR) within the 6 months (OR 1.61, 95%CI 1.16-2.22, P = .004) and CR within the 12 months (OR 1.73, 95%CI 1.00-2.97, P = .05). However, there was no significant difference between MMF and CTX therapeutic schedule concerning total remission (TR) within the 6 months (OR 1.54, 95%CI 0.82-2.92, P = .18) and TR within the 12 months (OR 2.08, 95%CI 0.86-5.01, P = .10). In addition, incidences of gastrointestinal discomfort (OR 0.33, 95%CI 0.19-0.56, P < .0001), liver function injury (OR 0.28, 95%CI 0.09-0.87, P = .03), myelosuppression (OR 0.15, 95%CI 0.06-0.41, P = .0001), alopecia (OR 0.25, 95%CI 0.07-0.91, P = .03) in MMF therapeutic schedule were all lower than CTX therapeutic schedule. There was no statistically significant difference between the 2 therapeutic schedules concerning infection (OR 0.90, 95%CI 0.50-1.61, P = .72), rash (OR 0.38, 95%CI 0.07-2.04, P = .26). CONCLUSION: Glucocorticoids combined with MMF had a higher CR and lower incidence of adverse effects compared with glucocorticoids combined with CTX in the treatment of HSPN in children.

Non-nitrogen-containing bisphosphonates and nitrogen-containing bisphosphonates for the treatment of atherosclerosis and vascular calcification: A meta-analysis.

BACKGROUND: The role of non-nitrogen-containing bisphosphonates (non-N-BPs) and nitrogen-containing bisphosphonates (N-BPs) in the treatment of atherosclerosis (AS) and vascular calcification (VC) is uncertain. This meta-analysis was conducted to evaluate the efficacy of non-N-BPs and N-BPs in the treatment of AS and VC. METHODS: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases were searched from their inception to July 5th, 2023. Eligible studies comparing bisphosphonates (BPs) versus no BPs in the treatment of AS and VC were included. The data were analyzed using Review Manager Version 5.3. RESULTS: Seventeen studies were included in this meta-analysis. Twelve were randomized control trials (RCTs), and 5 were nonrandomized studies. Overall, 813 patients were included in the BPs group, and 821 patients were included in the no BPs group. Compared with no BP treatment, non-N-BP or N-BP treatment did not affect serum calcium (P > .05), phosphorus (P > .05) or parathyroid hormone (PTH) levels (P > .05). Regarding the effect on serum lipids, non-N-BPs decreased the serum total cholesterol (TC) level (P < .05) and increased the serum triglyceride (TG) level (P < .01) but did not affect the serum low-density lipoprotein cholesterol (LDL-C) level (P > .05). N-BPs did not affect serum TC (P > .05), TG (P > .05) or LDL-C levels (P > .05). Regarding the effect on AS, non-N-BPs did not have a beneficial effect (P > .05). N-BPs had a beneficial effect on AS, including reducing the intima-media thickness (IMT) (P < .05) and plaque area (P < .01). For the effect on VC, non-N-BPs had a beneficial effect (P < .01), but N-BPs did not have a beneficial effect (P > .05). CONCLUSION: Non-N-BPs and N-BPs did not affect serum calcium, phosphorus or PTH levels. Non-N-BPs decreased serum TC levels and increased serum TG levels. N-BPs did not affect serum lipid levels. Non-N-BPs had a beneficial effect on VC, and N-BPs had a beneficial effect on AS.

Effect of folA gene in human breast milk-derived Limosilactobacillus reuteri on its folate biosynthesis.

Introduction: Folate supplementation is crucial for the human body, and the chemically synthesized folic acid might have undesirable side effects. The use of molecular breeding methods to modify the genes related to the biosynthesis of folate by probiotics to increase folate production is currently a focus of research. Methods: In this study, the folate-producing strain of Limosilactobacillus reuteri B1-28 was isolated from human breast milk, and the difference between B1-28 and folA gene deletion strain ΔFolA was investigated by phenotyping, in vitro probiotic evaluation, metabolism and transcriptome analysis. Results: The results showed that the folate producted by the ΔFolA was 2-3 folds that of the B1-28. Scanning electron microscope showed that ΔFolA had rougher surface, and the acid-producing capacity (p = 0.0008) and adhesion properties (p = 0.0096) were significantly enhanced than B1-28. Transcriptomic analysis revealed that differentially expressed genes were mainly involved in three pathways, among which the biosynthesis of ribosome and aminoacyl-tRNA occurred in the key metabolic pathways. Metabolomics analysis showed that folA affected 5 metabolic pathways, involving 89 different metabolites. Discussion: In conclusion, the editing of a key gene of folA in folate biosynthesis pathway provides a feasible pathway to improve folate biosynthesis in breast milk-derived probiotics.

Reliability of Droplet Digital PCR Alone and in Combination with Interleukin-6 and Procalcitonin for Prognosis of Bloodstream Infection.

Purpose: Bloodstream infection(BSI) is linked with high mortality, underscoring the significance of prompt etiological diagnosis for timely and precise treatment. This study aims to investigate the diagnostic value of droplet digital polymerase chain reaction(ddPCR) in combination with conventional inflammatory markers [interleukin-6(IL-6) and procalcitonin(PCT)] concerning disease progression and treatment prognosis in BSI patients. Furthermore, the study aims to explore a more efficient clinical application strategy. Patients and Methods: This prospective case seried study centers on 176 patients suspected of or confirmed with BSI. Blood samples were collected to extract nucleic acids for identifying pathogens (bacteria, fungi, and viruses) and determining copy loads via ddPCR. Results: The sensitivity of ddPCR was markedly higher compared to the culture method (74.71% vs 31.03%). A positive correlation existed between bacterial load and levels of inflammatory markers [IL-6 (P=0.0182), PCT (P=0.0029), and CRP (P=0.0005)]. In suspected BSI cases, the combination of ddPCR and inflammatory markers could predict sepsis risk [ROC: Area under the curve(AUC)=0.6071, P=0.0383]. Within confirmed BSI patients, the ddPCR bacterial load of those with SOFA<7 was lower than that of the SOFA≥7 (P=0.0334). ddPCR (OR: 1.789, P=0.035) monitoring combined with PCT (OR: 1.787, P=0.035) holded predictive value for SOFA progression (AUC=0.7913, P=0.0003). Similarly, BSI survivors displayed a lower burden than non-survivors (P=0.0170). Additionally, ddPCR combinated with IL-6 provided a more accurate and expedited insight into clinical outcomes prediction for BSI confirmed patients (AUC=0.7352, P=0.0030). Serial monitoring of bacterial load by ddPCR effectively mirrored the clinical course of BSI in patients. Notably, patients with positive ddPCR virus infection exhibited significantly reduced lymphocyte counts (P=0.0003). Conclusion: In a clinical context, qualitative ddPCR results and quantitative continuous monitoring can more precisely assess sepsis progression and treatment prognosis in BSI patients. Furthermore, ddPCR results offer quicker and more accurate reference points for clinical antibacterial and antiviral interventions.

Bacterial heat shock protein: A new crosstalk between T lymphocyte and macrophage via JAK2/STAT1 pathway in bloodstream infection.

Bloodstream infection (BSI) refers to the infection of blood by pathogens. Severe immune response to BSI can lead to sepsis, a systemic infection leading to multiple organ dysfunction, coupled with drug resistance, mortality, and limited clinical treatment options. This work aims to further investigate the new interplay between bacterial exocrine regulatory protein and host immune cells in the context of highly drug-resistant malignant BSI. Whether interfering with related regulatory signaling pathways can reverse the inflammatory disorder of immune cells. In-depth analysis of single-cell sequencing results in Septic patients for potential immunodeficiency factors. Analysis of key proteins enriched by host cells and key pathways using proteomics. Cell models and animal models validate the pathological effects of DnaK on T cells, MAITs, macrophages, and osteoclasts. The blood of patients was analyzed for the immunosuppression of T cells and MAITs. We identified that S. maltophilia-DnaK was enriched in immunodeficient T cells. The activation of the JAK2/STAT1 axis initiated the exhaustion of T cells. Septic patients with Gram-negative bacterial infections exhibited deficiencies in MAITs, which correspond to IFN-γ. Cellular and animal experiments confirmed that DnaK could facilitate MAIT depletion and M1 polarization of macrophages. Additionally, Fludarabine mitigated M1 polarization of blood, liver, and spleen in mice. Interestingly, DnaK also repressed osteoclastogenesis of macrophages stimulated by RANKL. S.maltophilia-DnaK prompts the activation of the JAK2/STAT1 axis in T cells and the M1 polarization of macrophages. Targeting the DnaK's crosstalk can be a potentially effective approach for treating the inflammatory disorder in the broad-spectrum drug-resistant BSI.

Deciphering the biotic and abiotic drivers of coalescence asymmetry between soil and manure microbiomes.

Manure application improves soil fertility, yet its implications on the success of invasion of manure-borne microorganisms in the soil are poorly understood. Here, we assessed the importance of abiotic and biotic factors in modulating the extent to which manure-borne fungal and bacterial communities can invade resident soil microbial communities. For this purpose, we applied varying frequencies of two different amounts of manure to nine soils differing in physico-chemical properties, as well as in land-use history, over 180 days and monitored changes in bacterial and fungal communities. Variance partitioning revealed differential contributions of abiotic and biotic factors to invasion success, which together accounted for up to 82 % of the variance explained. We showed that the effects of interactions between biotic and abiotic factors increased with coalescence frequency and manure amount for the bacterial and fungal communities, respectively. Both abiotic and biotic factors were important for modulating coalescence asymmetry for the bacterial community, whereas abiotic factors had a greater effect on the fungal community. These results provide new insights into the drivers of coalescence events between manure and resident soil microbial communities. Moreover, our findings highlight the roles of the mixing ratio and frequency of coalescence events in modulating the survival of manure-borne microorganisms.

Full thermal ablation versus partial thermal ablation for secondary hyperparathyroidism: A meta-analysis.

BACKGROUND: Regarding the thermal ablation treatment of refractory secondary hyperparathyroidism (SHPT), there is no consensus on the ablation range of the hyperplastic parathyroid gland. Therefore, this meta-analysis was conducted to evaluate the efficacy and complications between full and partial thermal ablation in patients with refractory SHPT. METHODS: Databases including PubMed, EMbase, the Cochrane Library, CNKI (China National Knowledge Infrastructure), and Wanfang databases were searched from inception to July 1, 2023. Eligible studies comparing full thermal ablation and partial thermal ablation for SHPT were included. Data were analyzed using Review Manager Version 5.3. RESULTS: Four studies were included in the meta-analysis. Three cohort studies and one randomized controlled trial involving 62 patients in the full thermal ablation group and 63 patients in the partial thermal ablation group were included. The serum parathyroid hormone (PTH), calcium, and phosphorus levels after full ablation were all lower than those after partial ablation (P < .05). There was no significant difference between the partial and full ablation groups concerning the incidence rate of severe hypocalcemia (P = .09). There was no significant difference between the partial and full ablation groups concerning symptom improvement, including bone joint pain, itching, and myasthenia (P < .05). CONCLUSION: Full ablation was superior to partial ablation in terms of reducing PTH, calcium and phosphorus levels. Full ablation might not significantly increase the incidence of severe hypocalcemia. Larger multicentre randomized controlled trials are necessary to confirm the conclusion.

Pulsatillae radix extract alleviates DSS-induced colitis via modulating gut microbiota and inflammatory signaling pathway in mice.

Ethnopharmacological relevance: Ulcerative colitis (UC) is a chronic relapsing intestinal disease with complex pathogenesis. The increasing morbidity and mortality of UC become a global public health threat. Baitouweng decoction (BD), a formulated prescription of Traditional Chinese Medicine, has been applied to cure UC for many centuries. However, the therapeutic efficacy and working mechanisms of this medicine are not well studied. Aim of study: In this study we determined whether Pulsatillae radix, one of four ingredients in BD, had a therapeutic effect on colitis. And explore the underlying mechanism of Pulsatilla chinensis (Bunge) Regel radix in the improvement of DSS-induced colitis in mice model. Methods: The active compounds of Pulsatilla chinensis was identified by UPLC. The composition of the mice's cecum microbiota was determined by 16S rRNA sequencing. And gene expression profile of colon was detected by transcriptome. Results: The results showed that Pulsatillae radix significantly improved the clinical symptom, prevented the shorten of colon length, and decreased the diseased activity index (DAI) in an 3 % DSS-induced ulcerative colitis mouse model. We found that Pulsatillae radix reversed the dysbiosis of gut microbiota as evidenced by increase in the relative abundance of Bacteroidetes, Deferribacteres, and Proteobacteria phyla and decrease in Firmicutes, as well as by decrease in the genera levels of Bacteroides, Parabacteroides, Prevotella, Mucispirillum, Coprococcus, Oscillospira, and Escherichia. The results of transcriptome showed Pulsatillae radix administration led to 128 genes up-regulation, and 122 genes down-regulation, up-regulate NOD-like receptor signaling pathway, down-regulate Cytokine-cytokine receptor interaction, and TNF and IL-17 signaling pathways. Conclusion: in this study, we demonstrate Pulsatillae radix alleviates DSS-induced colitis probably via modulating gut microbiota and inflammatory signaling pathway in DSS-induced colitis mouse model.

An evaluation based on the analytic hierarchy process and GGEbiplot on French fry potato genotypes in Yunnan, China.

A total of 33 potato (Solanum tuberosum L.) cultivars and breeding clones imported from the United States and two local cultivars (Yunshu 401 and Cooperation 88, CK) were planted and evaluated. To determine their suitability for processing into French fries at five locations (e1-e5) in Yunnan Province, China, we developed a comprehensive evaluation system using the analytical hierarchy process (AHP). Eleven evaluation indicators for French fry quality, yield, and agronomic characteristics with a relative importance (weight coefficients) of 0.483, 0.301 and 0.216, respectively, were used to analyze the 35 potato genotypes (designated g1-g35).The genotypes were ranked and the results revealed that (1) on the average, the 33 potato genotypes imported from the United States showed a lower performance compared to the local cultivars. Compared with the CK, they were classified as not vigorous (Mean 5.11 vs CK 7.75), matured earlier (Mean 5.79 vs CK 1.70), and had a low resistance to late blight (Mean 3735.59 vs CK 1418.55), requiring the use of fungicides to control the disease at the five trial locations. (2) The US cultivar 'Defender' (g3) ranked in the top six at all five test locations because it had higher yield (29.56 t h m-2), better fry quality (4.64), higher dry matter content (20.41%), better tuber length/width ratio (1.99), longer tubers (13.57cm), stronger plant vigor (7.17) and higher resistance to late blight (AUDPC: 3134.2). (3) By using GGEbiplot analysis, superior genotypes with high and stable yields were g3 and 'Echo Russet' (g33). 'Yunshu 401' (g34) and 'Yukon Gem' (g4) had high but not stable yields. The ideal test environments and hence experimental locations were Luquan (LQ, e2) and Lijiang (LJ, e4) which resulted in the best discrimination between genotypes among the five experimental locations in Yunnan. Overall, the developed evaluation system based on AHP and GGEbiplot analysis including 11 evaluation indicators for French fry quality, yield and agricultural traits can be a model for evaluation and promotion of new French fry cultivars, and evaluating and selecting the test location.

In vitro Activity of Cefepime/Avibactam Against Carbapenem Resistant Klebsiella pneumoniae and Integrative Metabolomics-Proteomics Approach for Resistance Mechanism: A Single-Center Study.

Purpose: We aimed to evaluate the in vitro antibacterial effects of combination of cefepime/avibactam against carbapenem-resistant Klebsiella pneumonia (CRKP) and explore the resistance mechanism of FEP/AVI. Patients and Methods: This study explored the in vitro antibacterial activities of ceftazidime/avibactam (CAZ/AVI) and cefepime/avibactam (FEP/AVI) against 40 and 76 CRKP clinical isolates. Proteomics and metabolomics were employed to investigate the resistance mechanisms of CRKP to FEP/AVI. Results: FEP/AVI (MIC50/MIC90 0.5/4-64/4 µg/mL, resistance rate 17.1%) showed better antibacterial activity against CRKP than CAZ/AVI (MIC50/MIC90 4/4-128/4 µg/mL, resistance rate 20%) in vitro. Bioinformatics analysis showed that the differentially expressed proteins (DEPs) were enriched in alanine, aspartate and glutamate metabolism, and ribosome. Remarkably, transcriptional and translational activity-related pathways were inhibited in FEP/AVI resistant CRKP. Overlap analysis suggested that H-NS might play an important role in resistance to FEP/AVI in CRKP. The mRNA levels of DEPs-related genes (adhE, gltB, purA, ftsI and hns) showed the same trends as DEPs in FEP/AVI susceptible and resistant strains. FEP/AVI resistant isolates demonstrated stronger biofilm formation capacity than susceptible isolates. Metabolomics results showed that disturbed metabolites were mainly lipids, and adenine was decreased in FEP/AVI resistant CRKP. Conclusion: These results indicated that H-NS, GltB and SpoT may directly or indirectly promote biofilm formation of CRKP and led to FEP/AVI resistance, but inhibited ribosomal function. Our study provides a mechanistic insight into the acquisition of resistance to FEP/AVI in Klebsiella pneumoniae.

Effects of Lactiplantibacillus plantarum GUANKE on Diphenoxylate-Induced Slow Transit Constipation and Gut Microbiota in Mice.

Slow transit constipation (STC) is a prevalent gastrointestinal condition with slow transit, and some probiotics can effectively relieve constipation, but the exact mechanisms have not been fully understood. In this study, we evaluate the impact of Lactiplantibacillus plantarum GUANKE (GUANKE) on diphenoxylate-induced slow transit constipation and speculate on the underlying mechanisms in a mouse model. Administration of L. plantarum GUANKE alleviated constipation indexes, including defecation time, fecal output and water content, and gastrointestinal transit ratio. In addition, GUANKE restored the protein expression of constipation-related intestinal factors (aquaporins (AQPs) and interstitial Cajal cells (ICCs)) in colon tissues measured using immunofluorescence staining; regulated the neurotransmitters and hormones, such as increased levels of 5-hydroxytryptamine, substance P, and motilin; and decreased levels of vasoactive intestinal peptide and nitric oxide in serum, as measured by an ELISA. 16S rRNA and correlation analysis of feces indicated that GUANKE administration effectively reduced constipation-induced Prevotella enrichment and suggested a potential contribution of Prevotella to diphenoxylate-induced STC in mice. GUANKE had no effect on short-chain fatty acids (SCFAs) in cecum content. This study revealed that GUANKE may alleviate constipation in mice through regulating intestinal neurotransmitter and hormone release and altering specific bacterial taxa, rather than by affecting SCFAs and the diversity of microbiota in the gut. Further research is needed to confirm if the findings observed in this study will be consistent in other animal studies or clinical trials.

Mitochondrial mass of circulating NK cells as a novel biomarker in severe SARS-CoV-2 infection.

BACKGROUND: Severe SARS-CoV-2 infection results in lymphopenia and impaired function of T, B, and NK (TBNK-dominant) lymphocytes. Mitochondria are essential targets of SARS-CoV-2 and the efficacy of lymphocyte mitochondrial function for immunosurveillance in COVID-19 patients has not been evaluated. METHODS: Multi-parametric flow cytometry was used to characterize mitochondrial function, including mitochondrial mass (MM) and low mitochondrial membrane potential (MMPlow), in TBNK-dominant lymphocytes from severe (n = 93) and moderate (n = 77) hospitalized COVID-19 patients. We compared the role of novel lymphocyte mitochondrial indicators and routine infection biomarkers as early predictors of severity and death in COVID-19 patients. We then developed a mortality decision tree prediction model based on immunosurveillance indicators through machine learning. RESULTS: At admission, the MM of circulating NK cells (NK-MM) was the best discriminator of severe/moderate disease (AUC = 0.8067) compared with the routine infection biomarkers. The NK cell count and NK-MM displayed superior diagnostic effects to distinguish patients with non-fatal or fatal outcomes. Interestingly, NK-MM was significantly polarized in non-survivors, with some patients showing a decrease and others showing an abnormal increase. Kaplan-Meier analysis showed that NK-MM had the optimal predictive efficacy (hazard ratio = 11.66). The decision tree model has the highest proportion of importance for NK-MM, which is superior to the single diagnostic effect of the above indicators (AUC = 0.8900). CONCLUSION: NK-MM was not only associated with disease severity, its abnormal increases or decreases also predicted mortality risk. The resulting decision tree prediction model is the first to focus on immune monitoring indicators to provide decision-making clues for COVID-19 clinical management.

IMPA2 blocks cervical cancer cell apoptosis and induces paclitaxel resistance through p53-mediated AIFM2 regulation.

Cervical cancer continues to be a concern, and the prognosis of locally advanced cervical cancer remains poor. IMPA2 was previously identified as a potential oncogene and regulator of tumor apoptosis. In this study, we aim to further elucidate the underlying mechanisms of IMPA2 gene in the regulation of cervical cancer apoptosis. First, we identify AIFM2 as an upregulated gene in IMPA2-silenced cervical cancer cells, and inhibition of AIFM2 reverses IMPA2 knockdown-induced apoptosis. Further study reveals that AIFM2 regulates cell apoptosis in a mitochondrial-dependent manner with a redistribution of mitochondrial membrane potential and intracellular Ca 2+ levels. However, the analysis of the STRING database and our experimental results show that AIFM2 has little effect on cervical cancer progression and survival. Further mechanistic study demonstrates that IMPA2 and AIFM2 silencing inhibits apoptosis by activating p53. Meanwhile, the knockdown of IMPA2 enhances the chemosensitivity of cervical cancer cells by strengthening paclitaxel-induced apoptosis. Based on the above results, the IMPA2/AIFM2/p53 pathway may be a new molecular mechanism for paclitaxel treatment of cervical cancer and an effective strategy to enhance the sensitivity of cervical cancer cells to paclitaxel. Our findings display a novel function of IMPA2 in regulating cell apoptosis and paclitaxel resistance mediated by a disturbance of AIFM2 and p53 expression, potentially making it a novel therapeutic target for cervical cancer treatment.

Novel tumor therapy strategies targeting endoplasmic reticulum-mitochondria signal pathways.

Organelles form tight connections through membrane contact sites, thereby cooperating to regulate homeostasis and cell function. Among them, the contact between endoplasmic reticulum (ER), the main intracellular calcium storage organelles, and mitochondria has been recognized for decades, and its main roles in the ion and lipid transport, ROS signaling, membrane dynamic changes and cellular metabolism are basically determined. At present, many tumor chemotherapeutic drugs rely on ER-mitochondrial calcium signal to function, but the mechanism of targeting resident molecules at the mitochondria-associated endoplasmic reticulum membranes (MAM) to sensitize traditional chemotherapy and the new tumor therapeutic targets identified based on the signal pathways on the MAM have not been thoroughly discussed. In this review, we highlight the key roles of various signaling pathways at the ER-mitochondria contact site in tumorigenesis and focus on novel anticancer therapy strategies targeting potential targets at this contact site.

Lactiplantibacillus pentosus P2020 protects the hyperuricemia and renal inflammation in mice.

Introduction: Hyperuricemia (HUA) is a common metabolic disease, and its prevalence has been increasing worldwide. Pharmaceutical drugs have been used for controlling HUA but they all have certain side effects, which thus calls for discovering alternative options including using treatment of probiotics to prevent the development of HUA. Methods: We established HUA mice model induced by potassium oxonate and adenine and performed in vivo experiments to verify the ability to lower serum uric acid of Lactiplantibacillus pentosus P2020 (LPP), a probiotics stain extracted from Chinese pickle. We also tried to discussed the underlying mechanisms. Results: Oral administration with LPP significantly decreased serum uric acid and reduced renal inflammatory response by downregulating multiple inflammation pathways including NK-kB, MAPK, and TNFα. We also found that LPP administration significantly promoted uric acid excretion by regulating expression of transporters in the kidney and ileum. In addition, LPP intake improved intestinal barrier function and modulated the composition of gut microbiota. Discussion: These results suggest that probiotics LPP may have a promising potential to protect against development of HUA and HUA-related renal damage, and its working mechanisms involve regulation of inflammation pathways and expression of transporters in the kidney and ileum.