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1.
Carbohydr Polym ; 339: 122255, 2024 Sep 01.
Article En | MEDLINE | ID: mdl-38823921

Mixed infectious vaginitis poses a serious threat to female reproductive health due to complex pathogenic factors, a long course and easy recurrence. Currently, antibiotic-based treatment methods are facing a crisis of drug resistance and secondary dysbiosis. Exploring effective drugs for the treatment of mixed vaginitis from Paeonia suffruticosa Andr., a natural traditional Chinese medicine with a long history of medicinal use, is a feasible treatment strategy. P. suffruticosa Andr. leaf extract (PLE) has significant anti-bacterial effects due to its rich content of polyphenols and flavonoids. The polyphenols in peony leaves have the potential to make carboxymethyl chitosan form in situ gel. In the current study, PLE and carboxymethyl chitosan were combined to develop another type of natural anti-bacterial anti-oxidant hydrogel for the treatment of mixed infectious vaginitis. Through a series of characterisations, CP had a three-dimensional network porous structure with good mechanical properties, high water absorption, long retention and a slow-release drug effect. The mixed infectious vaginitis mouse model induced by a mixture of pathogenic bacteria was used to investigate the therapeutic effects of CP in vivo. The appearance of the vagina, H&E colouring of the tissue and inflammatory factors (TNF-α, IL-6) confirm the good anti-vaginal effect of CP. Therefore, CP was expected to become an ideal effective strategy to improve mixed infection vaginitis due to its excellent hydrogel performance and remarkable ability to regulate flora.


Anti-Bacterial Agents , Chitosan , Hydrogels , Paeonia , Plant Extracts , Plant Leaves , Chitosan/chemistry , Chitosan/pharmacology , Chitosan/analogs & derivatives , Female , Animals , Hydrogels/chemistry , Hydrogels/pharmacology , Plant Leaves/chemistry , Mice , Plant Extracts/chemistry , Plant Extracts/pharmacology , Paeonia/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/therapeutic use , Vaginosis, Bacterial/drug therapy , Vaginosis, Bacterial/microbiology , Antioxidants/pharmacology , Antioxidants/chemistry
2.
Stem Cell Res Ther ; 15(1): 158, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38824568

BACKGROUND: Nerve guide conduits are a promising strategy for reconstructing peripheral nerve defects. Improving the survival rate of seed cells in nerve conduits is still a challenge and microcarriers are an excellent three-dimensional (3D) culture scaffold. Here, we investigate the effect of the 3D culture of microcarriers on the biological characteristics of adipose mesenchymal stem cells (ADSCs) and to evaluate the efficacy of chitosan nerve conduits filled with microcarriers loaded with ADSCs in repairing nerve defects. METHODS: In vitro, we prepared porous chitosan microspheres by a modified emulsion cross-linking method for loading ADSCs and evaluated the growth status and function of ADSCs. In vivo, ADSCs-loaded microcarriers were injected into chitosan nerve conduits to repair a 12 mm sciatic nerve defect in rats. RESULTS: Compared to the conventional two-dimensional (2D) culture, the prepared microcarriers were more conducive to the proliferation, migration, and secretion of trophic factors of ADSCs. In addition, gait analysis, neuro-electrophysiology, and histological evaluation of nerves and muscles showed that the ADSC microcarrier-loaded nerve conduits were more effective in improving nerve regeneration. CONCLUSIONS: The ADSCs-loaded chitosan porous microcarrier prepared in this study has a high cell engraftment rate and good potential for peripheral nerve repair.


Adipose Tissue , Chitosan , Mesenchymal Stem Cells , Microspheres , Nerve Regeneration , Rats, Sprague-Dawley , Chitosan/chemistry , Nerve Regeneration/physiology , Animals , Rats , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Adipose Tissue/cytology , Sciatic Nerve/physiology , Porosity , Tissue Scaffolds/chemistry , Male , Mesenchymal Stem Cell Transplantation/methods , Cell Proliferation , Cells, Cultured
3.
Cancer Med ; 13(11): e7326, 2024 Jun.
Article En | MEDLINE | ID: mdl-38826114

BACKGROUND: Optimal adjuvant chemotherapy after laparoscopic surgery in gastric cancer (GC) patients is still undefined. We aimed to evaluate the efficacy of S-1 plus oxaliplatin (SOX) and capecitabine plus oxaliplatin (CAPOX) in patients with GC after laparoscopic gastrectomy. METHODS: A non-inferiority randomized controlled clinical trial was performed in China. Patients with advanced GC who underwent laparoscopic D2 gastrectomy were randomly assigned to receive SOX and CAPOX regimens. RESULTS: In total, 191 patients were screened between May 2018 and June 2019, and 140 (73.3%) were included in the modified intent-to-treat analysis (mITT), of whom 69 and 71 were assigned to the SOX and CAPOX groups, respectively. The SOX group had similar 3-year overall survival (OS) and disease-free survival to the CAPOX group. Subgroup analysis revealed significantly better OS in the SOX group for male patients ([HR] = 0.395; 95% [CI], 0.153-1.019; p = 0.045), age >60 (HR = 0.219; 95% [CI], 0.064-0.753; p = 0.016), tumors in the gastric antrum (HR = 0.273; 95% [CI], 0.076-0.981; p = 0.047), and moderately differentiated tumors (HR = 0.338; 95% [CI], 0.110-1.041; p = 0.041). There were no significant differences observed in terms of adverse events and recurrence patterns between the two groups. CONCLUSION: Adjuvant SOX was non-inferior to CAPOX treatments for patients with GC who underwent curative laparoscopic D2 gastrectomy. For male patients, aged >60 years, tumors in the gastric antrum, and moderately differentiated tumors, adjuvant SOX may achieve an improvement compared with CAPOX.


Antineoplastic Combined Chemotherapy Protocols , Capecitabine , Drug Combinations , Gastrectomy , Laparoscopy , Oxaliplatin , Oxonic Acid , Stomach Neoplasms , Tegafur , Humans , Stomach Neoplasms/surgery , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Stomach Neoplasms/mortality , Male , Gastrectomy/methods , Female , Middle Aged , Laparoscopy/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Oxaliplatin/therapeutic use , Oxaliplatin/administration & dosage , Tegafur/therapeutic use , Tegafur/administration & dosage , Oxonic Acid/therapeutic use , Oxonic Acid/administration & dosage , Chemotherapy, Adjuvant/methods , Capecitabine/administration & dosage , Capecitabine/therapeutic use , Aged , Adult
4.
Article En | MEDLINE | ID: mdl-38778369

BACKGROUND: Metabolic syndrome (MetS), a condition that includes several risk factors specific for cardiovascular disease, is commonly detected among patients with schizophrenia (SCZ). This study elucidated the factors contributing to the development and severity of MetS in first-treatment drug-naïve (FTDN) patients with SCZ. METHODS: The study enrolled 668 individuals with FTDN SCZ, aged 18-49 years, who had no exposure to antipsychotic medications and been hospitalized between February 2017 and June 2022 at the largest psychiatric specialty institution in central China. Patient sociodemographic and general clinical data were collected, and their psychopathology scores and illness severity were assessed using the Positive and Negative Symptom Scale (PANSS) and Clinical Global Impression Scale-Severity of Illness (CGI-SI), respectively. MetS score was calculated to determine the disease severity. RESULTS: The prevalence of MetS among this study population was 10.93%. Binary logistic regression analysis revealed onset age, female sex, total cholesterol, and red blood and white blood cell counts as risk factors for MetS, and deemed free tetraiodothyronine (FT4) and CGI-SI score as protective factors. Multiple linear regression analysis result confirmed older SCZ onset age as a risk factor for elevated MetS score. CONCLUSION: This study determined the prevalence of MetS in patients with FTDN SCZ and revealed the factors that influence the occurrence and severity of the disease. These findings will allow development of specific prevention and treatment strategies in clinical practice.

5.
Front Pediatr ; 12: 1362076, 2024.
Article En | MEDLINE | ID: mdl-38783917

Background: A potential association between the onset of diabetes and normal birth weight (NBW) has been discovered. Diverse conclusions and study methodologies exist regarding the connection between low birth weight (LBW) and impaired glucose tolerance in children, underscoring the need for further robust research. Our institution is embarking on this study to thoroughly examine the association between LBW and impaired glucose tolerance in children. Methods: We conducted searches on Cochrane Library, ScienceDirect, EMBASE, PubMed, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature data (CBM) online database, VIP full-text Database, and Wanfang Database to identify correlation analyses or case-control studies investigating the relationship between LBW and abnormal glucose tolerance in children. The search spanned from January 2010 to September 2023. The quality of observational studies was evaluated using the Newcastle-Ottawa Scale (NOS) tool. Data synthesis was performed using the statistical software RevMan 5.3 for meta-analysis. Results: Based on the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines, we finally included 10 clinical control studies consisting of a total of 2971 cases. There wasn't considerably change in blood sugar levels among LBW, NBW and high birth weight (HBW) infants (P > 0.05). There was no significant difference in insulin levels between LBW infants and NBW infants (P > 0.05). The HOMA-IR of LBW infants was considerably higher than that of NBW infants (P < 0.05). The risk of abnormal glucose tolerance in LBW infants was 0.42 times higher than that in NBW and HBW infants [Fisher's Z = 0.42, 95% CI = (0.09, 0.75), P = 0.01]. Conclusion: LBW is associated with an increased risk of abnormal glucose tolerance, as indicated by elevated HOMA-IR level in LBW infants compared to NBW and HBW pediatric population. Further research is needed to confirm and expand upon these findings to better understand the complex relationship between LBW and impaired glucose tolerance in children.

6.
Heliyon ; 10(10): e30568, 2024 May 30.
Article En | MEDLINE | ID: mdl-38784556

Autophagy during myocardial ischemia/reperfusion (MI/R) exacerbates cardiomyocyte injury. Melatonin (Mel) alleviates myocardial damage by regulating mitochondrial function and mitophagy, but the role of mitophagy in melatonin-induced cardioprotection remains unclear. This study aimed to explore the roles of sirtuin3 (SIRT3) and retinoid-related orphan nuclear receptor-α (RORα) in mitophagy during simulated ischemia reperfusion (SIR) in H9c2 cells. Our data showed that mitophagy was excessively activated after SIR injury, which was consistent with reduced cell survival, enhanced oxidative responses and mitochondrial dysfunction in H9c2 myocytes. Melatonin greatly enhanced cell viability, reduced oxidative stress and improved mitochondrial function. The effects of melatonin protection were involved in excessive mitophagy inhibition, as demonstrated by the reduced levels of mitophagy-linked proteins, including Parkin, Beclin1, NIX and BNIP3, and the LC3 II/LC3 I ratio and elevations in p62. Additionally, the decreases in SIRT3 and RORα in H9c2 myocytes after SIR were reversed by melatonin, and the above effects of melatonin were eliminated by small interfering RNA (siRNA)-mediated knockdown of SIRT3 and RORα. In brief, SIRT3 and RORα are two prospective targets in the cardioprotection of melatonin against mitophagy during SIR in H9c2 myocytes.

7.
Spectrochim Acta A Mol Biomol Spectrosc ; 318: 124499, 2024 May 22.
Article En | MEDLINE | ID: mdl-38788505

As a new type of persistent pollutant, microplastics pose a serious threat to the earth's ecological environment and human health. Efficient and reliable microplastic detection technology is of great significance in the management of microplastic pollution. Aiming at the problems of low signal-to-noise ratio (SNR), narrow spectral range and low spectral resolution in traditional microplastic detection technology, a splicing grating spatial heterodyne Raman spectroscopy (SG-SHRS) is proposed in this paper. The splicing grating is composed of four sub-gratings with groove densities of 320, 298, 276 and 254 gr / mm, respectively. Each sub-grating has an independent sub-filter to improve the SNR of the system. The system is simulated, built and calibrated. The actual resolution of the SG-SHRS system is 0.7 cm-1, and the spectral detection range of a single sub-grating is 2947.2 cm-1. Four kinds of microplastics, polyamide (PA), polystyrene (PS), polycarbonate (PC), and polyphenylene sulfide (PPS), were detected by the SG-SHRS system. The complete Raman spectral information of microplastics was obtained, and the peak assignment of Raman characteristic peaks of the four kinds of microplastics was analyzed. By comparing the test results with a commercial dispersion spectrometer, it has been proven that the SG-SHRS system has the advantages of high spectral resolution, wide spectral range, and high SNR, and has good application prospects in the field of microplastic detection.

9.
Water Res ; 257: 121699, 2024 Jun 15.
Article En | MEDLINE | ID: mdl-38713937

The effective activation of natural chalcopyrite (CuFeS2) on peracetic acid (PAA) to remove organic micropollutants was studied under visible light irradiation. Results showed than an effective sulfamethoxazole (SMX) degradation (95.0 %) was achieved under visible light irradiation for 30 min at pH 7.0. Quenching experiments, electron spin resonance analysis, and LC/MS spectrum demonstrated that HO• and CH3C(O)OO• were the main reactive species for SMX degradation, accounting for 43.3 % and 56.7 % of the contributions, respectively. Combined with X-ray photoelectron spectroscopy analysis, the photoelectrons generated on CuFeS2 activated by visible light enhanced the Fe3+/Fe2+ and Cu2+/Cu+ cycles on the surface, thereby activating PAA to generate HO•/CH3C(O)OO•. The removal rate of SMX decreased with the increase in wavelengths, due to the formation of low energy photons at longer wavelengths. Besides, the optimal pH for degradation of SMX by CuFeS2/PAA/Vis-LED process was neutral, which was attributed to the increasing easily activated anionic form of PAA during the increase in pH and the depletion of Fe species at alkaline conditions. Cl-, HCO3-, and HA slightly inhibited SMX degradation because of reactive species being quenched and/or shielding effect. Furthermore, the degradation efficiency of different pollutants by CuFeS2/PAA/Vis-LED was also measured, and the removal efficiency was different owing to the selectivity of CH3C(O)OO•. Finally, the process exhibited good applicability in real waters. Overall, this study provides new insight into visible light-catalyzed activation of PAA and suggests on further exploration of the intrinsic activation mechanism of PAA.


Copper , Peracetic Acid , Water Pollutants, Chemical , Water Pollutants, Chemical/chemistry , Copper/chemistry , Peracetic Acid/chemistry , Light , Hydrogen-Ion Concentration , Sulfamethoxazole/chemistry
10.
Cogn Neurodyn ; 18(2): 673-684, 2024 Apr.
Article En | MEDLINE | ID: mdl-38699608

One-layer membrane separates the gradient field in and out of the cell, while some two-layer membranes filled with excitable media/material are important to regulate the energy flow when ions are propagated and diffused. The intracellular and extracellular media can be effectively separated by the membrane. It is important to clarify and describe the biophysical function and then the capacitive property can be reproduced in equivalent neural circuit. Here, we suggest the cell membrane has certain thickness and becomes flexible under external stimuli, therefore, it is considered as a kind of nonlinear media. To mimic the physical property of the two-layer cell membrane, a nonlinear resistor is used to connect two linear circuits, which is used to describe the electrical characteristic of two sides of the cell membrane, respectively. The combination of two linear circuits via a nonlinear resistor can describe the energy characteristic and firing mode in the flexible membrane of biophysical neurons. Circuit equations are defined and converted into equivalent nonlinear oscillator like a neuron. The voltage difference for the two capacitors can be consistent with the membrane potential for the neuron. The Hamilton energy function for this neuron can be mapped from the field energy in the electronic components, and it is also derived by using Helmholtz's theorem. The neuron can show similar spiking and bursting firing patterns, and uncertain diversity in membrane potentials is effective to support continuous firing patterns and mode transition under external stimulus. Furthermore, noisy disturbance is applied to induce coherence resonance. The results indicate that the lower coefficient variability and higher average energy level supports periodic firing in the neuron under coherence resonance. Therefore, this neuron model with nonlinear membranes (or two-layer form) is more suitable for identifying the biophysical property of biological neuron.

11.
Chemistry ; : e202400223, 2024 May 10.
Article En | MEDLINE | ID: mdl-38728573

We proposed a new strategy for CO2 hydrogenation to prepare light olefins by introducing Zn into GaZrOx to construct ZnGaZrOx ternary oxides, which was combined with SAPO-34 to prepare a high-performance ZnGaZrOx/SAPO-34 tandem catalyst for CO2 hydrogenation to light olefins. By optimizing the Zn doping content, the ratio and mode of the two-phase composite, and the process conditions, the 3.5%ZnGaZrOx/SAPO-34 tandem catalyst showed excellent catalytic performance and good high-temperature inhibition of the reverse water-gas shift (RWGS) reaction. The catalyst achieved 26.6% CO2 conversion, 82.1% C2=-C4= selectivity and 11.8% light olefins yield. The ZnGaZrOx formed by introducing an appropriate amount of Zn into GaZrOx significantly enhanced the spillover H2 effect and also induced the generation of abundant oxygen vacancies to effectively promote the activation of CO2. Importantly, the RWGS reaction was also significantly suppressed at high temperatures, with the CO selectivity being only 46.1% at 390°C.

12.
Chin Med J (Engl) ; 2024 May 09.
Article En | MEDLINE | ID: mdl-38725376

BACKGROUND: The urban-rural disparities in overweight and obesity among children and adolescents are narrowing, and there is a need for long-term and updated data to explain this inequality, understand the underlying mechanisms, and identify priority groups for interventions. METHODS: We analyzed data from seven rounds of the Chinese National Survey on Students Constitution and Health (CNSSCH) conducted from 1985 to 2019, focusing on school-age children and adolescents aged 7-18 years. Joinpoint regression was used to identify inflection points (indicating a change in the trend) in the prevalence of overweight and obesity during the study period, stratified by urban/rural areas and sex. Annual percent change (APC), average annual percent change (AAPC), and 95% confidence interval (CI) were used to describe changes in the prevalence of overweight and obesity. Polynomial regression models were used to predict the prevalence of overweight and obesity among children and adolescents in 2025 and 2030, considering urban/rural areas, sex, and age groups. RESULTS: The prevalence of overweight and obesity in urban boys and girls showed an inflection point of 2000, with AAPC values of 10.09% (95% CI: 7.33-12.92%, t = 7.414, P <0.001) and 8.67% (95% CI: 6.10-11.30%, t = 6.809, P <0.001), respectively. The APC for urban boys decreased from 18.31% (95% CI: 4.72-33.67%, t = 5.926, P = 0.027) to 4.01% (95% CI: 1.33-6.75%, t = 6.486, P = 0.023), while the APC for urban girls decreased from 13.88% (95% CI: 1.82-27.38%, t = 4.994, P = 0.038) to 4.72% (95% CI: 1.43-8.12%, t = 6.215, P = 0.025). However, no inflection points were observed in the best-fit models for rural boys and girls during the period 1985-2019. The prevalence of overweight and obesity for both urban and rural boys is expected to converge at 35.76% by approximately 2027. A similar pattern is observed for urban and rural girls, with a prevalence of overweight and obesity reaching 20.86% in 2025. CONCLUSIONS: The prevalence of overweight and obesity among Chinese children and adolescents has been steadily increasing from 1985 to 2019. A complete reversal in urban-rural prevalence is expected by 2027, with a higher prevalence of overweight and obesity in rural areas. Urgent action is needed to address health inequities and increase investments, particularly policies targeting rural children and adolescents.

13.
Microbiol Spectr ; : e0039024, 2024 May 10.
Article En | MEDLINE | ID: mdl-38727239

Alternaria alternata is a ubiquitous soil-borne fungus capable of causing diseases in a variety of plants and occasionally in humans. While populations of A. alternata from infected plants have received significant attention, relatively little is known about its soil populations, including its population genetic structure and antifungal susceptibilities. In addition, over the last two decades, greenhouses have become increasingly important for food and ornamental plant production throughout the world, but how greenhouses might impact microbial pathogens such as A. alternata populations remains largely unknown. Different from open crop fields, greenhouses are often more intensively cultivated, with each greenhouse being a relatively small and isolated space where temperature and humidity are higher than surrounding environments. Previous studies have shown that greenhouse populations of two common molds, Aspergillus fumigatus and A. alternata, within a small community in southwestern China were variably differentiated. However, the relative contribution of physical separation among local greenhouses to the large-scale population structure remains unknown. Here, we isolated strains of A. alternata from seven greenhouses in Shijiazhuang, northeast China. Their genetic diversity and triazole susceptibilities were analyzed and compared with each other and with 242 isolates from nine greenhouses in Kunming, southwest China. Results showed that the isolation of greenhouses located <1 km from each other locally contributed similarly to the overall genetic variation as that between the two distant geographic regions. In addition, our results indicate that greenhouses could be significant sources of triazole resistance, with greenhouses often differing in their frequencies of resistant strains to different triazoles. IMPORTANCE: Greenhouses have become increasingly important for food production and food security. However, our understanding of how greenhouses may contribute to genetic variations in soil microbial populations is very limited. In this study, we obtained and analyzed soil populations of the cosmopolitan fungal pathogen Alternaria alternata in seven greenhouses in Shijiazhuang, northeast China. Our analyses revealed high proportions of isolates being resistant to agricultural triazole fungicides and medical triazole drugs, including cross-resistance to both groups of triazoles. In addition, we found that greenhouse populations of A. alternata located within a few kilometers showed similar levels of genetic differentiation as those separated by over 2,000 km between northeast and southwest China. Our study suggests that greenhouse populations of this and potentially other fungal pathogens represent an important ecological niche and an emerging threat to food security and human health.

14.
BMC Psychiatry ; 24(1): 396, 2024 May 27.
Article En | MEDLINE | ID: mdl-38802840

BACKGROUND: Major depressive disorder (MDD) is a severe mental illness with high relapse rates and high mortality. Depression not only severely limits psychosocial functioning but also reduces quality of life. It can also negatively affect patients' clinical parameters, including lipid metabolism markers. This study aimed to investigate the prevalence and risk factors of hyperlipidemia (HL) in patients with MDD who were hospitalized for the first time. METHODS: In this study, we enrolled 981 patients with MDD who were hospitalized for the first time, collected their demographic data and biochemical indicators, and evaluated their clinical symptoms. We divided the patients into HL and non-HL subgroups based on whether they had co-morbid HL. We compared whether there were significant differences between the two groups regarding demographics and general clinical information. RESULTS: A total of 708 of 981 MDD patients were described as being in the hyperlipidemic group, with an incidence of 72.17%. Clinical Global Impression Scale-Severity of Illness (CGI-SI) score and Hamilton Depression Scale (HAMD) score are risk factors for co-morbid HL in patients with MDD. The area under the ROC curve for the CGI-SI and HAMD score and their combined discriminatory ability was approximately 63%, 67%, and 68%, respectively. CONCLUSION: The prevalence of HL was high in patients with MDD who were first hospitalized; Higher HAMD score and CGI-SI score were risk factors for the development of HL in MDD; The HAMD score and the CGI-SI score are predictive of the severity of HL.


Comorbidity , Depressive Disorder, Major , Dyslipidemias , Hospitalization , Humans , Depressive Disorder, Major/epidemiology , Female , Male , Cross-Sectional Studies , Prevalence , Middle Aged , Adult , Risk Factors , Dyslipidemias/epidemiology , Severity of Illness Index , Psychiatric Status Rating Scales
15.
Exp Brain Res ; 242(6): 1507-1515, 2024 Jun.
Article En | MEDLINE | ID: mdl-38719948

Alzheimer's disease is a progressive neurodegenerative disorder characterized by impairments in synaptic plasticity and cognitive performance. Current treatments are unable to achieve satisfactory therapeutic effects or reverse the progression of the disease. Calcineurin has been implicated as part of a critical signaling pathway for learning and memory, and neuronal calcineurin may be hyperactivated in AD. To investigate the effects and underlying mechanisms of FK506, a calcineurin inhibitor, on Alzheimer-like behavior and synaptic dysfunction in the 3 × Tg-AD transgenic mouse model of Alzheimer's disease, we investigated the effect of FK506 on cognitive function and synaptic plasticity in the 3 × Tg-AD transgenic mouse model of Alzheimer's disease. The results showed that FK506 treatment ameliorated cognitive deficits, as indicated by the decreased latency in the water maze, and attenuated tau hyperphosphorylation in 3 × Tg-AD mice. Treatment with FK506 also reduced the levels of certain markers of postsynaptic deficits, including PSD-95 and NR2B, and reversed the long-term potentiation deficiency and dendritic spine impairments in 3 × Tg-AD mice. These findings suggest that treatment with calcineurin inhibitors such as FK506 can be an effective therapeutic strategy to rescue synaptic deficit and cognitive impairment in familial Alzheimer's disease and related tauopathies.


Alzheimer Disease , Calcineurin Inhibitors , Disease Models, Animal , Mice, Transgenic , Tacrolimus , Animals , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Alzheimer Disease/physiopathology , Tacrolimus/pharmacology , Calcineurin Inhibitors/pharmacology , Mice , Maze Learning/drug effects , Maze Learning/physiology , Calcineurin/metabolism , Neuronal Plasticity/drug effects , Neuronal Plasticity/physiology , tau Proteins/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Male , Synapses/drug effects , Synapses/metabolism , Disks Large Homolog 4 Protein/metabolism
16.
J Hazard Mater ; 472: 134501, 2024 Jul 05.
Article En | MEDLINE | ID: mdl-38735182

Rapid advances in machine learning (ML) provide fast, accurate, and widely applicable methods for predicting free radical-mediated organic pollutant reactivity. In this study, the rate constants (logk) of four halogen radicals were predicted using Morgan fingerprint (MF) and Mordred descriptor (MD) in combination with a series of ML models. The findings highlighted that making accurate predictions for various datasets depended on an effective combination of descriptors and algorithms. To further alleviate the challenge of limited sample size, we introduced a data combination strategy that improved prediction accuracy and mitigated overfitting by combining different datasets. The Light Gradient Boosting Machine (LightGBM) with MF and Random Forest (RF) with MD models based on the unified dataset were finally selected as the optimal models. The SHapley Additive exPlanations revealed insights: the MF-LightGBM model successfully captured the influence of electron-withdrawing/donating groups, while autocorrelation, walk count and information content descriptors in the MD-RF model were identified as key features. Furthermore, the important contribution of pH was emphasized. The results of the applicability domain analysis further supported that the developed model can make reliable predictions for query compounds across a broader range. Finally, a practical web application for logk calculations was built.

17.
J Adv Nurs ; 2024 May 24.
Article En | MEDLINE | ID: mdl-38787364

AIMS: The concordance of adolescents with cancer and caregivers was examined, and the core elements of transition readiness were identified. METHODS: In this cross-sectional study, 196 adolescent-caregiver dyads completed the Chinese version of Self-Management and Transition to Adulthood with Rx = Treatment Questionnaire and its parent version between March 2023 and August 2023. Intraclass correlation coefficients, paired t-tests and network analysis were used for data analysis. RESULTS: Caregivers reported slightly lower scores for transition readiness than adolescents (3.28 vs. 3.32). Healthcare engagement and provider communication were core elements in transition readiness networks. At the dyad level, agreement between adolescents' and caregivers' transition readiness ranged from poor to fair (intraclass correlation coefficients 0.103-0.486), and a significant difference in structure was found between the two networks. CONCLUSIONS: Caregivers tended to underestimate adolescents' transition readiness. Attaining better concordance between adolescents and family caregivers is critical to aligning roles and responsibilities in the transition process. IMPLICATIONS FOR PAEDIATRIC CANCER CARE: This study extends the evidence on the variation in adolescents' transition readiness, clarifying the complex associative relationships among the elements of transition readiness, which can be potential pathways for improving transition readiness. Second, this study is the first to assess transition readiness from a dyad's perspective. The findings highlighted the patient-caregiver incongruence in rating patients' transition readiness, suggesting that targeted dyadic interventions should be developed and implemented to improve patient-caregiver transition readiness concordance, facilitate effective communication and mutuality between patients and caregivers, and contribute to their collaboration during the transition of adolescents and optimization of outcomes. WHAT PROBLEM DID THE STUDY ADDRESS?: Increased long-term survival rates of survivors of paediatric cancer highlighted the significant need for care continuity. Transitional readiness is an important predictor of adolescent survivor's ability to adapt to a long-term survival period. Assessments of adolescents' transition readiness are limited and overlook the synergies between family caregivers and adolescents in the transition period. WHAT WERE THE MAIN FINDINGS?: The levels of agreement on rating transition readiness varied from poor to fair among adolescent-caregiver dyads, and caregivers tended to underestimate adolescents' transition readiness. The findings highlighted the patient-caregiver incongruence in rating patients' transition readiness. Targeted dyadic interventions should be developed and implemented to improve patient-caregiver's transition readiness concordance, and facilitate effective communication and mutuality between patients and caregivers. REPORTING METHOD: Study methods and results reported in adherence to the STROBE checklist. PATIENT OR PUBLIC CONTRIBUTION: No patients or members of the public were involved in the study. CONTRIBUTION TO THE WIDER GLOBAL CLINICAL COMMUNITY: The main findings introduce pathways for improving transition readiness, which can enhance healthcare transition among other medical populations.

18.
Contemp Clin Trials ; 142: 107574, 2024 May 18.
Article En | MEDLINE | ID: mdl-38763307

BACKGROUND: Novel and scalable psychotherapies are urgently needed to address the depression and anxiety epidemic. Leveraging artificial intelligence (AI), a voice-based virtual coach named Lumen was developed to deliver problem solving treatment (PST). The first pilot trial showed promising changes in cognitive control measured by functional neuroimaging and improvements in depression and anxiety symptoms. METHODS: To further validate Lumen in a 3-arm randomized clinical trial, 200 participants with mild-to-moderate depression and/or anxiety will be randomly assigned in a 2:1:1 ratio to receive Lumen-coached PST, human-coached PST as active treatment comparison, or a waitlist control condition where participants can receive Lumen after the trial period. Participants will be assessed at baseline and 18 weeks. The primary aim is to confirm neural target engagement by testing whether compared with waitlist controls, Lumen participants will show significantly greater improvements from baseline to 18 weeks in the a priori neural target for cognitive control, right dorsal lateral prefrontal cortex engaged by the go/nogo task (primary superiority hypothesis). A secondary hypothesis will test whether compared with human-coached PST participants, Lumen participants will show equivalent improvements (i.e., noninferiority) in the same neural target from baseline to 18 weeks. The second aim is to examine (1) treatment effects on depression and anxiety symptoms, psychosocial functioning, and quality of life outcomes, and (2) relationships of neural target engagement to these patient-reported outcomes. CONCLUSIONS: This study offers potential to improve the reach and impact of psychotherapy, mitigating access, cost, and stigma barriers for people with depression and/or anxiety. CLINICALTRIALS: gov #: NCT05603923.

19.
Nat Commun ; 15(1): 4303, 2024 May 21.
Article En | MEDLINE | ID: mdl-38773073

Uncontrollable zinc (Zn) plating and hydrogen evolution greatly undermine Zn anode reversibility. Previous electrolyte designs focus on suppressing H2O reactivity, however, the accumulation of alkaline byproducts during battery calendar aging and cycling still deteriorates the battery performance. Here, we present a direct strategy to tackle such problems using a strong Brønsted acid, bis(trifluoromethanesulfonyl)imide (HTFSI), as the electrolyte additive. This approach reformulates battery interfacial chemistry on both electrodes, suppresses continuous corrosion reactions and promotes uniform Zn deposition. The enrichment of hydrophobic TFSI- anions at the Zn|electrolyte interface creates an H2O-deficient micro-environment, thus inhibiting Zn corrosion reactions and inducing a ZnS-rich interphase. This highly acidic electrolyte demonstrates high Zn plating/stripping Coulombic efficiency up to 99.7% at 1 mA cm-2 ( > 99.8% under higher current density and areal capacity). Additionally, Zn | |ZnV6O9 full cells exhibit a high capacity retention of 76.8% after 2000 cycles.

20.
BMC Surg ; 24(1): 163, 2024 May 20.
Article En | MEDLINE | ID: mdl-38769559

BACKGROUND: Abdominal perineal resection (APR) of rectal cancer, also known as Mile's procedure, is a classic procedure for the treatment of rectal cancer. Through the improvement of surgical skills and neoadjuvant therapy, the sphincter-preserving rate in rectal cancer patients has improved, even in patients with ultralow rectal cancer who underwent APR in the past. However, APR cannot be completely replaced by low anterior resection (LAR) in reality. APR still has its indications, when the tumor affects the external sphincter, etc. Good perineal exposure in APR is difficult and can seriously affect surgical safety and the long-term prognosis. METHODS: We reviewed the records of 16 consecutive patients with rectal cancer who underwent APR at Anqing Municipal Hospital from January 2022 to April 2023, including 11 males and 5 females, with an average age of 64.8 ± 10.3 years. The perineal operation was completed with the Lone-Star® retractor-assisted (LSRA) exposure method. After incising the skin and subcutaneous tissue, a Lone-Star® retractor was placed, and the incision was retracted in surrounding directions with 8 small retractors, which facilitated the freeing of deep tissues. We dynamically adjusted the retractor according to the plane to fully expose the surgical field. RESULTS: All 16 patients underwent laparoscopic-assisted APR successfully. Thirteen procedures were performed independently by a single person, and the others were completed by two persons due to intraoperative arterial hemostasis. All specimens were free of perforation and had a negative circumferential resection margin (CRM). Postoperative complications occurred in 4 patients, including urinary retention in 1 patient, pulmonary infection in 1 patient, intestinal adhesion in 1 patient and peristomal dermatitis in 1 patient, and were graded as ClavienDindo grade 3 or lower and cured. No distant metastasis or local recurrence was found for any of the patients in the postoperative follow-up. CONCLUSIONS: The application of the LSRA exposure method might be helpful for perineal exposure during APR for rectal cancer, which could improve intraoperative safety and surgical efficiency, achieve one-person operation, and increase the comfort of operators.


Laparoscopy , Perineum , Proctectomy , Rectal Neoplasms , Humans , Rectal Neoplasms/surgery , Male , Female , Middle Aged , Perineum/surgery , Laparoscopy/methods , Aged , Proctectomy/methods , Retrospective Studies , Treatment Outcome
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