The translation of genetic findings from genome-wide association studies into actionable therapeutics persists as a critical challenge in Alzheimer's disease (AD) research. Here, we present PI4AD, a computational medicine framework that integrates multi-omics data, systems biology, and artificial neural networks for therapeutic discovery. This framework leverages multi-omic and network evidence to deliver three core functionalities: clinical target prioritisation; self-organising prioritisation map construction, distinguishing AD-specific targets from those linked to neuropsychiatric disorders; and pathway crosstalk-informed therapeutic discovery. PI4AD successfully recovers clinically validated targets like APP and ESR1, confirming its prioritisation efficacy. Its artificial neural network component identifies disease-specific molecular signatures, while pathway crosstalk analysis reveals critical nodal genes (e.g., HRAS and MAPK1), drug repurposing candidates, and clinically relevant network modules. By validating targets, elucidating disease-specific therapeutic potentials, and exploring crosstalk mechanisms, PI4AD bridges genetic insights with pathway-level biology, establishing a systems genetics foundation for rational therapeutic development. Importantly, its emphasis on Ras-centred pathways-implicated in synaptic dysfunction and neuroinflammation-provides a strategy to disrupt AD progression, complementing conventional amyloid/tau-focused paradigms, with the future potential to redefine treatment strategies in conjunction with mRNA therapeutics and thereby advance translational medicine in neurodegeneration.

BackgroundDepression presents a significant risk to the physical and mental health of the elderly. The relationship between sleep and depressive symptoms has become a major research focus. However， previous research findings on this relationship have yielded inconsistent conclusions. ObjectiveTo explore the relationship between sleep duration and depressive symptoms in the elderly， in order to provide insights into the prevention of depressive symptoms and delaying their progression in the elderly. MethodsData analysis involved 8 210 adults aged 60 years or older， utilizing data from the 2018 China Health and Retirement Longitudinal Study （CHARLS） survey. Participants were categorized into two groups those with depressive symptoms and those without- based on the Center for Epidemiologic Studies Depression-10 Scale （CESD-10） criteria. Logistic regression and restricted cubic spline models were used to analyze the association between sleep duration and depressive symptoms. ResultsThe 318 people with depressive symptoms were detected among the 8 210 elderly participants， with an average sleep duration of （6.14±2.05） hours per night. Restricted cubic spline models showed a non-linear association between sleep duration and depressive symptoms （χ²=412.670，P<0.01）. After adjusting for confounding factors， compared to the elderly with a sleep duration 7~7.9 hours， the risk of depressive symptoms in the elderly was 2.971 times higher （95% CI： 2.560~3.449， P<0.01） in those with a sleep duration <6 hours， 1.372 times higher （95% CI： 1.161~1.621， P<0.01） in those with 6~6.9 hours， and 1 185 times higher （95% CI： 1.009~1.393， P<0.05） in those with ≥8 hours. Subgroup analysis showed no correlation between sleep duration ≥8 hours and the risk of depressive symptoms across genders and the 60~69 age group （P>0.05）. ConclusionThere was an approximately nonlinear association between sleep duration and depressive symptoms， with differences by gender and age.［Funded by Sichuan Applied Psychology Research Center， Chengdu Medical College （number， CSXL-22226）］

Objective:To investigate the correlation between serum thyroglobulin antibody (TG-Ab) and thyroid peroxidase antibody (TPO-Ab) cconcentrations and arteriosclerosis development in middle-aged and older adult patients with depression.Methods:A total of 200 middle-aged and older adult patients with depression who received treatment in the Third People's Hospital of Huzhou from January 2018 to October 2019 were included in this study. They were divided into four groups ( n = 50/group) according to TG-Ab and TPO-Ab test results: TG-Ab-positive (group 1), TPO-Ab-positive (group 2), TG-Ab-positive and TPO-Ab-positive (group 3), TG-Ab-negative and TPO-Ab-negative (control group). Serum thyroid hormone level, ankle-brachial pressure index (ABI), brachial-ankle pulse wave velocity, and the incidences of intima-media thickening and plaque formation in the lower extremity arteries were compared between groups. Results:Total thyroxine concentration in the control group, groups 1, 2 and 3 was (89.96 ± 2.45) nmol/L, (101.29 ± 3.35) nmol/L, (90.09 ± 2.70) nmol/L, (97.55 ± 2.57) nmol/L, respectively. There was a significant difference in total thyroxine concentration between groups ( F = 3.85, P < 0.05). Brachial-ankle pulse wave velocity in the control group, groups 1, 2, and 3 was (1 327.55 ± 67.78) cm/s, (1 510.36 ± 83.05) cm/s, (1 422.71 ± 71.40) cm/s, (1 533.95 ± 87.01) cm/s, respectively. There was a significant difference in brachial-ankle pulse wave velocity between groups ( F = 65.12, P < 0.05). The incidence of intima-media thickening in the control group, groups 1, 2, and 3 was 18% (9/50), 50% (25/50), 32% (16/50), 60% (30/50), respectively. The incidence of plaque formation in the control group, groups 1, 2, and 3 was 22% (11/50), 56% (28/50), 40% (20/50), 70% (35/50), respectively. There were significant differences in intima-media thickening and plaque formation between groups ( χ2 = 21.83, 25.77, all P < 0.001). Logistic multivariate regression analysis showed that age ( OR = 0.953) and TG-Ab ( OR = 1.116) were independent risk factors for developing arteriosclerosis in middle-aged and older adult patients with depression ( P < 0.05). Conclusion:TG-Ab-positive results are an independent risk factor for developing arteriosclerosis in middle-aged and older adult patients with depression. TPO-Ab-positive results have a synergistic effect on the occurrence and development of arteriosclerosis in middle-aged and older adult patients with depression. Monitoring serum TG-Ab and TPO-Ab concentrations is of great clinical significance for the prevention and treatment of arteriosclerosis in middle-aged and older adult patients with depression.

Objective: The role of planned neoadjuvant radiotherapy or chemoradiotherapy in the non-radical resection of esophageal squamous cell carcinoma was unclear. The study aimed to evaluate their therapeutic effect and analyze the prognostic factors. Methods: We retrospectively analyzed the clinical data of locally advanced esophageal squamous cell carcinoma who received neoadjuvant radio therapy (33 patients) and concurrent chemoradiotherapy (119 patients) from January 2004 to December 2016 in our single-institution database.The survival rates were calculated by Kaplan-Meier method. The prognostic factors were analyzed by using Log rank test and Cox proportional hazards model. Results: The median follow-up was 29.8 months. One hundred and one patients survived more than 3 years. The rates of overall survival (OS) and disease-free survival (DFS) at 3 years were 63.9% and 55.6%, respectively.The rates of complete, partial and minimal pathological response of the primary tumor were 50.3%, 38.4%, 11.3%, the corresponding 3-year OS were 75.5%, 57.4%, 27.3% (P<0.001) and 3-year DFS were 72.0%, 44.7%, 17.6% (P<0.001), respectively.The postoperative lymph node metastasis rate was 27.0%. The 3-year OS and DFS of the lymph node positive group was 45.6% and 32.8%, significantly lower than 70.8% and 63.7% of the negative group (both P<0.001). The 3-year OS and DFS of pathologic stage Ⅰ, Ⅱ, ⅢA, ⅢB and Ⅵ A were 76.2%, 57.4%, 64.7%, 35.0%, 33.3% (P<0.001) and 70.1%, 49.3%, 41.2%, 22.1%, 33.3% (P<0.001), respectively.The operation-related mortality was 3.3%. Multivariate analysis showed that chest pain, postoperative respiratory failure, pathological differentiation, more than 15 lymph node dissection and ypTNM stage were the independent prognostic factors of OS (P<0.05 for all). Conclusions The planned neoadjuvant radiotherapy or chemoradiotherapy for the non-radical resection of advanced esophageal squamous cell carcinoma could result in favorable survival. The chest pain, postoperative respiratory failure, pathological differentiation, the number of lymph node resection and ypTNM stage are the independent prognostic factors of the prognosis of these patients.

Natural lignocellulosic materials contain cellulose, hemicellulose, and lignin. Cellulose hydrolysis to glucose requires a series of lignocellulases. Recently, the research on the synergistic effect of lignocellulases has become a new research focus. Here, four lignocellulase genes encoding β-glucosidase, endo-1,4-β-glucanase, xylanase and laccase from termite and their endosymbionts were cloned into pETDuet-1 and pRSFDuet-1 and expressed in Escherichia coli. After SDS-PAGE analysis, the corresponding protein bands consistent with the theoretical values were observed and all the proteins showed enzyme activities. We used phosphoric acid swollen cellulose (PASC) as substrate to measure the synergistic effect of crude extracts of co-expressing enzymes and the mixture of single enzyme. The co-expressed enzymes increased the degradation efficiency of PASC by 44% compared with the single enzyme mixture; while the degradation rate increased by 34% and 20%, respectively when using filter paper and corn cob pretreated with phosphoric acid as substrates. The degradation efficiency of the co-expressed enzymes was higher than the total efficiency of the single enzyme mixture.
Animals ; Cellulase ; Cellulose ; Hydrolysis ; Isoptera ; Lignin ; Symbiosis ; beta-Glucosidase

Objective The role of planned neoadjuvant radiotherapy or chemoradiotherapy in the non?radical resection of esophageal squamous cell carcinoma was unclear. The study aimed to evaluate their therapeutic effect and analyze the prognostic factors. Methods We retrospectively analyzed the clinical data of locally advanced esophageal squamous cell carcinoma who received neoadjuvant radio therapy ( 33 patients) and concurrent chemoradiotherapy (119 patients) from January 2004 to December 2016 in our single?institution database.The survival rates were calculated by Kaplan?Meier method. The prognostic factors were analyzed by using Log rank test and Cox proportional hazards model. Results The median follow?up was 29.8 months. One hundred and one patients survived more than 3 years. The rates of overall survival (OS) and disease?free survival ( DFS) at 3 years were 63.9% and 55.6%, respectively.The rates of complete, partial and minimal pathological response of the primary tumor were 50.3%, 38.4%, 11.3%, the corresponding 3?year OS were 75.5%, 57.4%, 27.3%( P＜0.001) and 3?year DFS were 72.0%, 44.7%, 17.6%(P＜0.001), respectively.The postoperative lymph node metastasis rate was 27.0%. The 3?year OS and DFS of the lymph node positive group was 45.6% and 32.8%, significantly lower than 70.8% and 63.7%of the negative group (both P＜0.001).The 3?year OS and DFS of pathologic stage Ⅰ,Ⅱ,ⅢA,ⅢB andⅥ A were 76.2%, 57.4%, 64.7%, 35.0%, 33.3%( P＜0.001) and 70.1%, 49.3%, 41.2%, 22.1%, 33.3%(P＜0.001), respectively.The operation?related mortality was 3.3%. Multivariate analysis showed that chest pain, postoperative respiratory failure, pathological differentiation, more than 15 lymph node dissection and ypTNM stage were the independent prognostic factors of OS ( P＜0.05 for all). Conclusions The planned neoadjuvant radiotherapy or chemoradiotherapy for the non?radical resection of advanced esophageal squamous cell carcinoma could result in favorable survival. The chest pain, postoperative respiratory failure, pathological differentiation, the number of lymph node resection and ypTNM stage are the independent prognostic factors of the prognosis of these patients.

Objective The role of planned neoadjuvant radiotherapy or chemoradiotherapy in the non?radical resection of esophageal squamous cell carcinoma was unclear. The study aimed to evaluate their therapeutic effect and analyze the prognostic factors. Methods We retrospectively analyzed the clinical data of locally advanced esophageal squamous cell carcinoma who received neoadjuvant radio therapy ( 33 patients) and concurrent chemoradiotherapy (119 patients) from January 2004 to December 2016 in our single?institution database.The survival rates were calculated by Kaplan?Meier method. The prognostic factors were analyzed by using Log rank test and Cox proportional hazards model. Results The median follow?up was 29.8 months. One hundred and one patients survived more than 3 years. The rates of overall survival (OS) and disease?free survival ( DFS) at 3 years were 63.9% and 55.6%, respectively.The rates of complete, partial and minimal pathological response of the primary tumor were 50.3%, 38.4%, 11.3%, the corresponding 3?year OS were 75.5%, 57.4%, 27.3%( P＜0.001) and 3?year DFS were 72.0%, 44.7%, 17.6%(P＜0.001), respectively.The postoperative lymph node metastasis rate was 27.0%. The 3?year OS and DFS of the lymph node positive group was 45.6% and 32.8%, significantly lower than 70.8% and 63.7%of the negative group (both P＜0.001).The 3?year OS and DFS of pathologic stage Ⅰ,Ⅱ,ⅢA,ⅢB andⅥ A were 76.2%, 57.4%, 64.7%, 35.0%, 33.3%( P＜0.001) and 70.1%, 49.3%, 41.2%, 22.1%, 33.3%(P＜0.001), respectively.The operation?related mortality was 3.3%. Multivariate analysis showed that chest pain, postoperative respiratory failure, pathological differentiation, more than 15 lymph node dissection and ypTNM stage were the independent prognostic factors of OS ( P＜0.05 for all). Conclusions The planned neoadjuvant radiotherapy or chemoradiotherapy for the non?radical resection of advanced esophageal squamous cell carcinoma could result in favorable survival. The chest pain, postoperative respiratory failure, pathological differentiation, the number of lymph node resection and ypTNM stage are the independent prognostic factors of the prognosis of these patients.

Cellulose hydrolysis to glucose requires a series of cellulase enzymes, of which β-glucosidases play a crucial role. β-glucosidase (MbmgBG1) derived from the midgut of Macrotermes barneyi has higher glucose tolerance (maintaining more than 60% enzyme activity at 1.5 mol/L glucose). However, low enzyme activity and poor thermal stability limit the applications of β-glucosidase in food industries. Point mutants (F167L, T176C, E347I, R354K, N393G and V425M) were obtained by site-directed mutagenesis of non-conserved amino acids near conserved amino acids. Among them, the specific activities against to substrate pNPG of two mutants (F167L and R354K) were about 2-fold and 4-fold higher than that of MbmgBG1. Kcat/Km values were also higher than that of the wild-type, reflecting stronger affinity to the substrate and higher catalytic ability of mutants than MbmgBG1. When the glucose concentration was 1.5 mol/L, the enzyme activity of MbmgBG1 was about 60% of the original activity. F167L and R354K kept 60% enzymatic activity when the glucose concentrations of was 2.0 mol/L and 3.0 mol/L, respectively. These results lay a foundation for further studies on the catalytic efficiency of β-glucosidase.

Laccases are enzymes belonging to the group of multi-copper oxidases. These enzymes are widely distributed in insects, plants, fungi and bacteria. In general, laccases can oxidize an exceptionally high number of substrates, so they have broad applications in textile, pulp, food and the degradation of lignin. However, low yield, low activity and thermo-instability of laccase in nature limit the application of laccase. High efficient heterologous expression of the protein is an effective way for solving this problem. Here, we summarize the research advances of heterologous expression of eukaryote-origin laccases. We focus on the overexpression of eukaryote-origin laccases using different expression system and the method for improving the production yield and enzyme activity in yeast cells. Information provided in this review would be helpful for researchers in the field.

Objective:To evaluate therapeutic effects and adverse reactions of tocilizumab on patients with severe active rheumatoid arthritis (RA).Methods:Twelve patients with severe refractory RA were treated with tocilizumab.The clinical and laboratory indices and the side effects were recorded after treatment.Results:The clinical and laboratory indices and the disease activity score 28 (DAS28) were observed in all patients,which were significantly improved after TCZ therapy (P＜0.05),and no obvious adverse reactions were found.Conclusion:Tocilizumab can effectively relieve the symptoms and improve the conditions of severe active RA.