The structures and activities of enzymes are influenced by pH of the environment. Understanding and distinguishing the adaptation mechanisms of enzymes to extreme pH values is of great significance for elucidating the molecular mechanisms and promoting the industrial applications of enzymes. In this study, the ESM-2 protein language model was used to encode the secreted microbial proteins with the optimal performance above pH 9 and below pH 5, which yielded 47 725 high-pH protein sequences and 66 079 low-pH protein sequences, respectively. A deep learning model was constructed to identify protein acid-base tolerance based on amino acid sequences. The model showcased significantly higher accuracy than other methods, with the overall accuracy of 94.8%, precision of 91.8%, and a recall rate of 93.4% on the test set. Furthermore, we built a website (https://enzymepred.biodesign.ac.cn), which enabled users to predict the acid-base tolerance by submitting the protein sequences of enzymes. This study has accelerated the application of enzymes in various fields, including biotechnology, pharmaceuticals, and chemicals. It provides a powerful tool for the rapid screening and optimization of industrial enzymes.
Deep Learning ; Hydrogen-Ion Concentration ; Amino Acid Sequence ; Enzymes/metabolism* ; Sequence Analysis, Protein ; Proteins/metabolism* ; Bacterial Proteins/metabolism*

Objective To observe the bone metabolism of psoriatic arthritis (PsA) and investigate the roles of some bone metabolism markers such as tartrate-resistant acid phosphatase 5b (TRACP5),C-terminal telopeptide of collagen-Ⅰ (CTX-Ⅰ) and BALP in PsA patients with bone destructions.Methods Sixty-five cases of psoriatic arthritis,30 cases of psoriasis and 30 cases of healthy people were enrolled.Bone mineral densities of lumbar spines and the left femoral necks were measured for all PsA patients using dual energy X-ray absorptiometry.The Serum levels of TRACP5b,CTX-Ⅰ,BALP of healthy controls,Ps and PsA patients were measured.The PsA group was further divided into bone destruction group and none bone destruction group by image datasets.The levels of TRACP5b,CTX-Ⅰ,BALP,PsAJAI,ESR and CRP from each group were detected.Mann-Whitney and x2 test were used for statistic analysis.Results TRACP5b levels of the healthy controls,Ps and PsA patients were (0.9±0.4),(0.7±0.5) and (2.0±1.4) U/L respectively,and were significantly higher in the PsA patients than those of the other two groups (Z=-3.698,-3.638; P＜0.05).The CTX-Ⅰ levels of these three groups were (0.9±0.8),(0.6±0.7) and (2.6±1.8) ng/ml respectively,and were also dramatically higher in the PsA patients than the other two groups (Z=-5.262,-5.734; P＜0.05).BALP levels of each group were (22±4),(22±4) and (25±7) U/L,and were also evidently higher in the PsA patients than patients in the other two groups (Z=-2.214,-2.000; P＜0.05).Meanwhile,the levels of TRACP5b [(2.6±1.4) U/L],CTX-Ⅰ [(3.1±1.8) ng/ml] and BALP [(26±7) U/L] were significantly higher in bone destruction group than those in the none bone destruction group [(1.2±1.0) U/L,(1.9±1.6) ng/ml,(23±6) U/L,Z=-3.544,-3.429,-2.083; P＜0.05].Conclusion The high levels of TRACP5b,CTX-Ⅰ and BALP in PsA indicate that there is bone metabolism imbalances in PsA.And the high levels of TRACP5b,CTX-Ⅰ and BALP in the bone destruction group suggest that the rises of TRACP5,CTX-Ⅰ and BALP levels may be related with bone erosions.

ObjectiveTo explore the effect of osteoclasts and osteoprotegerin/receptor activator of nuclear factor-kappa B ligand (OPG/RANKL) system on bone destruction of psoriatic arthritis.MethodsThe peripheral blood mononuclear cells from 41 psoriatic arthritis (PsA) patients,20 osteoarthritis (OA) patients and 24 healthy controls were cultured to become osteoclasts.After 14 days,cytochemistry method was used to detect tartrate-resistant acid phosphatase (TRAP) expression.At the same time,enzyme-linked immuno sorbent assay(ELISA) was used to measure the levels of serum OPG and RNAKL for all cases.At the same time,the clinical and laboratory examinations of the PsA were collected.Statistical analysis was conducted with one-way ANOVA and Spearman's correlation.ResultsSignificantly higher OC production was observed in the peripheral blood of PsA patients[(17.7±4.8)/view field] than that of the healthy controls[(6.4±1.6)/view field] and OA patients [(6.5±l.6)/view field].The levels of RANKL were significantly higher in PsA patients [(178±38) pg/ml] than those in the other two groups [(32±4) pg/ml and (67±17) pg/ml].There was significant difference between the PsA group with bone destruction and without destruction in the levels of OC and RANKL [(17.6±0.9) /view vs(7.9±1.3) /view and(199±72) pg/ml vs(128±44) pg/ml,P＜0.01].Imaging scores was positively correlated with the levels of OC and RANKL in PsA patients (P＜0.05).ConclusionIn PsA,there are significantly more OC and higher RANKL in the peripheral blood than those of the controls.The high levels of OC and RANKL are closely related with bone destruction.OC and RANKL are useful in identifying bone destruction.

Objective To study the influence of PYLL on life span of residents. Methods The reduce of potential life span in Kunshan residents from 1982～1999 was analysed between the male and female. Results The life span reduced significantly in injury, poisoning and c ancer, which accounted for over 56% of total causes o f death in PYLL, especially, over 60 % in male. PYLL rate in male was higher than that in female. PYLL rate in male a nd female (except brain blood vessel disease) from 1991～1999 was lower than tha t from 1982～1990. It was consistent with increasing of old age population pr oport ion and prolonging of expected life span in Kunshan residents year by year. Conclusions The reasons that causes to death of residents were injury a nd poisoning and cancer.