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 evaluate the clinical efficacy and safety of tri-mebutine combined with Shugan granule in the treatment of functional dyspepsia.Methods A total of 84 patients with functional dyspepsia were randomly divided into control group ( n=42 ) and treatment group ( n=42 ).Control group was treated with trimebutine 0.2 g, tid for 4 weeks.Treatment group was treated with trimebutine 0.2 g, tid and Shu-gan granule 3 g, bid for 4 weeks.The clinical symptom scores, self -rating anxiety scale ( SAS ) and self -rating depression scale ( SDS ) scores, and incidence of adverse drug reactions were compared between the two groups.Results After treatment, the clinical symptom scores, SAS and SDS scores in treatment group were significantly lower than those in control group( all P<0.05).The incidence of adverse drug reactions in two groups has no significant difference( P>0.05).Conclusion The combined therapy of trimebutine and Shugan granule can significantly improve the clinical symptoms and the states of anxiety and depression without increasing of the incidence of adverse drug reactions.

OBJECTIVETo investigate the significance of apolipoprotein (Apo)-A1 in urine as a biomarker for early diagnosis and classification of bladder urothelial carcinoma (BUC).

METHODSUrine samples were divided into four groups: normal control group, benign bladder disease group, low-grade malignant BUC group, and high-grade malignant BUC group. Apo-A1, which showed significantly different expression among the four groups, was selected according to the two-dimensional electrophoresis (2-DE) images of the four groups, and enzyme-linked immunosorbent assay (ELISA) was used to quantify Apo-A1 in the four groups. A receiver operating characteristic (ROC) curve was generated, and the optimal operating points on the ROC curve were found to determine the critical concentrations of Apo-A1 for early diagnosis of BUC and differentiation of low-grade and high-grade malignant BUC. The results were verified clinically, and the specificity and sensitivity were calculated.

RESULTSThe 2-DE images showed that that the level of Apo-A1 increased from the normal control grouP to high-grade malignant BUC group. The ELISA showed that there was no significant difference in Apo-A1 level between the normal control grouP and benign bladder disease group, but the Apo-A1 level was significantly higher in the BUC groups than in the normal control grouP and benign bladder disease grouP (P < 0.01); the high-grade BUC grouP had a significantly higher Apo-A1 level than the low-grade BUC grouP (P < 0.01). The BUC patients and those without BUC could be differentiated with an Apo-A1 concentration of 18.22 ng/ml, while the low-grade and high-grade malignant BUC could be differentiated with an Apo-A1 concentration of 29.86 ng/ml. When used as a biomarker, Apo-A1 had a sensitivity of 91.6% (98/107) and a specificity of 85.7% (42/49) for diagnosis of BUC and had a sensitivity of 83.7% (41/49) and a specificity of 89.7% (52/58) for BUC classification.

CONCLUSIONApo-A1 may be a biomarker for early diagnosis and classification of BUC and shows promise for clinical application.

Aged ; Apolipoprotein A-I ; urine ; Early Detection of Cancer ; Female ; Humans ; Male ; Middle Aged ; Urinary Bladder Neoplasms ; diagnosis ; urine

BACKGROUNDLaparoscopic dismembered pyeloplasty is technically feasible for ureteropelvic junction (UPJ) obstruction although it is still challenged by its technical difficulty and time-consuming. In this study, we compared the initial results of retroperitoneal laparoscopic pyeloplasty versus a combined laparoscopic dissection and open reconstruction through a small incision in the treatment of UPJ obstruction.

METHODSSixty-four patients with primary UPJ obstruction underwent pyeloplasty: 32 patients underwent laparoscopic procedure and 32 patients underwent open assisted laparoscopic surgery including two steps, ie, laparoscopic dissection of the UPJ transperitoneally and then pyeloplasty via an extended small incision. The demographic data and intraoperative, postoperative and follow-up conditions of patients were compared between the two groups.

RESULTSPreoperative data were comparable in the patients of the two groups. The operative time was shorter (60.9 minutes vs 157.7 minutes, P < 0.0001) and the complication rate was lower (9.4% vs 31.3%, P < 0.05) in the open assisted group than in the laparoscopic group. The estimated blood loss (42.3 ml vs 47.8 ml), time to have normal diet (37.6 hours vs 33.8 hours), and hospital stay (6.7 days vs 6.2 days) were equivalent. The operative success rate was 97% for the open assisted group and 91% for the laparoscopic group.

CONCLUSIONSThe procedure of combined small incision with laparoscopy for UPJ obstruction is technically easy, and the results are promising. It can be used as an alternative to conventional procedures.

Adolescent ; Adult ; Child ; Female ; Humans ; Kidney Pelvis ; surgery ; Laparoscopy ; methods ; Male ; Middle Aged ; Postoperative Complications ; epidemiology ; Retroperitoneal Space ; Ureteral Obstruction ; surgery ; Urologic Surgical Procedures

BACKGROUNDA five-year follow-up study of intensive multifactorial intervention was undertaken to assess the changes of circulating serum amyloid A (SAA) levels and the incidence of atherosclerosis (AS) in patients with short-duration type 2 diabetes mellitus (T2DM) without macroangiopathy, and whether intensive multifactorial intervention could prevent or at least postpone the occurrence of macroangiopathy.

METHODSAmong 150 patients with short-duration T2DM, 75 were assigned to receive conventional outpatient treatment (conventional group) and the others underwent intensive multifactorial integrated therapy targeting hyperglycemia, hypertension, dyslipidemia and received aspirin simultaneously (intensive group).

RESULTSPlasma SAA levels were higher in diabetic patients than those in healthy control subjects, and decreased obviously after intensive multifactorial intervention. The levels of SAA were positively correlated with body mass index (BMI), waist hip ratio (WHR), triglyceride (TG), high sensitive C-reactive protein (hs-CRP) and common carotid intima-media thickness (CC-IMT). The standard-reaching rates of glycemia, blood pressure and lipidemia were significantly higher in intensive group than those of conventional group. The incidence of macroangiopathy decreased by 58.96% in intensive group compared with conventional group.

CONCLUSIONSIntensive multifactorial intervention may significantly reduce the SAA levels and prevent the occurrence of AS in short-duration patients with T2DM. SAA might be one of the risk factors of T2DM combined with AS.

Adult ; Aged ; Antihypertensive Agents ; pharmacology ; therapeutic use ; Blood Glucose ; metabolism ; C-Reactive Protein ; metabolism ; Diabetes Mellitus, Type 2 ; complications ; drug therapy ; metabolism ; Diabetic Angiopathies ; etiology ; Female ; Humans ; Hypoglycemic Agents ; pharmacology ; therapeutic use ; Hypolipidemic Agents ; pharmacology ; therapeutic use ; Male ; Middle Aged ; Multivariate Analysis ; Serum Amyloid A Protein ; metabolism ; Triglycerides ; blood ; Tunica Media ; drug effects

Background A five-year follow-up study of intensive multifactorial intervention was undertaken to assess the changes of circulating serum amyloid A(SAA)levels and the incidence of atherosclerosis(AS)in patients with short-duration type 2 diabetes mellitus(T2DM)without maoroangiopathy,and whether intensive multifactorial intervention could prevent or at least postpone the occurence of macroangiopathy.Methods Among 150 patients with short-duration T2DM,75 were assigned to receive conventional outpatient treatment (conventional group)and the others underwent intensive multifactorial integrated therapy targeting hyperglycemia,hypertension,dyslipidemia and received aspirin simultaneously(intensive group).Results Plasma SAA levels were higher in diabetic patients than those in healthy control subjects,and decreased obviously after intensive multifactorial intervention.The levels of SAA were positively correlated with body mass index(BMI),waist hip ratio(WHR),triglyceride(TG),high sensitive C-reactive protein(hs-CRP)and common carotid intima-media thickness(CC-IMT).The standard-reaching rates of glycemia,blood pressure and lipidemia were significantly higher in intensive group than those of conventional group.The incidence of macroangiopathy decreased by 58.96% in intensive group compared with conventional group.Conclusions Intensive multifactorial intervention may significantly reduce the SAA levels and prevent the occurrence of AS in short-duration patients with T2DM.SAA might be one of the risk factors of T2DM combined with AS.

OBJECTIVETo study the effect of 70 degrees recumbent position transperitoneal laparoscopy for treatment of upper urinary tract transitional cell carcinoma (TCC).

METHODSFrom May 2004 to January 2007, 70 degrees recumbent position transperitoneal laparoscopy combined with urethral resectoscope was used to treat 31 cases of upper urinary tract transitional cell carcinoma. At the same time titanium clip to occlude the two extremities of ureter tumor was used, extracting specimen by oblique incision of lower quadrant.

RESULTSAll operations were finished successfully, no one was turned to open surgery; mean operation time was 140 min, mean blood loss 80 ml, mean hospital stay time 8 d, without complications of urine leakage and intestinal fistula and so on.

CONCLUSIONS70 degrees recumbent position transperitoneal laparoscopy for resection of whole kidney and ureter is worth of general clinical application because it could provide large space for operation, simplify the treatment of renal pedicle vessels, decrease operation risk, reduce operation trauma and offer early recovery. But its effect on tumor spread and recurrence will still need long term follow-up.

Adult ; Aged ; Carcinoma, Transitional Cell ; surgery ; Female ; Follow-Up Studies ; Humans ; Laparoscopy ; methods ; Male ; Middle Aged ; Posture ; Treatment Outcome ; Ureteral Neoplasms ; surgery ; Urinary Bladder Neoplasms ; surgery

OBJECTIVETo report initial experience with laparoscopic radical cystectomy in 43 patients with invasive bladder carcinoma.

METHODSFrom December 2003 to October 2006, 29 men and 14 women underwent laparoscopic radical cystectomy with extracorporeal-assisted urinary diversion for transitional cell carcinoma of the bladder (n=40), adenocarcinoma (n=2) and squamous cell arcinoma (n=1). We report the specific technical details and present initial results of our series.

RESULTSThe mean operative time of laparoscopic radical cystectomy with pelvic lymph node dissection was 195.4 min, the mean blood loss 273.7 ml, and the transfusion rate 6.9%. Two procedures converted to open techniques. Lymphadenectomy detected lymph node metastasis in three patients.

CONCLUSIONSWe demonstrate that the combination of laparoscopic radical cystectomy and extracorporeal urinary diversion is possible and remains a safe, feasible, and repeatable surgical technique. The laparoscopic surgery with extracorporeal urinary reconstruction is emerging as a viable alternative to open radical cystectomy while characterized by less trauma, short recovery time and low complications. Intermediate oncologic outcomes are encouraging and comparable to those of open series. To determine the oncologic outcome long-time follow-up will be necessary.

Aged ; Cystectomy ; methods ; Female ; Follow-Up Studies ; Humans ; Laparoscopy ; Male ; Middle Aged ; Treatment Outcome ; Urinary Bladder Neoplasms ; surgery ; Urinary Diversion ; methods

BACKGROUNDTanis was reported as a putative receptor for serum amyloid A (SAA) involving glucose regulated protein in insulin regulated resistance. It was found to be dysregulated in diabetic rats (Psammomys obesus, Israeli sand rat) and its homologue for humans is SelS/AD-015. The present study analyzed mRNA expression of SelS in omental adipose tissue biopsies from patients with type 2 diabetes mellitus (T2DM), and age- and weight-matched nondiabetic patients, the relationship of SelS mRNA with Homa-IR and serum SAA level.

METHODSHuman omental adipose tissues from ten cases of type 2 diabetic patients and twelve cases of nondiabetic individuals were analyzed for the expression level of SelS mRNA by semiquantitative polymerase chain reaction (PCR), Homa-IR estimated by standard formula and SAA level by enzyme-linked immunosorbent assay (ELISA).

RESULTSSelS mRNA expression, Homa-IR and serum SAA were higher in T2DM sufferers than in nondiabetic control group. SelS mRNA level was positively correlated with Homa-IR and SAA level in each group.

CONCLUSIONSSelS protein may be involved in insulin resistance in Chinese with T2DM by acting as the SAA receptor, thus playing an important role in the development of T2DM and atherosclerosis.

Adipose Tissue ; metabolism ; Adult ; Aged ; Base Sequence ; Diabetes Mellitus, Type 2 ; metabolism ; Female ; Humans ; Insulin Resistance ; Male ; Membrane Proteins ; genetics ; Molecular Sequence Data ; Omentum ; metabolism ; RNA, Messenger ; analysis ; Selenoproteins ; genetics ; Serum Amyloid A Protein ; analysis

Adult ; Female ; Humans ; Kidney Transplantation ; Laparoscopy ; methods ; Living Donors ; Male ; Middle Aged ; Nephrectomy ; methods