Self-organized blastoids from extended pluripotent stem (EPS) cells possess enormous potential for investigating postimplantation embryo development and related diseases. However, the limited ability of postimplantation development of EPS-blastoids hinders its further application. In this study, single-cell transcriptomic analysis indicated that the "trophectoderm (TE)-like structure" of EPS-blastoids was primarily composed of primitive endoderm (PrE)-related cells instead of TE-related cells. We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure. Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation. Furthermore, we demonstrated that blastocyst-like structures reconstituted by combining the EPS-derived bilineage embryo-like structure (BLES) with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses. In summary, our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.
Pregnancy ; Female ; Animals ; Mice ; Tetraploidy ; Blastocyst ; Embryo, Mammalian ; Cell Differentiation ; Embryonic Development

Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity.Herein,choline metabolism was discovered by spatially resolved metab-olomics analysis as metabolic vulnerability which is highly active in different cancer types,and a choline-modified strategy for small molecule-drug conjugates(SMDCs)design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy,instead of directly inhibiting choline metabolism.As a proof-of-concept,choline-modified SMDCs were designed,screened,and investigated for their druggability in vitro and in vivo.This strategy improved tumor targeting,preserved tumor inhibition and reduced toxicity of paclitaxel,through targeted drug delivery to tumor by highly expressed choline transporters,and site-specific release by carboxylesterase.This study expands the strategy of targeting metabolic vulnerability and provides new ideas of devel-oping SMDCs for precise cancer therapy.

Tumors are spatially heterogeneous tissues that comprise numerous cell types with intricate structures.By interacting with the microenvironment,tumor cells undergo dynamic changes in gene expression and metabolism,resulting in spatiotemporal variations in their capacity for proliferation and metastasis.In recent years,the rapid development of histological techniques has enabled efficient and high-throughput biomolecule analysis.By preserving location information while obtaining a large number of gene and molecular data,spatially resolved metabolomics(SRM)and spatially resolved transcriptomics(SRT)approaches can offer new ideas and reliable tools for the in-depth study of tumors.This review provides a comprehensive introduction and summary of the fundamental principles and research methods used for SRM and SRT techniques,as well as a review of their applications in cancer-related fields.

Objective:To investigate the long-term efficacy and complications of augmentation uretero-enterocystoplasty (AUEC).Methods:The clinical data of 262 patients with lower urinary tract dysfunction who underwent AUEC at our center from January 2003 to June 2022 were analyzed retrospectively. There were 193 males and 69 females, the median age was 24 (4, 67) years, the median disease duration was 12.0 (0.2, 56.0) years and the preoperative creatinine was 91.5 (68.1, 140.0) μmol/L. 320 ureters had high-grade UUTD, 216 ureters had VUR, 14 of which had low-pressure reflux.The number of low-grade VUR ureter was 22 (10.2%) and the number of high-grade VUR ureter was 194 (89.8%). Video-urodynamics showed that the maximum bladder capacity was 102 (47, 209) ml, the maximum detrusor pressure was 33.0 (15.5, 50.5) cmH 2O, and the bladder compliance was 6.4 (3.0, 12.3) ml/cmH 2O. All patients underwent AUEC. The surgical method is to cut a segment of sigmoid colon, open the sigmoid colon along the mesenteric margin, fold and suture it into " U" or " S" shaped intestinal mesh according to the principle of " detubulization" . At the same time, perform ureteroplasty and replanting, and then anastomosis the intestinal mesh with the opened bladder flap to form an expanded new bladder. Follow-up was performed via outpatient clinic or telephone. The creatinine, maximum bladder capacity, maximum detrusor pressure, bladder compliance, ureteral reflux and upper urinary tract dilatation were compared preoperatively and postoperatively. The postoperative complications were also evaluated. Results:The median follow-up time was 57.4 (4, 151) months after surgery. At 1-3 months after surgery, the maximum bladder capacity and bladder compliance increased to 303.9% and 189.9% of the preoperative level, and the maximum detrusor pressure decreased to 63.6% of the preoperative level. At 6-10 years after surgery, the maximum bladder capacity and bladder compliance increased to 490.2% and 627.9% and the maximum detrusor pressure decreased to 25.8% of the preoperative level. The UUTD of the patients was significantly reduced after surgery. The number of the high grade UUTD decreased to 116 (116/398, 29.2%) at 1-3 months and 51 (51/274, 18.6%) at 4-6 months. At 6-10 years, the number of the high-grade UUTD decreased to 4 (4/76, 5.3%) ( P<0.001), which was significantly lower than that before operation. The VUR was significantly relieved after operation, and 393 ureters had no VUR at 1-3 months, accounting for 97.8% (393/402) of the total ureters. Sustained remission of VUR was observed during follow-up. 73 ureters had no VUR at 6-10 years, accounting for 96.1% (73/76) of total ureters ( P<0.001). Patients' creatinine decreased to 79.0 (65.0-128.2) μmol/L at 1-3 months postoperatively, with a downward trend but no statistical difference, and creatinine levels were not significantly elevated at any postoperative time point compared with preoperative levels ( P>0.05). Postoperative complications included metabolic acidosis in 26 cases (9.9%), vesicoureteral anastomosis stenosis in 15 cases (5.7%), recurrent urinary tract infection in 16 cases (6.1%), and urinary calculi in 20 cases (7.6%), and intestinal obstruction requiring laparotomy in 8 cases (3.1%), all of them could be improved after treatments. Conclusions:AUEC is a safe and effective method for treating high-grade VUR or VUR with impaired anti-reflux mechanism, high-grade UUTD or UUTD with ureteral or vesicoureteral junction obstruction, and all of the complications can be improved after treatment. This technique can increase the bladder capacity and compliance, reconstruct the anti-reflux mechanism, and release upper urinary tract obstruction. It may play an important role in stabilizing and protecting the residual renal function from further deterioration.

Objective:To investigate the long term outcome of artificial urinary sphincter implantation for patients with stress urinary incontinence.Methods:The data of 46 patients who underwent artificial urethral sphincter implantation in China Rehabilitation Research Center from April 2002 to April 2022 were retrospectively analyzed.The patients’ age ranged from 19-80 years old (median 45.6 years). There were 45 males and 1 female. The history of illness was 8 months to 33 years. The patients category were urethral injuries associated urinary incontinence ( n=24), neurogenic urinary incontinence ( n=9) and post-prostatectomy incontinence ( n=13). Preoperative daily pad usage was 3.5±1.0. The impact of incontinence on the quality of life (QOL)measured by the visual analogue scale (VAS)was 7.1±1.2. All 46 patients underwent artificial urethral sphincter implantation, of which 20 patients were treated with anticholinergic drugs (5 cases) or urinary tract related surgery (urethral stenosis incision in 2 cases, sphincterectomy in 3 cases, urethral dilation in 5 cases, urethral calculus lithotripsy in 1 case, and augmentation cystoplasty in 4 cases) before artificial urethral sphincter implantation. Of the 45 male patients, 25 patients had the transperineal approach and 20 had the trans-scrotal approach. The female case had a trans-retropubic approach. Different cuffs size was used based on individual circumference of bulbar urethra (45 male cases: 4.5cm in 16 cases, 4.0cm in 29 cases; one female case: 8.0cm). Long-term surgical efficacy was evaluated. Assessments included postoperative urinary continence (socially continent: one pad per day or less; complete dry: wearing no pads), artificial urinary sphincter status and complications. The influences of patients of different etiologies, surgical approaches and cuff size on surgical results were compared. Results:The mean follow-up time was 7.1 years ranged from 6 months to 19 years. At the latest visit, 32 patients (69.6%) maintained the primary functional artificial urinary sphincter. Three patients (6.5%) had artificial urinary sphincter revisions and maintained continence with the new device. 11 patients (23.9%) removed the artificial urinary sphincter because of post-complications. Thirty-five patients were socially continent, of which 16 patients were totally dry, leading to the overall social continent rate as 76.1%(35/46). There was a significant reduction in pad usage to 1.2±0.6 diapers per day ( P<0.001). The impact of incontinence on the QOL measured by the VAS dropped to 2.6±1.9 ( P<0.001). The complication rate was 32.6%(15/46), including infections ( n=4), erosions ( n=5), mechanical failure ( n=3), dysurie ( n=2) and urethral atrophy ( n=1). There were no significant differences in social continent rate between patients with different etiologies[75.0%(18/24)vs. 66.7%(6/9) vs. 84.6%(11/13)], perioperative complications [37.5%(9/24)vs. 33.3%(3/9) vs. 23.1%(3/13)] and device re-intervention rate[37.5%(9/24) vs. 33.3%(3/9)vs. 15.4%(2/13)]. There were no statistically significant differences in postoperative complete dry rate [32%(8/25)vs. 40%(8/20), P=0.76] and postoperative device failure free rate [60%(15/25)vs. 80%(16/20), P=0.20] between trans-perineal group and trans-scrotal group. There was no statistically significant difference in postoperative social continent rate between 4.5cm cuff and 4.0 cuff[75%(12/16) vs. 65.5%(19/29), P=0.74]. Conclusions:Artificial urethral sphincter implantation is an effective treatment for stress urinary incontinence due to intrinsic sphincter deficiency. There was no difference in the continent rate and complication rate between patients of different etiologies, different surgical approaches and cuff size selection.

Objective: To develop a machine learning (ML) pipeline based on radiomics to predict Coronavirus Disease 2019 (COVID-19) severity and the future deterioration to critical illness using CT and clinical variables. Materials and Methods: Clinical data were collected from 981 patients from a multi-institutional international cohort with real-time polymerase chain reaction-confirmed COVID-19. Radiomics features were extracted from chest CT of the patients. The data of the cohort were randomly divided into training, validation, and test sets using a 7:1:2 ratio. A ML pipeline consisting of a model to predict severity and time-to-event model to predict progression to critical illness were trained on radiomics features and clinical variables. The receiver operating characteristic area under the curve (ROC-AUC), concordance index (C-index), and time-dependent ROC-AUC were calculated to determine model performance, which was compared with consensus CT severity scores obtained by visual interpretation by radiologists. Results: Among 981 patients with confirmed COVID-19, 274 patients developed critical illness. Radiomics features and clinical variables resulted in the best performance for the prediction of disease severity with a highest test ROC-AUC of 0.76 compared with 0.70 (0.76 vs. 0.70, p = 0.023) for visual CT severity score and clinical variables. The progression prediction model achieved a test C-index of 0.868 when it was based on the combination of CT radiomics and clinical variables compared with 0.767 when based on CT radiomics features alone (p < 0.001), 0.847 when based on clinical variables alone (p = 0.110), and 0.860 when based on the combination of visual CT severity scores and clinical variables (p = 0.549). Furthermore, the model based on the combination of CT radiomics and clinical variables achieved time-dependent ROC-AUCs of 0.897, 0.933, and 0.927 for the prediction of progression risks at 3, 5 and 7 days, respectively. Conclusion CT radiomics features combined with clinical variables were predictive of COVID-19 severity and progression to critical illness with fairly high accuracy.

Objective: To develop a machine learning (ML) pipeline based on radiomics to predict Coronavirus Disease 2019 (COVID-19) severity and the future deterioration to critical illness using CT and clinical variables. Materials and Methods: Clinical data were collected from 981 patients from a multi-institutional international cohort with real-time polymerase chain reaction-confirmed COVID-19. Radiomics features were extracted from chest CT of the patients. The data of the cohort were randomly divided into training, validation, and test sets using a 7:1:2 ratio. A ML pipeline consisting of a model to predict severity and time-to-event model to predict progression to critical illness were trained on radiomics features and clinical variables. The receiver operating characteristic area under the curve (ROC-AUC), concordance index (C-index), and time-dependent ROC-AUC were calculated to determine model performance, which was compared with consensus CT severity scores obtained by visual interpretation by radiologists. Results: Among 981 patients with confirmed COVID-19, 274 patients developed critical illness. Radiomics features and clinical variables resulted in the best performance for the prediction of disease severity with a highest test ROC-AUC of 0.76 compared with 0.70 (0.76 vs. 0.70, p = 0.023) for visual CT severity score and clinical variables. The progression prediction model achieved a test C-index of 0.868 when it was based on the combination of CT radiomics and clinical variables compared with 0.767 when based on CT radiomics features alone (p < 0.001), 0.847 when based on clinical variables alone (p = 0.110), and 0.860 when based on the combination of visual CT severity scores and clinical variables (p = 0.549). Furthermore, the model based on the combination of CT radiomics and clinical variables achieved time-dependent ROC-AUCs of 0.897, 0.933, and 0.927 for the prediction of progression risks at 3, 5 and 7 days, respectively. Conclusion CT radiomics features combined with clinical variables were predictive of COVID-19 severity and progression to critical illness with fairly high accuracy.

Objective To investigate the efficacy of CT scanning for 3D reconstruction and 3D printing in the internal fixation for in situ femoral condyle fractures.Methods A retrospective study was conducted of the 111 patients with in situ femoral condyle fracture who had been treated by internal fixation at Department of Traumatic Orthopaedics,The First People's Hospital of Hefei from June 2013 to January 2018.They were 59 males and 52 females,aged from 20 to 59 years(average,47 years).In 74 of them (observation group),the internal fixation was assisted by 3D printing using 3D images.There were 38 males and 36 females with an age of 44.5 ±4.7 years;there were 20 cases of type C1,40 cases of type C2 and 14 cases of type C3 according to the AO classification.In the other 37 patients (control group),the operation was assisted only by 3 D scanning.There were 21 males and 16 females with an age of 43.1 ±4.6 year;there were 8 cases of type C1,19 cases of type C2 and 10 cases of type C3 according to the AO classification.The 2 groups were compared in terms of operation time,clinical fracture healing time,intraoperative blood loss,hospital stay,number of fluoroscopy,knee joint score of Hospital for Special Surgery (HSS),fixation modes and postoperative complications.Results There were no significant differences in the preoperative general data between the 2 groups,showing comparability (P ＞ 0.05).All the patients were followed up for 8 to 12 months (average,10.6 months).The observation group had significantly shorter operation time (62.3 ± 4.7 minutes),fracture healing time (21.2 ± 3.4 weeks) and hospital stay (14.9 ± 3.3 days) than the control group (89.5 ± 6.0 minutes,25.1 ± 3.5 weeks,23.5 ± 3.5 days) (P ＜ 0.05).In the observation group,the intraoperative blood loss (84.1 ± 11.1 mL),fluoroscopy number (2.1 ±0.3 times) and HSS score (94.1 ± 4.2 points) were significantly less than those in the control group (129.6 ± 14.7 mL,4.7 ± 0.4 times and 86.5 ± 4.6 points) (P ＜ 0.05).There were no significant differences between the 2 groups in the use of L type iliac plate,dynamic iliac screws,retrograde interlocking intramedullary nail or minimally invasive internal fixation system (P ＞ 0.05).There were no significant differences in abnormal healing,joint adhesion,fixation fracture or incision infection between the 2 groups either (P ＞ 0.05).Conclusions CT scanning for 3D reconstruction can be used for multi-angle observation of the bone fragments in patients with femoral condyle fracture and 3D printing based on 3D reconstruction for manufacture of physical model of individualized fracture to assist the internal fixation.Combination of the two can help choose an appropriate fixation mode to facilitate fracture reduction.

Industrial biotechnology promises to make a significant contribution in enabling the sustainable development, and need the solid support from its basic discipline. As the basis of industrial biotechnology, industrial biology is to study the basic laws and mechanisms of biological behavior in industrial environment and to solve the key scientific problems for understanding, designing and constructing the organisms adapted to the application of industrial environment. In order to comprehend the status of industrial biology, we published this special issue to review the progress and trends of industrial biology from the three aspects of industrial protein science, cell science and fermentation science, respectively, for laying the foundation for the development of industrial biotechnology.
Biotechnology ; Fermentation ; Industrial Microbiology

The Alataw Pass, near the Ebinur Lake Wetland (northwest of China) and Taldykorgan (east of Kazakhstan), is a natural habitat for wild rodents. To date, little has been done on the surveillance of Bartonella spp. and Wolbachia spp. from fleas in the region. Here we molecularly detected Bartonella spp. and Wolbachia spp. in wild rodent fleas during January and October of 2016 along the Alataw Pass-Kazakhstan border. A total of 1,706 fleas belonging to 10 species were collected from 6 rodent species. Among the 10 flea species, 4 were found to be positive for Wolbachia, and 5 flea species were positive for Bartonella. Molecular analysis indicated that i) B. rochalimae was firstly identified in Xenopsylla gerbilli minax and X. conforms conforms, ii) B. grahamii was firstly identified in X. gerbilli minax, and iii) B. elizabethae was firstly detected in Coptopsylla lamellifer ardua, Paradoxopsyllus repandus, and Nosopsyllus laeviceps laeviceps. Additionally, 3 Wolbachia endosymbionts were firstly found in X. gerbilli minax, X. conforms conforms, P. repandus, and N. laeviceps laeviceps. BLASTn analysis indicated 3 Bartonella species showed genotypic variation. Phylogenetic analysis revealed 3 Wolbachia endosymbionts were clustered into the non-Siphonaptera Wolbachia group. These findings extend our knowledge of the geographical distribution and carriers of B. rochalimae, B. grahamii, B. elizabethae, and Wolbachia spp. In the future, there is a need for China-Kazakhstan cooperation to strengthen the surveillance of flea-borne pathogens in wildlife.
Bartonella ; Ecosystem ; Lakes ; Rodentia ; Siphonaptera ; Wetlands ; Wolbachia ; Xenopsylla