Characterization of gene regulatory networks underlying key properties in human hematopoietic stem cell ontogeny.

Human hematopoiesis starts at early yolk sac and undergoes site- and stage-specific changes over development. The intrinsic mechanism underlying property changes in hematopoiesis ontogeny remains poorly understood. Here, we analyzed single-cell transcriptome of human primary hematopoietic stem/progenitor cells (HSPCs) at different developmental stages, including yolk-sac (YS), AGM, fetal liver (FL), umbilical cord blood (UCB) and adult peripheral blood (PB) mobilized HSPCs. These stage-specific HSPCs display differential intrinsic properties, such as metabolism, self-renewal, differentiating potentialities etc. We then generated highly co-related gene regulatory network (GRNs) modules underlying the differential HSC key properties. Particularly, we identified GRNs and key regulators controlling lymphoid potentiality, self-renewal as well as aerobic respiration in human HSCs. Introducing selected regulators promotes key HSC functions in HSPCs derived from human pluripotent stem cells. Therefore, GRNs underlying key intrinsic properties of human HSCs provide a valuable guide to generate fully functional HSCs in vitro.

Large-scale generation of IL-12 secreting macrophages from human pluripotent stem cells for cancer therapy.

Genetically engineered macrophages (GEMs) have emerged as an appealing strategy to treat cancers, but they are largely impeded by the cell availability and technical challenges in gene transfer. Here, we develop an efficient approach to generate large-scale macrophages from human induced pluripotent stem cells (hiPSCs). Starting with 1 T150 dish of 106 hiPSCs, more than 109 mature macrophages (iMacs) could be generated within 1 month. The generated iMacs exhibit typical macrophage properties such as phagocytosis and polarization. We then generate hiPSCs integrated with an IL-12 expression cassette in the AAVS1 locus to produce iMacs secreting IL-12, a strong proimmunity cytokine. hiPSC-derived iMacs_IL-12 prevent cytotoxic T cell exhaustion and activate T cells to kill different cancer cells. Furthermore, iMacs_IL-12 display strong antitumor effects in a T cell-dependent manner in subcutaneously or systemically xenografted mice of human lung cancer. Therefore, we provide an off-the-shelf strategy to produce large-scale GEMs for cancer therapy.

Autophagy is essential for human myelopoiesis.

Emergency myelopoiesis (EM) is essential in immune defense against pathogens for rapid replenishing of mature myeloid cells. During the EM process, a rapid cell-cycle switch from the quiescent hematopoietic stem cells (HSCs) to highly proliferative myeloid progenitors (MPs) is critical. How the rapid proliferation of MPs during EM is regulated remains poorly understood. Here, we reveal that ATG7, a critical autophagy factor, is essential for the rapid proliferation of MPs during human myelopoiesis. Peripheral blood (PB)-mobilized hematopoietic stem/progenitor cells (HSPCs) with ATG7 knockdown or HSPCs derived from ATG7-/- human embryonic stem cells (hESCs) exhibit severe defect in proliferation during fate transition from HSPCs to MPs. Mechanistically, we show that ATG7 deficiency reduces p53 localization in lysosome for a potential autophagy-mediated degradation. Together, we reveal a previously unrecognized role of autophagy to regulate p53 for a rapid proliferation of MPs in human myelopoiesis.

Efficacy and Safety of Niraparib as First-Line Maintenance Treatment for Patients with Advanced Ovarian Cancer: Real-World Data from a Multicenter Study in China.

BACKGROUND: Poly (ADP-ribose) polymerase (PARP) inhibitors are a new maintenance therapy option for patients with ovarian cancer (OC). OBJECTIVE: To evaluate the efficacy and influencing factors of the novel PARP inhibitor niraparib for maintenance treatment of Chinese patients with advanced OC. PATIENTS AND METHODS: In this retrospective multicenter real-world study patients with advanced OC from 15 hospitals throughout China were enrolled. The primary endpoint was progression-free survival (PFS) and the secondary endpoints included the time to treatment discontinuation and safety. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to identify possible risk factors for PFS, after which a prediction model was established to evaluate the likelihood of achieving an 18-month PFS. The relationship between the dose of niraparib and PFS was also evaluated. RESULTS: The PFS rates of 199 patients at 6, 12, 18, 24, and 30 months were 87.4%, 75.9%, 63.6%, 56.1%, and 51.8%, respectively. LASSO regression model revealed that only age < 65 years (P = 0.011), BRCA mutations (P < 0.001), and R0 status after cytoreductive surgery (P = 0.01) were significant factors associated with prolonged PFS times. Based on the LASSO logistic regression analysis, a clinical prediction formula was developed: - 2.412 + 1.396Age≥65yr + 2.374BRCAwt + 1.387R1 + 0.793Interval≥12w + 0.178BMI>24kg/m2 which yielded a cut-off value of 0.091, an area under the curve (AUC) of 0.839 (0.763-0.916), a sensitivity of 94.3%, and an accuracy of 78.5%. A nomogram was then built to visualize the results. The major treatment-emergent adverse events of ≥ grade 3 included a platelet count decrease (19.1%), white blood cell count decrease (15.1%), neutrophil count decrease (13.1%), and anemia (18.6%). The 18-month PFS rates in patients treated with 200 mg niraparib were somewhat higher than in patients treated with 100 mg after 3-months of therapy. CONCLUSIONS: For Chinese OC patients, niraparib, particularly at a 200 mg individual starting dose, was an effective therapy with easily manageable safety.

Maintenance therapy with poly (ADP-ribose) polymerase inhibitors is a new option for patients with ovarian cancer (OC) after they have received platinum-based chemotherapy to reduce the recurrence or relapse rates, but it remains unclear whether there are any changes in efficacy and safety when different starting doses of niraparib are administrated to Chinese patients, who typically have a bodyweight < 77 kg. We found that niraparib exhibited satisfactory efficacy with tolerable safety during maintenance therapy for advanced OC whether administered at 100 mg or 200 mg doses. We believe these regimens can serve as a valuable addition to the previous results of randomized controlled trials.

Efficacy and safety of zimberelimab (GLS-010) monotherapy in patients with recurrent or metastatic cervical cancer: a multicenter, single-arm, phase II study.

OBJECTIVE: There is an unmet need to improve clinical outcomes for patients with recurrent/metastatic cervical cancer. Checkpoint inhibitors represent a promising treatment strategy. We evaluated the safety and anti-tumor activity of zimberelimab, an anti-programmed cell death protein-1 antibody, in patients with previously treated, recurrent, metastatic cervical cancer. METHODS: This phase II, single-arm, open-label study used a Simon two-stage minimax design. Eligible patients were women aged 18-75 years with programmed death ligand-1-positive recurrent or metastatic cervical cancer that had progressed after first- or subsequent-line chemotherapy (Eastern Cooperative Oncology Group (ECOG) performance status 0-1). Patients received intravenous zimberelimab (240 mg every 2 weeks) for 2 years until disease progression, intolerable adverse effects, or withdrawal from the study. The primary endpoint was objective response rate assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, by an independent review committee. RESULTS: A total of 105 patients were enrolled. Median age was 51 (range, 31-75) years; 63.8% had an ECOG performance status of 1. The median number of previous treatment lines was 1 (range, 1-4). Median follow-up was 16.9 (range, 16.3-18.4) months. The objective response rate was 27.6%, and the disease control rate was 55.2%. Median duration of response was not reached. Median overall survival was 16.8 months, and median progression-free survival was 3.7 months. The incidence of treatment-related adverse events of any grade was 78.1%, of which the most common were hypothyroidism (26.7%) and anemia (19.0%). CONCLUSION: Zimberelimab monotherapy demonstrated durable anti-tumor activity and an acceptable safety profile in patients with cervical cancer. CLINICAL TRIAL REGISTRATION: NCT03972722.

Generation of a humanized mesonephros in pigs from induced pluripotent stem cells via embryo complementation.

Heterologous organ transplantation is an effective way of replacing organ function but is limited by severe organ shortage. Although generating human organs in other large mammals through embryo complementation would be a groundbreaking solution, it faces many challenges, especially the poor integration of human cells into the recipient tissues. To produce human cells with superior intra-niche competitiveness, we combined optimized pluripotent stem cell culture conditions with the inducible overexpression of two pro-survival genes (MYCN and BCL2). The resulting cells had substantially enhanced viability in the xeno-environment of interspecies chimeric blastocyst and successfully formed organized human-pig chimeric middle-stage kidney (mesonephros) structures up to embryonic day 28 inside nephric-defective pig embryos lacking SIX1 and SALL1. Our findings demonstrate proof of principle of the possibility of generating a humanized primordial organ in organogenesis-disabled pigs, opening an exciting avenue for regenerative medicine and an artificial window for studying human kidney development.

Efficacy and Safety of Anlotinib in Overall and Disease-Specific Advanced Gynecological Cancer: A Real-World Study.

Purpose: Anlotinib is a novel oral small-molecule multi-target tyrosine kinase inhibitor that has been approved for treating non-small cell lung cancer. However, its efficacy and safety among patients with advanced gynecological cancer have not been comprehensively evaluated. We conducted this study to address this issue in the real-world setting. Patients and Methods: Data from patients treated with Anlotinib for persistent, recurrent or metastatic gynecological cancer were collected from 17 centers from August 2018. The database lock-time was on March 2022. Anlotinib was administered orally on days 1-14 every 3 weeks until disease progression, severe toxicity occurred, or death. In this study, disease-specific advanced gynecological cancer was mainly referred to cervical, endometrial, and ovarian cancer. The outcomes included objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Results: A total of 249 patients were analyzed, with a median follow-up of 14.5 months. The overall ORR and DCR were 28.1% [95% confidence interval (CI) 22.6% to 34.1%] and 80.7% (95% CI 75.3% to 85.4%), respectively. Specifically, the ORR varied from 19.7% to 34.4% and the DCR differed from 81.7% to 90.0% in disease-specific advanced gynecological cancer. The median PFS was 6.1 months and ranged from 5.6 to 10.0 months in the overall and disease-specific advanced gynecological cancer, respectively. Larger cumulative dosage of Anlotinib (>700 mg) was in general associated with longer PFS in the overall and disease-specific advanced gynecological cancer. The most common adverse event related to Anlotinib treatment was pain/arthralgia (18.3%). Conclusion: In conclusion, Anlotinib holds promise in treating patients with advanced gynecological cancer including its disease-specific types, with reasonable efficacy and tolerable safety.

Value analysis of next-generation sequencing combined with Xpert in early precise diagnosis of pulmonary tuberculosis.

The current study aims to investigate the value of combination of NGS with Xpert MTB/RIF in the diagnosis of early pulmonary tuberculosis (PTB). A total of 85 patients with suspected PTB were analyzed retrospectively. The positive detection rates of PTB by Xpert MTB/RIF, TBseq Ultra, TB-DNA, and TB-RNA were significantly higher than those by acid-fast staining. Xpert MTB/RIF, TBseq Ultra, TB-DNA, and TB-RNA possessed higher sensitivity and accuracy than acid-fast stained smears. Kappa agreement analysis showed good agreement between Xpert MTB/RIF and TBseq Ultra. Combined diagnosis improves the detection sensitivity compared with a single diagnostic method. ROC curve analysis showed that Xpert MTB/RIF combined with TBseq Ultra showed the highest area under the curve (0.886). In conclusion, the combined diagnosis of TBseq Ultra and Xpert MTB/RIF harbors the characteristics of short cycle, high specificity and accuracy, which demonstrated a promising application value in the early diagnosis of PTB.

Circulating HDAC4 reflects lipid profile, coronary stenosis and inflammation in coronary heart disease patients.

Aim: To investigate the clinical value of HDAC4 in coronary heart disease (CHD) patients. Methods: The serum HDAC4 levels were determined by ELISA in 180 CHD patients and 50 healthy controls. Results: HDAC4 was decreased in CHD patients compared with healthy controls (p < 0.001). HDAC4 was negatively linked with serum creatinine (p = 0.014), low-density lipoprotein cholesterol (p = 0.027) and C-reactive protein (p = 0.006) in CHD patients. Moreover, HDAC4 was inversely related to TNF-α (p = 0.012), IL-1ß (p = 0.002), IL-6 (p = 0.034), IL-17A (p = 0.023), VCAM1 (p = 0.014) and Gensini score (p = 0.001). Unfortunately, neither HDAC4 high (vs low) (p = 0.080) nor HDAC4 quartile (p = 0.268) estimated major adverse cardiovascular event risk. Conclusion: Circulating HDAC4 levels have disease monitoring value but are less valuable in estimating prognosis in CHD patients.

What was this article about? This study aimed to assess the clinical significance of identifying a marker named histone deacetylase 4 (HDAC4) in coronary heart disease (CHD) patients. What was done? Blood was taken from 180 CHD patients and 50 healthy controls, and their blood HDAC4 levels were evaluated. What were the results? HDAC4 levels were higher in CHD patients than in the controls. The CHD patients with a higher HDAC4 level had good kidney health and lower lipid profile, milder inflammation, good vascular status and less narrowing in their blood vessels. However, the HDAC4 level was not found to predict the risk of future cardiovascular disease. What do the results mean? A higher HDAC4 level in the blood of CHD patients suggests a better symptomatic disease status.

The efficiency of quick response code versus telephone contact for post-discharge follow-up after ophthalmic day surgery: a randomized controlled trial.

PURPOSE: To assess and compare the efficiency of quick response (QR) code versus telephone contact for post-discharge follow-up in patients receiving low-risk ophthalmic day surgery. METHODS: One hundred and sixty patients undergoing strabismus day-care surgery with general anesthesia were randomly allocated to either the intervention group using QR code (QR group) or the control group receiving telephone call (TEL group) for post-discharge follow-up. The primary outcome was the follow-up overall attendance rate on the second postoperative day. Secondary outcomes included attendance rate at the first scheduled follow-up, number of text message reminders, elapsed time and estimated cost for follow-up, omission rate of follow-up responses, and patient satisfaction. RESULTS: The overall attendance rate of follow-up was significantly higher in the QR group than that in the TEL group (97.5% vs. 87.5%, p = 0.016). As compared with the TEL group, the QR group significantly reduced the number of text message reminders with higher attendances at the first scheduled follow-up (p < 0.001, p = 0.001). Besides, the TEL group cost a median time of 258 s and a median cost of RMB 5.8 yuan to complete a follow-up consultant, but was associated with a significantly high omission rate of follow-up responses comparing to the QR group (p = 0.002). Patient satisfaction was comparable between two groups. CONCLUSION: QR code follow-up can be more efficient than traditional telephone contact in assessing the post-discharge recovery after strabismus day surgery, which provides a safe and intuitively alternative follow-up pathway for identifying issues that may necessitate further clinical care for more low-risk ophthalmic day surgeries.

Effect of Multimodal Preemptive Analgesia of Flurbiprofen Axetil, Nalbuphine, and Retrobulbar Block on Postoperative Pain and Enhanced Recovery in Patients Undergoing Oculoplastic Day Surgery: A Prospective, Randomized, Double-Blinded Study.

PURPOSE: To evaluate the effect of either flurbiprofen axetil or nalbuphine combined with retrobulbar block (RB) before surgery on postoperative pain control and enhanced recovery in day-care patients undergoing orbital implantation. METHODS: A total of 45 patients undergoing orbital implantation with general anesthesia were randomly divided into three groups: flurbiprofen axetil (1 mg/kg) combined with RB (group F), nalbuphine (0.1 mg/kg) combined with RB (group N), and placebo as normal saline with RB (group C). The primary outcome was the average pain score (numeric rating scale: 0-10) within the first 24 hours. Other outcomes including the peak pain score, paracetamol requirement, quality of recovery (QoR)-15, and adverse effects (AEs) were assessed. RESULTS: The average and peak pain scores within 24 hours after surgery in group F were significantly lower than in other groups ( p < 0.0167). Compared with group C, the NRS scores were significantly decreased at 2 and 4 hours in group F, and 2 hours in group N after surgery ( p < 0.0167), but without significant differences at other measured time points. The time to first paracetamol oral intake displayed a significant difference among the three groups ( p < 0.0167). CONCLUSION: Preemptive use of flurbiprofen axetil 1 mg/kg combined with RB is an optimal choice for multimodal analgesia for day-care patients undergoing orbital implantation in terms of efficient acute pain control, without impeding patient-enhanced recovery.

Model estimation and selection for partial linear varying coefficient EV models with longitudinal data.

In this paper, we consider the estimation and model selection for longitudinal partial linear varying coefficient errors-in-variables (EV) models when the covariates are measured with some additive errors. Bias-corrected penalized quadratic inference functions method is proposed based on quadratic inference functions with two penalty function terms. The proposed method can not only handle the measurement errors of covariates and within-subject correlations but also estimate and select significant non-zero parametric and nonparametric components simultaneously. With some regularization conditions, the resulting estimators of parameters are asymptotically normal and the estimators of nonparametric varying coefficient achieves the optimal convergence rate. Furthermore, we present simulation studies and a real example analysis to evaluate the finite sample performance of the proposed method.

Predicted lean body mass, fat mass, and heart failure in patients with type 2 diabetes mellitus.

BACKGROUND: High body mass index (BMI) is associated with a higher risk of heart failure (HF) in patients with new-onset type 2 diabetes mellitus (T2DM). However, limited studies have investigated the independent association between fat mass or lean body mass and HF risk among T2DM patients with cardiovascular disease (CVD) or high CVD risk. OBJECTIVES: To investigate the association between fat mass index (FMI, kg/m2) or lean BMI (LBMI, kg/m2) and HF risk. METHODS: This was a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. Cox proportional-hazards models were applied to evaluate the association of FMI, LBMI, and BMI with HF risk. Discordant analysis was performed to compare the magnitude of this associations. RESULTS: HF occurred in 356 participants (3.7%). After adjusting for confounding factors, higher FMI values were independently associated with HF risk (HR: 1.72, 95% CI: 1.15-2.57, each 1 SD increase in FMI); LBMI was a protective risk factor for HF (HR: 0.58, 95% CI: 0.38-0.87,). After further adjusting for FMI, the association between BMI and HF risk (HR, 0.97; 95% CI, 0.67-1.42) disappeared. Compared with concordant values below the medians, discordant FMI above the median with BMI below yielded an HR of 1.78 (95% CI: 1.14-2.78) for HF. In contrast, BMI above the median with FMI below was not associated with HF risk (HR: 1.09, 95% CI: 0.57-2.09). CONCLUSIONS: The risk of HF conferred by higher BMI was primarily driven by the association between FMI and HF. After adjusting for BMI, LBMI played a protective role.

Serum brain-derived neurotrophic factor in coronary heart disease: Correlation with the T helper (Th)1/Th2 ratio, Th17/regulatory T (Treg) ratio, and major adverse cardiovascular events.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) exerts protective roles against dyslipidemia, atherosclerosis, and inflammation in cardiovascular diseases; meanwhile, it retards CD4+ T cell differentiation into T helper (Th)1 and Th17 cells. Hence, this study aimed to investigate the linkage of serum BDNF with Th1/Th2 ratio, Th17/regulatory T (Treg) ratio, and major adverse cardiovascular events (MACE) risk in the coronary heart disease (CHD) patients. METHODS: This prospective study detected serum BDNF in 210 CHD patients, 50 disease controls (DCs), and 50 healthy controls (HCs) using an enzyme-linked immunosorbent assay. For CHD patients only, the proportion of Th1, Th2, Th17, and Treg cells in blood CD4+ T cells was calculated by flow cytometry. RESULTS: The BDNF varied among CHD patients, DC, and HC (p < 0.001). Specifically, BDNF was declined in CHD patients compared with DCs (p < 0.001) and HCs (p < 0.001). In CHD patients, BDNF was negatively related to Th1 cells (p = 0.031), Th1/Th2 ratio (p = 0.026), Th17 cells (p = 0.001), and Th17/Treg ratio (p = 0.002). Concerning the prognosis, BDNF was reduced in patients with MACE occurrence compared to patients without MACE occurrence (p = 0.006). Furthermore, BDNF showed a trend (lacked statistical significance) to relate to longer MACE-free survival (p = 0.059). Besides, BDNF was related to the absence of obesity (p = 0.019), decreased total cholesterol (p = 0.043), low-density lipoprotein cholesterol (p = 0.019), C-reactive protein (p = 0.012), and Gensini score (p = 0.005). CONCLUSION: Serum BDNF negatively correlates with Th1/Th2 ratio, Th17/Treg ratio, and estimates lower MACE risk in CHD patients.

MiR-342-5p protects neurons from cerebral ischemia induced-apoptosis through regulation of Akt/NF-κB pathways by targeting CCAR2.

OBJECTIVES: Ischemic stroke causes high morbidity, mortality and health burden in the world. MiR-342-5p was associated with Alzheimer's disease and cardio-protection. Herein, we aimed to reveal effects of miR-342-5p on cerebral ischemia injury as well as novel targets for stroke. MATERIALS AND METHODS: AgomiR-342-5p was intracerebroventricularly injected into the middle cerebral artery occlusion (MCAO) mouse models to evaluate functions of miR-342-5p on cerebral ischemia. RT-qPCR and western blot assays were used to evaluate genes expression. Oxygen-glucose deprivation (OGD) was used as an in vitro model for ischemia. Viability and apoptosis ratio of neurons was evaluated by CCK-8, LDH release detection, and flow cytometry. The potential targets of miR-342-5p were predicted by Targetscan, and their interaction was confirmed by luciferase assay. RESULTS: The intervention of miR-342-5p effectively attenuated ischemic injury in MCAO mice. MiR-342-5p overexpression could protect neurons against OGD-induced injury, as revealed by increased cell viability and BCL2 expression, and decreased LDH release, apoptosis ratio, and BAX expression in OGD-induced neurons. Mechanically, miR-342-5p could directly bound with CCAR2 to inhibit its expression. Overexpressing CARR2 aggravated the OGD-induced injury of neurons, which was partly restrained by overexpressing miR-342-5p reversed. Furthermore, miR-342-5p/CARR2 axis regulates Akt/NF-κB signaling pathway in vitro as well as in vivo cerebral ischemia models. CONCLUSIONS: MiR-342-5p inhibited neuron apoptosis by regulating Akt/NF-kB signaling pathway via CCAR2 suppression. Our findings revealed the neuroprotection of miR-342-5p in cerebral ischemia.

Clinical value of long non-coding RNA KCNQ1OT1 in estimating the stenosis, lipid level, inflammation status, and prognostication in coronary heart disease patients.

OBJECTIVE: Long non-coding RNA KQT-like subfamily, member 1 opposite strand/antisense transcript 1 (KCNQ1OT1) could regulate lipid metabolism, vascular smooth muscle cell function, inflammation, and atherosclerosis. This study aimed to evaluate whether lncRNA KCNQ1OT1 could serve as a biomarker for reflecting coronary heart disease (CHD) patients' disease situation and prognosis. METHODS: LncRNA KCNQ1OT1 expression was determined in peripheral blood mononuclear cells from 267 CHD patients, 50 disease controls (DCs) (unexplained chest pain), and 50 healthy controls (HCs) by the RT-qPCR method. TNF-α, IL-17A, VCAM-1, and ICAM-1 were determined by the ELISA procedure in serum from CHD patients only. The mean (95% confidential interval) follow-up duration was 16.0 (15.3-16.8) months. RESULTS: LncRNA KCNQ1OT1 was highest in CHD patients, followed by DCs, and lowest in HCs (p < 0.001). LncRNA KCNQ1OT1 could distinguish the CHD patients from DCs (area under the curve [AUC]: 0.757) and from the HCs (AUC: 0.880). LncRNA KCNQ1OT1 was positively associated with triglyceride (p = 0.026), low-density lipoprotein cholesterol (p = 0.023), cardiac troponin I (p = 0.023), and C-reactive protein (p = 0.001). Besides, lncRNA KCNQ1OT1 was also positively linked with the Gensini score (p = 0.008). Furthermore, lncRNA KCNQ1OT1 was positively related to the TNF-α (p < 0.001), IL-17A (p = 0.008), and VCAM-1 (p = 0.003). LncRNA KCNQ1OT1 was elevated in CHD patients with MACE compared to those without MACE (p = 0.006); moreover, lncRNA KCNQ1OT1 high was associated with shorter MACE-free survival (p = 0.018). CONCLUSION: Circulating lncRNA KCNQ1OT1 expression not only reflects the stenosis degree, blood lipid level, and inflammation status but also predicts the MACE risk, while a large-scale study is needed for verification.

Generation of a homozygous FIS1 knockout human embryonic stem cell line GIBHe015-B by CRISPR/Cas9 system.

The mitochondrial fission protein 1 (FIS1) is essential for mitochondrial division or fission and has been determined to mediate mitochondrial and peroxisomal fission. Other studies also found that FIS1 functions as an essential component of the mitophagy and apoptosis pathways in mammalian cells, suggesting that FIS1 has multiple important roles. Here, we generated homozygous FIS1 knockout human embryonic stem cells (hESCs) using the CRISPR/Cas9 system. This cell line exhibits normal karyotype, pluripotency, and trilineage differentiation potential, which could provide a useful cellular resource for exploring the functions of FIS1 and their implications in human health and diseases.

Diagnostic value of ultrasound-guided transbronchial lung biopsy in peripheral tuberculous pulmonary lesions.

BACKGROUND: To investigate the diagnostic value of bronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB) in tuberculous peripheral pulmonary lesions. METHODS: A total of 770 patients who completed CT imaging and ultrasound bronchoscopy were retrospectively analyzed. All patients underwent biopsy sampling as well as alveolar lavage under the guidance of ultrasound. Pathological analysis and molecular biological detection of pulmonary tuberculosis were performed in both pathological tissues and bronchoalveolar lavage fluid (BALF), and the diagnostic positive rate and diagnostic sensitivity were statistically analyzed. RESULTS: Of the 44 patients who were found to have lesions by EBUS-TBLB, 26 patients were able to achieve a definite diagnosis of PPLs, with an overall diagnostic yield of 59.1%. Of the 33 patients with all diagnosed benign lesions, 22 were diagnosed with active pulmonary tuberculosis with the diagnostic yield of 66.7%. Among above 22 cases, the overall positive rate of BALF diagnosis was as high as 95.6%, and the highest diagnostic rate of a single test was BALF XpertMTB/RIF, 59.1%. Compared with pathological tissues, the diagnostic positive rate of BALF as a diagnostic specimen was higher (p < .05). In addition, the diagnostic yield of EBUS-TBLB in pulmonary tuberculosis was not affected by patient's age, lesion extent size, EBUS probe position, presence or tracheal grade, or characteristics of lesions (all p > .05). CONCLUSION: Transbronchial radial ultrasound-guided lung biopsy of tuberculous PPLs possesses higher diagnostic rate, fewer complications and less interference, exerts potential application value in the diagnosis of tuberculous peripheral pulmonary lesions.

Quality improvement of shrimp (Litopenaeus vannamei) during refrigerated storage by application of Maillard peptides/water-soluble chitosan coating.

We investigated the effect of squid Maillard peptides (SMPs) on the shelf life and quality of shrimp for 20 days. Water-soluble chitosan coatings incorporated with SMPs (SMPs + chitosan) were applied to shrimp under chilled conditions. Untreated samples were used as control, along with samples treated with water-soluble chitosan and SMPs alone. The pH increase was observed in all samples, as well as increased total plate count, total volatile basic nitrogen, peroxide value, and thiobarbituric acid index. However, these indexes in the SMPs + chitosan group were lower than the other three groups, which suggested SMPs + chitosan might play a role in retarding quality loss of shrimp, and there might be a combined effect between water-soluble chitosan and SMPs. Based on hardness, springiness, and sensory evaluation, shrimp coated with SMPs + chitosan was the best preserved, with a shelf life of 16 days but only 8-12 days for other samples. The present work demonstrates the effectiveness of SMPs + chitosan, offering a promising alternative to inhibit microbial growth and lipid oxidation on shrimps during refrigerated storage.

A Novel Multitasking Ant Colony Optimization Method for Detecting Multiorder SNP Interactions.

MOTIVATION: Linear or nonlinear interactions of multiple single-nucleotide polymorphisms (SNPs) play an important role in understanding the genetic basis of complex human diseases. However, combinatorial analytics in high-dimensional space makes it extremely challenging to detect multiorder SNP interactions. Most classic approaches can only perform one task (for detecting k-order SNP interactions) in each run. Since prior knowledge of a complex disease is usually not available, it is difficult to determine the value of k for detecting k-order SNP interactions. METHODS: A novel multitasking ant colony optimization algorithm (named MTACO-DMSI) is proposed to detect multiorder SNP interactions, and it is divided into two stages: searching and testing. In the searching stage, multiple multiorder SNP interaction detection tasks (from 2nd-order to kth-order) are executed in parallel, and two subpopulations that separately adopt the Bayesian network-based K2-score and Jensen-Shannon divergence (JS-score) as evaluation criteria are generated for each task to improve the global search capability and the discrimination ability for various disease models. In the testing stage, the G test statistical test is adopted to further verify the authenticity of candidate solutions to reduce the error rate. RESULT: Three multiorder simulated disease models with different interaction effects and three real age-related macular degeneration (AMD), rheumatoid arthritis (RA) and type 1 diabetes (T1D) datasets were used to investigate the performance of the proposed MTACO-DMSI. The experimental results show that the MTACO-DMSI has a faster search speed and higher discriminatory power for diverse simulation disease models than traditional single-task algorithms. The results on real AMD data and RA and T1D datasets indicate that MTACO-DMSI has the ability to detect multiorder SNP interactions at a genome-wide scale. Availability and implementation: https://github.com/shouhengtuo/MTACO-DMSI/.