The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

OBJECTIVES: To investigate the role of the BNIP3-PI3K/Akt signaling pathway in mediating the inhibitory effect of Buyang Huanwu Decoction (BYHWT) on mitochondrial autophagy in human synovial fibroblasts from rheumatoid arthritis patients (FLS-RA) cultured under a hypoxic condition. METHODS: Forty normal Wistar rats were randomized into two groups (n=20) for daily gavage of BYHWT or distilled water for 7 days to prepare BYHWT-medicated or control sera. FLS-RA were cultured in routine condition or exposed to hypoxia (10% O₂) for 24 h wigh subsequent treatment with IL-1β, followed by treatment with diluted BYHWT-medicated serum (5%, 10% and 20%) or control serum. AnnexinV-APC/7-AAD double staining and T-AOC kit were used for detecting apoptosis and total antioxidant capacity of the cells, and the changes in ROS, ATP level, mitochondrial membrane potential and Ca²⁺ homeostasis were analyzed. The changes in mRNA and protein expressions of BNIP3, PI3K and AKT and mRNA expressions of LC3, Beclin-1 and P62 were detected using RT-qPCR and Western blotting. RESULTS: Treatment with BYHWT-medicated serum dose-dependently lowered apoptosis rate of IL-1β-induced FLS-RA with hypoxic exposure. The treatment significantly decreased T-AOC concentration, increased ROS production, autophagosome formation and ATPase levels, and lowered mitochondrial membrane potential and Ca²⁺ level in the cells. In IL-1β-induced FLS-RA with hypoxic exposure, treatment with BYHWT-medicated serum significantly increased BNIP3 protein expression, decreased the protein expressions of PI3K and AKT, increased the mRNA expressions of BNIP3 and P62, and lowered the mRNA expressions of PI3K, AKT, LC3 and Beclin-1 without significantly affecting Beclin-1 protein expression. The cells treated with 5% and 10% BYHWT-medicated serum showed no significant changes in LC3 expression. CONCLUSIONS BYHWT inhibits mitochondrial autophagy in IL-1β-induced FLS-RA with hypoxic exposure possibly by inhibiting BNIP3-mediated PI3K/AKT signaling pathway.
Drugs, Chinese Herbal/pharmacology* ; Arthritis, Rheumatoid/pathology* ; Animals ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Autophagy/drug effects* ; Humans ; Fibroblasts/cytology* ; Rats, Wistar ; Membrane Proteins/metabolism* ; Rats ; Phosphatidylinositol 3-Kinases/metabolism* ; Mitochondria/metabolism* ; Cells, Cultured ; Proto-Oncogene Proteins/metabolism* ; Apoptosis/drug effects* ; Cell Hypoxia ; Synovial Membrane/cytology* ; Male ; Mitochondrial Proteins

In China, the crude oil supply is highly dependent on overseas countries, and thus strengthening crude oil self-sufficiency has become an important issue of the national energy security. Tertiary oil recovery, especially polymer flooding, has been widely applied in large oil fields in China, which can increase the recovery rate by 15%-20% compared with water flooding. However, the widely used oil flooding polymers show poor thermal stability and salinity tolerance, complicated synthesis ways of monomers, and environmental unfriendliness. Moreover, the polymer flooding induces problems including pore plugging, heterogeneity intensification, high dispersion of remaining oil resources, pressure rise in injection wells, and low efficiency circulation of injection medium, which restrict the subsequent recovery of old oil fields. Here, we systematically review the developing and current situations of polymer flooding, introduce the innovative biomanufacturing of oil flooding polymers and their monomers or precursors as well as low-cost bio-based chemical raw materials for multiple compound flooding. The comprehensive study of the relationships between microbial fermentation metabolites and polymer flooding will reveal the green and low-carbon paths for polymer flooding. Such study will enable the application of enzymes produced by microorganisms in polymer production and polymer plugging removal after polymer flooding as well as the application of microbial metabolites such as biosurfactants, organic acids, alcohols, biogas, and amino acids in enhancing oil recovery. This review suggests that incorporating biomanufacturing into polymer flooding will ensure the high productivity and stability for crude oil production in China.
Polymers/metabolism* ; China ; Petroleum ; Oil and Gas Fields

O-acetyl-L-homoserine (OAH) is a promising platform compound for the production of L-methionine and other valuable compounds, while its low yield and low conversion rate limit the industrial application. To solve these problems, we constructed a strain for high OAH production with the previously constructed L-homoserine producer Escherichia coli HS33 as the chassis by systematic metabolic engineering. Firstly, PEP accumulation, pyruvate utilization, and OAH synthesis pathway (overexpressing aspB, aspA, and thrA^C1034T) were enhanced to obtain an initial strain accumulating 13.37 g/L OAH. Subsequently, the co-factor synthesis genes were integrated to supply reducing power and energy, which increased the yield to 15.79 g/L. The OAH yield of the engineered strain OAH28 was further increased to 17.49 g/L by strengthening the acetic acid reuse pathway, improving the supply of acetyl-CoA, and regulating the expression of MetX from different sources. Finally, in a 5 L fermenter, OAH28 achieved an OAH titer of 47.12 g/L, with a glucose conversion rate of 32% and productivity of 0.59 g/(L·h). The results lay a foundation for increasing the OAH production by metabolic engineering and give insights into the industrial production of OAH.
Metabolic Engineering/methods* ; Escherichia coli/genetics* ; Homoserine/biosynthesis* ; Fermentation

Synthetic biology is a crucial tool for the development of the bio-industry and bio-economy, representing a significant aspect of new quality productive forces. As a core course for graduate students in bioengineering, Synthetic Biology plays a vital role in ensuring the supply of essential talents for the development of the bio-industry in the new era. To better serve regional economic development and provide high-level talents for China's progress in the bio-industry, we analyzed typical issues encountered in the past teaching activities, set up a multi-disciplinary teaching team, optimized the course contents, adjusted the teaching mode, and mobilized students' learning interest. With the application of scientific research project as the starting point, we guided students to think and discuss deeply through the simulation of application writing and project defense, which improved students' critical thinking and innovative thinking. With industrialization as a focus, we explored a new training model combining production, education, and research through the joint practice base of the university and enterprises introduced typical cases of biomanufacturing to encourage students to engage in scientific research. The teaching reform significantly enhances the comprehensive abilities and national sentiments of graduate students. This paper hopes to serve as a reference for colleagues engaged in teaching in this field.
Synthetic Biology/education* ; Teaching ; China ; Humans

Objective To investigate the serum levels of semaphorin 3E(Sema3E)in patients with intracranial aneurysms,revealing the correlation between Sema3E and 1-month poor prognosis after interventional embolization.Methods This study was a prospective single-center cohort study,recruiting 102 consecutive patients with intracranial aneurysms who underwent interventional surgery from June 2020 to January 2022 in our hospital.Among them,11 patients were excluded.Clinical and radiological profiles were collected.Peripheral blood was collected after admission,and serum Sema3E levels were determined by enzyme-linked immunosorbent assay.All the aneurysms were treated with endovascular coil embolization or stent-assisted coil embolization.The primary outcome was evaluated with the Glasgow Outcome Scale(GOS)1 month after interventional therapy.The favorable outcome was defined as a GOS score of 4-5,and a poor outcome was defined as a GOS score of 1-3(severe disability,vegetative state,or death).Univariate and multivariate logistic regression analyses were used to identify potential prognostic factors after interventional therapy.Results The average age of 91 patients with intracranial aneurysm was 59.9±11.0 years old,including 70 cases(76.9%)with favorable prognosis and 21 cases(23.1%)with poor prognosis.The mean preoperative Glasgow Coma Scale(GCS)score of the poor prognosis group(9.4±4.5)was significantly lower than that of the favorable prognosis group(13.3±2.5;P<0.001).In the poor prognosis group,the Hunt-Hess grade(3.6±0.6 vs.2.0±1.3,P<0.001)and the serum Sema3E levels[(6.21±1.58)μg/L vs.(4.38±1.77)μg/L,P<0.001]were significantly higher than those in the favorable prognosis group.Logistic regression analysis showed the Hunt-Hess grade(OR =7.150,P =0.003),stent-assisted coil embolization(OR =15.777,P =0.010),and the serum Sema3E level(OR =1.756,P =0.027)were independent prognostic factors for intracranial aneurysms after interventional therapy.Conclusions The serum Sema3E level is closely correlated with the severity of intracranial aneurysms.The serum Sema3E level is a prognostic factor for interventional treatment,which can be used as a biomarker for predicting poor outcomes.

A 72-year-old male patient with right lung squamous cell carcinoma treated with 1 cycle of pembrolizumab combination chemotherapy and pembrolizumab 200 mg monotherapy.After 20 days of treatment,a small amount of erythema appeared around the mouth,head,neck,chest and back,accompanied by itching.Then the lesions aggravated progressively,spreading to the head,limbs,buttocks and perianal area,with blisters and epidermal detachment and necrosis,and the lesions involved＞70％of the body surface area,and the pain was obvious.After multidisciplinary consultation,toxic epidermal necrolysis(TEN)was considered.The patient's lesions gradually improved and regressed after treatment with hormones,adjunctive therapy with intravenous immunoglobulin,wound care,infection prevention and nutritional support.TEN adverse reactions were highly likely to be associated with pembrolizumab.This paper reviewed the literature on the cases of TEN induced by pembrolizumab.It analyzed the clinical characteristics and drug treatment strategies of TEN induced by pembrolizumab,to improve clinical staff's ability to recognize and manage immunosuppressant-related skin toxicity and improve the prognosis of tumor patients.

Although the development of COVID-19 vaccines has been a remarkable success, the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict. In this study, blood samples were collected from 163 participants who next received two doses of an inactivated COVID-19 vaccine (CoronaVac®) at a 28-day interval. Using TMT-based proteomics, we identified 1,715 serum and 7,342 peripheral blood mononuclear cells (PBMCs) proteins. We proposed two sets of potential biomarkers (seven from serum, five from PBMCs) at baseline using machine learning, and predicted the individual seropositivity 57 days after vaccination (AUC = 0.87). Based on the four PBMC's potential biomarkers, we predicted the antibody persistence until 180 days after vaccination (AUC = 0.79). Our data highlighted characteristic hematological host responses, including altered lymphocyte migration regulation, neutrophil degranulation, and humoral immune response. This study proposed potential blood-derived protein biomarkers before vaccination for predicting heterogeneous antibody generation and decline after COVID-19 vaccination, shedding light on immunization mechanisms and individual booster shot planning.
Humans ; COVID-19 Vaccines ; Leukocytes, Mononuclear ; Proteomics ; COVID-19/prevention & control* ; Vaccination ; Antibodies ; Antibodies, Viral ; Antibodies, Neutralizing

There are gradual increases in the incidence rates of metabolic associated fatty liver disease （MAFLD） and type 2 diabetes mellitus （T2DM）， with close relationship and mutual interaction between the two diseases， but the specific mechanism is still unclear. Studies have shown that T2DM and MAFLD may cause aggravation of each other through insulin resistance， inflammation， some hepatocyte factors， and cellular senescence and protect each other through some hepatocyte factors. Further research on the association between T2DM and MAFLD and the mechanism of comorbidity is of great significance for the clinical prevention and treatment of the two diseases.

Pheochromocytoma and paranganglioma (PPGL) is a rare neuroendocrine tumor. In recent years, the continuous development of multimodal imaging, pathonomics, genomics, transcriptomics, epigenomics, metabolism and proteomics have provided us with ideas to better understand the complex transfer mechanism of PPGL. This paper will review the precise typing system of PPGL, current research advances in the diagnosis and clinical prognosis.