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The Sc(iii)-catalyzed [2,3]-sigmatropic rearrangement of sulfonium ylides derived from azoalkenes has been established, which represents the first non-carbenoid variant of the Doyle–Kirmse reaction.

Idiopathic pulmonary fibrosis (IPF) is a fibrotic interstitial lung disease in which collagen progressively deposits in the supporting framework of the lungs. The pathological collagen creates a recalcitrant barrier in mesenchyme for drug penetration, thus greatly restricting the therapeutical efficacy. On the other hand, this overloaded collagen is gradually exposed to the bloodstream at fibrotic sites because of the vascular hyperpermeability, thus serving as a potential target. Herein, pathological collagen targeting and penetrating liposomes (DP-CC) were constructed to deliver anti-fibrotic dual drugs including pirfenidone (PFD) and dexamethasone (DEX) deep into injured alveoli. The liposomes were co-decorated with collagen binding peptide (CBP) and collagenase (COL). CBP could help vehicle recognize the pathological collagen and target the fibrotic lungs efficiently because of its high affinity to collagen, and COL assisted in breaking through the collagen barrier and delivering vehicle to the center of injured sites. Then, the released dual drugs developed a synergistic anti-fibrotic effect to repair the damaged epithelium and remodel the extracellular matrix (ECM), thus rebuilding the lung architecture. This study provides a promising strategy to deliver drugs deep into pathological collagen accumulated sites for the enhanced treatment of IPF.

Upper gastrointestinal endoscopy is critical for esophageal squamous cell carcinoma (ESCC) detection; however, endoscopists require long-term training to avoid missing superficial lesions.To develop a deep learning computer-assisted diagnosis (CAD) system for endoscopic detection of superficial ESCC and investigate its application value.We configured the CAD system for white-light and narrow-band imaging modes based on the YOLO v5 algorithm. A total of 4447 images from 837 patients and 1695 images from 323 patients were included in the training and testing datasets, respectively. Two experts and two non-expert endoscopists reviewed the testing dataset independently and with computer assistance. The diagnostic performance was evaluated in terms of the area under the receiver operating characteristic curve, accuracy, sensitivity, and specificity.The area under the receiver operating characteristics curve, accuracy, sensitivity, and specificity of the CAD system were 0.982 [95% confidence interval (CI): 0.969-0.994], 92.9% (95%CI: 89.5%-95.2%), 91.9% (95%CI: 87.4%-94.9%), and 94.7% (95%CI: 89.0%-97.6%), respectively. The accuracy of CAD was significantly higher than that of non-expert endoscopists (78.3%,The diagnostic performance of the CAD system is promising and may assist in improving detectability, particularly for inexperienced endoscopists.

Li Fang,1,2 Chun-Hao Li,1,3 Qian Zhang,1,3 Tian-Jiao Jiang,1,3 Yuan Liu,1,2 Feng-Po Shi,1,3 Peng Yu,1,3 Liang Yu,1,3 Ai-Ping Chen,1,3 Tao Li,1,3 Yu-Zhu Wan,1,3 Li Shi1,3 1Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Otolaryngology Head & Neck Surgery, The Second People’s Hospital of Shenzhen, Shenzhen, Guangdong, People’s Republic of China; 3Department of Allergy, Shandong Second Provincial General Hospital, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Tao Li; Yu-Zhu Wan, Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Duanxing West Road, Jinan, Shandong, 250033, People’s Republic of China, Tel +86 531 83086279 ; +86 531 83086280, Fax +86 531 87980304, Email ltwfmc@163.com; wanyuzhu001@126.comBackground: Mounting research indicates that brain-derived neurotrophic factor (BDNF), has great potential to increase neuro-hyperresponsiveness and airway resistance in airway allergic disease. The expression level of BDNF has been found to be notably elevated in lung/nasal lavage (NAL) fluid. However, the expression and position of BDNF in ciliated cells with allergic rhinitis remains unclear.Methods: Nasal mucosal cells were collected from patients with allergic rhinitis (AR) and mice which were performed under different allergen challenge time, then observed the expression and position of BDNF located in ciliated cells through the immunofluorescence staining. Nasal mucosa, serum and NAL fluid were collected also. The expression level of BDNF and IL-4/5/13 were detected by RT-PCR. The expressions of BDNF (in serum and NAL fluid), and total-IgE, ovalbumin sIgE (in serum) were detected by ELISA.Results: We found that MFI of BDNF in AR group’s ciliated cells was obviously lower than that in the control group, and a negative correlation was discovered between MFI and VAS score. It can be roughly divided into 5 patterns according to its location in the cytoplasm of ciliated cells. In the mouse model, the expressions of BDNF in serum and NAL fluid increased temporarily after allergen stimulation. The MFI of BDNF in ciliated cells displayed an initial increase followed by a subsequent decrease.Conclusion: Our study shows for the first time that, the expression and localization of BNDF were observed in the human nasal ciliated epithelial cells of allergic rhinitis, and the expression of level was less than the control group under the persistent state of allergy. BDNF expression in ciliated cells was transient increased after allergen stimulation and decreased to normal level after 24h in mouse model of allergic rhinitis. This might be the possible source of the transient increase of BNDF in serum and NAL fluid.Keywords: allergic rhinitis, BDNF, ciliated cell, NAL fluid

Yan-Fen Tang,1,2,* Jun-Yan Han,2– 4,* Ai-Min Ren,1,2 Li Chen,1,2 Tian-Jiao Xue,1,2 Yong-Hong Yan,2– 4 Xi Wang,2– 4 Yu Wang,1,2 Rong-Hua Jin2,3,5 1Department of Respiratory, Beijing Ditan Hospital Capital Medical University, Beijing, 100015, People’s Republic of China; 2National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 3Institute of Infectious Diseases, Beijing Key Laboratory of Emerging Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 4Beijing Institute of Infectious Diseases, Beijing, 100015, People’s Republic of China; 5Changping Laboratory, Beijing, 102299, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rong-Hua Jin, National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, No. 8, Jingshun Dongjie, Chaoyang District, Beijing, 100015, People’s Republic of China, Tel +86 10 84322009, Fax +86 10 84322146, Email ronghuajin@ccmu.edu.cn Yu Wang, Department of Respiratory, Beijing Ditan Hospital, Capital Medical University, No. 8, Jingshun Dongjie, Chaoyang District, Beijing, 100015, People’s Republic of China, Tel +86 10 84322963, Fax +86 10 84322146, Email wangyu20171021@163.comObjective: To explore the long-term effects of SARS-Cov-2 infection on the pulmonary function in the severe convalescent COVID-19 patients for 6 to 9 months follow-up in Beijing, China.Methods: A total of 64 cases of COVID-19 patients were recruited for the study and discharged from the Beijing Ditan Hospital, Capital Medical University, for 6 to 9 months. COVID-19 patients were divided into non-severe (mild and moderate) and severe groups. The follow-up investigated the lung function tests, the novel coronavirus antibody (IgM and IgG), chest CT and blood tests.Results: About 25.00% (16/64) patients had pulmonary ventilation dysfunction and 35.9% (23/64) had diffusion dysfunction. In the severe group, 56.50% (13/23) individuals showed decreased diffusion function. The diffusion dysfunction of the severe group was significantly decreased than the non-severe group (P = 0.01). Among 56 cases, the positive rate of IgG titers was 73.2% (41/56). The result of chest CT showed 55.36% (31/56) cases in nodules, 44.64% (25/56) in strip-like changes, 37.5% (21/56) in-ground glass shadow, and 5.36% (3/56) in grid shadow, which was significantly different between the severe group and the non-severe group. Patients tended to have ground glass changes in the severe group while nodules in the non-severe group.Conclusion: For the 6 to 9 months in convalescent COVID-19 patients, 56.50% (13/23) of severe patients had pulmonary diffusion dysfunction. Convalescent COVID-19 patients should have their pulmonary function regularly tested, especially those with severe illness.Keywords: COVID-19, pulmonary function, SARS-CoV-2 antibody, severe patients, chest CT, follow-up

The low pH of gastric acid kills unwanted microorganisms, in turn affecting their inhabitation in the intestine. Hence, studies on the factors that influence antibiotic resistance gene (ARG) propagation in the gastrointestinal tract and on the underlying mechanisms are limited.

Background: Infected pancreatic necrosis (IPN) accounts for 30% mortality in severe acute pancreatitis (SAP). Early prediction of IPN occurrence is critical for prophylactic measures to be taken. This study aimed to evaluate the predicting value for IPN of combined markers at early stages of SAP. Methods: The clincial records of 324 SAP patients admitted within 48 hours after disease onset were retrospectively analyzed. As potential predictors, the neutrophil to lymphocyte ratio (NLR), blood procalcitonin concentration (PCT) on the 1st, 4th and 7th day post admission, as well as modified computerized tomography severity index (MCTSI) on the 5 – 7th day post admission, were extracted. Correlations between these features with IPN were analyzed using logistic regression, and predictive values were estimated using the Receiver operating characteristic (ROC) curve analyses. Results: NLR, PCT, body mass index (BMI) and MCTSI were significantly higher in IPN group (p < 0.001) compared to the control, among which NLR, PCT and MCTSI were identified as independent predictors for IPN in logistic regression model. Combination of these parameters yielded signficant predicting valuse with an area under curve (AUC) of 0.92, sensitivity of 97.2% and specificity of 77.2% in ROC curve analysis. Conclusion: Combination of NLR, PCT, MCTSI might facilitate the prediction of IPN occurrence in SAP patients.

IntroductionLimitation of pharmaceutical application of resveratrol (RSV) and piceatannol (PIC) continue to exist, there is a need to obtain the superior analogs of two stilbenes with promoted activity, stability, and bioavailability. Microbial transformation has been suggested as a common and efficient strategy to solve the above problems.MethodsIn this study, Beauveria bassiana was selected to transform RSV and PIC. LC-MS and NMR spectroscopies were used to analyze the transformed products and identify their structures. The biological activities of these metabolites were evaluated in vitro with GPR119 agonist and insulin secretion assays. Single factor tests were employed to optimize the biotransformation condition.ResultsThree new methylglucosylated derivatives of PIC (1–3) and two known RSV methylglucosides (4 and 5) were isolated and characterized from the fermentation broth. Among them, 1 not only showed moderate GPR119 agonistic activity with 65.9%, but also promoted insulin secretion level significantly (12.94 ng/mg protein/hour) at 1 μM. After optimization of fermentation conditions, the yield of 1 reached 45.53%, which was increased by 4.2-fold compared with the control.DiscussionOur work presents that 3-O-MG PIC (1), obtained by microbial transformation, is an effective and safer ligand targeting GPR119, which lays a foundation for the anti-diabetic drug design in the future.

Pancreatic ductal adenocarcinoma (PDAC) usually presents infrequent infiltration of T lymphocytes. The known immune-checkpoint inhibitors to date focus on activating T cells and manifest limited effectiveness in PDAC. SIGLEC15 was identified as a novel tumor-associated macrophage (TAM)-related immune-checkpoint in other cancer types, while its immunosuppressive role and clinical significance remained unclear in PDAC. In our study, SIGLEC15 presented immunosuppressive relevance in PDAC via bioinformatic analysis and expressed on TAM and PDAC cells. SIGLEC15

Inefficient electrocatalysts and high-power consumption are two thorny problems for electrochemical hydrogen (H2) production from acidic water electrolysis. Herein we report the one-pot precise synthesis of ultrafine Au core-PtAu alloy shell nanowires (Au@PtxAu UFNWs). Among them, Au@Pt0.077Au UFNWs exhibit the best performance for formic acid oxidation reaction (FAOR) and hydrogen evolution reaction (HER), which only require applied potentials of 0.29 V and −22.6 mV to achieve a current density of 10 mA cm−2, respectively. The corresponding formic acid electrolyzer realizes the electrochemical H2 production at a voltage of only 0.51 V with 10 mA cm−2 current density. Density functional theory (DFT) calculations reveal that the Au-riched PtAu alloy structure can facilitates the direct oxidation pathway of FAOR and consequently elevates the FAOR activity of Au@Pt0.077Au UFNWs. This work provides meaningful insights into the electrochemical H2 production from both the construction of advanced bifunctional electrocatalysts and the replacement of OER.

Sulfur vacancies on MoS2 enhanced the activation of peroxymonosulfate to remove organic pollutants in wastewater.

Strain preservation to maintain stable vitality and the recombinant enzyme activity plays a crucial role in industrial fermentation. A Pichia pastoris strain is routinely stored at −80 °C in a glycerol vial and activated on an antibiotic-containing YPD agar plate before being used for fermentation. Alternatively, the activated strain should be preserved in the agar slant at 2~4 °C (low-temperature storage) for a short period before use. To maximize the utilization of the low-temperature storage for fermentation, we evaluated this method by observing the capacity of both the vitality and the recombinant enzyme activity of the strain at different preservation durations. We found that engineered yeast could be preserved by low-temperature storage for at least 30 months without losing its vitality and biomass enzyme activity by the end of fermentation and could be directly used for the seed cultivation of fermentation, which is more time-saving than strain recovery from −80 °C in a glycerol vial. Moreover, the antibiotic added to the agar slant could be omitted if the heterologous gene was integrated into the host chromosome. Our approach may greatly elevate the production efficiency of the strain.

Significant anomalous hydrogeochemical changes in hot spring water are detected during strong seismic cycles. It is now necessary to clarify the relationship between tectonic movements, earthquakes and the evolution of hot springs. In this paper, laboratory analyses of major, trace elements, δD, δ18O and 87Sr/86Sr values of 28 hot spring waters in the Jinshajiang fault zone (JSJFZ) in the northwestern boundary of the Sichuan-Yunnan block were conducted. The results showed that the primary source of water for JSJFZ hot springs was atmospheric precipitation. The geothermal reservoir temperature variation based on the silicon enthalpy mixing model ranged from 73 to 272°C. And the circulation depth range was 1.2–5.4 km. The segmentation characteristics of the 87Sr/86Sr values were related to the influence of source rocks on groundwater cycle processes. A conceptual model of the hydrologic cycle of hot springs explained the spatial distribution of earthquakes associated with tectonic movements. The Batang segment had the strongest water-rock reaction, the highest reservoir temperature and the deepest circulation depth; meanwhile, it was also an earthquake prone area. The fluid circulation of the JSJFZ corresponds well with the seismicity, which indicates that the hydrological characteristics of the hot spring water in a fracture zone play a crucial role in receiving information on seismic activity.

We have theoretically studied the field-strength dependent high-harmonic generation (HHG) in doped systems like nano-size or bulk materials. Our results show when the amplitude of the vector potential A_peak of the driving laser reaches the half-width of the Brillouin zone ({\pi}/a0), the harmonic yield of the undoped systems is larger than the doped systems. The band-climbing process enhances the interband transition of HHG for higher conduction bands. When A_peak is below {\pi}/a0 , the harmonic yield of the doped systems is stronger than the undoped systems. The atomic doping density also influences the field-strength dependent spectra., Comment: 10 pages

Objective: To study the safety and efficacy of denervation of renal artery branches in the treatment of resistant hypertension. Methods: Sixty patients with resistant hypertension were enrolled. The patients were randomly assigned to the main renal artery plus branch ablation group or the main renal artery ablation group. The clinical data and operation-related parameters, including number of ablation points, temperature, and average energy, were recorded. Ambulatory blood pressure was taken for all patients at the baseline and at 6 months after treatment. Office blood pressure was recorded before treatment and after treatment every 3 months for 2 years. Results: Sixty patients with resistant hypertension were enrolled in this study. There were 30 patients in each group. Angiography was performed after ablation. No renal artery complications, such as stenosis and dissection, occurred in the two groups. There was no significant difference in age, sex, BMI, comorbid disease, and medication between the two groups (P>0.05). The number of ablation points for the main renal artery plus branch ablation group was greater than that for the main renal artery ablation group. The office blood pressure and 24-hour blood pressure were significantly lower 6 months after treatment than before treatment in both groups (P Conclusion: The results of this study show that main renal artery plus branch ablation is a safe interventional method, but there was no obvious advantage on long-term follow-up compared with only main renal artery ablation.

Acute pancreatitis (AP) is an inflammatory disease of the pancreas. A growing number of studies have shown that long noncoding RNAs (lncRNAs) play an important role in AP progression. Here, we aimed to elucidate the role of Small Nucleolar RNA Host Gene 11(SNHG11) and its underlying molecular mechanisms behind AP progression. The in vivo and in vitro AP cell models were established by retrograde injection of sodium taurocholate and caerulein stimulation into AR42J cells and HPDE6-C7 cells, respectively. A bioinformatics website predicted the relationship between SNHG11, miR-7-5p, and Phospholipase C Beta 1(PLCB1) and validated it with a dual-luciferase reporter assay and an RNA immunoprecipitation (RIP) assay. AR42J cells and HPDE6-C7 cells were transfected with an overexpression of plasmids or shRNA to investigate the effects of the SNHG11/miR-7-5p/PLCB1 axis on cell proliferation and apoptosis, inflammatory cytokine secretion, and acute pancreatitis. Low expression of SNHG11 and PLCB1 and high expression of miR-7-5p were observed in AP pancreatic tissue and AP cell models. SNHG11 overexpression inhibited apoptosis and inflammatory responses induced by caerulein. Simultaneously, we discovered that SNHG11 regulates PLCB1 expression by sponging miR-7-5p. PLCB1 overexpression abrogated inflammatory damage exacerbated by miR-7-5p enrichment. In addition, the SNHG11/miR-7-5p/PLCB1 axis could be involved in caerulein-induced inflammatory injury by participating in the p38MAPK signaling pathway. The overexpressed SNHG11/miR-7-5p/PLCB1 axis can inhibit AP progression by participating in the p38MAPK signaling pathway, thereby providing a potential therapeutic target and therapeutic direction for AP therapy.

Mitochondrial heterogeneity above the biochemical threshold (~50% damaged mitochondria load) induces the symptom manifest of multiple mitochondrial diseases without effective treatment. However, current mitochondria-targeted therapies related to mitochondrial heterogeneity regulation have yielded unsatisfactory clinical incomes due to the risk of damaged mitochondria carryover and the imbalance of mitochondrial homeostasis. Here, we show that engineered mitochondria (Mitochondria-Lipo@mParkin, MLPers) constructed by adhesion of mitophagy-mediated liposomes to the surface of exogenous mitochondria can supply healthy mitochondria via exogenous mitochondria and both remove damaged mitochondria via enhanced mitophagy. MLPers decrease the high level of mitochondrial heterogeneity to less than 30% which is obviously lower than their biochemical threshold, and lead to the reversion of disease-related phenotypes in two mouse models of tricky mitochondrial diseases (Leber’s hereditary optic neuropathy and idiopathic pulmonary fibrosis). The surface adhesion-engineered mitochondria are powerful tools for maintaining homeostasis of mitochondrial pool and offer a translational approach for pan-mitochondrial disease therapies.

Ferroptosis is a type of programmed cell death caused by the iron-dependent lipid hydroperoxide pathway and has attracted significant interest. However, Fenton reaction-dependent ferroptosis has shown unsatisfactory therapeutic effects in tumor therapy, mainly due to inadequate reaction conditions in the tumor microenvironment. Here, we report a new strategy for Fenton-independent pathway by employing photothermal nanozyme to overcome limitations of the low efficiency of Fenton reaction. Specifically, we used iron redox pair (Fe2+/Fe3+)-containing hollow mesoporous Prussian blue (HMPB) nanocubes as the iron sources to fabricate iron-loaded liposome (HMPB@Lip). HMPB@Lip not only exerts the photothermal therapy, but also functions as nanozyme catalyzing lipid peroxidation for ferroptosis therapy. Importantly, Fenton reaction-independent ferroptosis triggered by photothermal nanozyme achieved effective tumor ablation. Therefore, HMPB@Lip can be used as a potential multifunctional nanozyme for effective Fenton reaction-independent ferroptosis therapy.

10-Deacetylbaccatin III (10-DAB) C10 acetylation is an indispensable procedure for Taxol semi-synthesis, which often requires harsh conditions. 10-Deacetylbaccatin III-10-β-O-acetyltransferase (DBAT) catalyzes the acetylation but acetyl-CoA supply remains a key limiting factor. Here we refactored the innate biosynthetic pathway of acetyl-CoA in Escherichia coli and obtained a chassis with acetyl-CoA productivity over three times higher than that of the host cell. Then, we constructed a microbial cell factory by introducing DBAT gene into this chassis for efficiently converting 10-DAB into baccatin III. We found that baccatin III could be efficiently deacetylated into 10-DAB by DBAT with CoASH and K+ under alkaline condition. Thus, we fed acetic acid to the engineered strain both for serving as a substrate of acetyl-CoA biosynthesis and for alleviating the deacetylation of baccatin III. The fermentation conditions were optimized and the baccatin III titers reached 2, 3 and 4.6 g/L, respectively, in a 3-L bioreactor culture when 2, 3 and 6 g/L of 10-DAB were supplied. Our study provides an environment-friendly approach for the large scale 10-DAB acetylation without addition of acetyl-CoA in the industrial Taxol semi-synthesis. The finding of DBAT deacetylase activity may broaden its application in the structural modification of pharmaceutically important lead compounds., Graphical abstract To acetylate 10-deacetylbaccatin III for producing baccatin III, we refactored acetyl-CoA biosynthetic pathway and combined acetyltransferase DBAT in Escherichia coli. By supplying 6 g/L 10-DAB, baccatin III reached 4.6 g/L.Image 1

The catalytic/electrocatalytic performance of platinum (Pt) nanostructures highly relates to their morphology. Herein, we propose a facile self-template pyrolysis strategy at high temperature to synthesize one-dimensionally holey Pt nanotubes (Pt-hNTs) using PtII-dimethylglyoxime complex (PtII-DMG) nanorods as the reaction precursor. The coordination capability of DMG results in the generation of PtII-DMG nanorods, whereas the reducibility of DMG at high temperature leads to the reduction of PtII species in PtII-DMG nanorods. During the reaction process, the inside-out Ostwald ripening phenomenon leads to the hollow morphology of Pt-hNTs. Benefiting from the physical characteristics of hollow and holey structure, Pt-hNTs with clean surface show superior electroactivity and durability for catalyzing ethanol electrooxidation as well as hydrogen evolution reaction in alkaline media. Under optimized experimental conditions, the constructed symmetric Pt-hNTs||Pt-hNTs ethanol electrolyzer only requires an electrolysis voltage of 0.40 V to achieve the electrochemical hydrogen production, demonstrating a highly energy saving strategy relative to traditional water electrolysis.