[The experience on the construction of the cluster prevention and control system for COVID-19 infection in designated hospitals during the period of "Category B infectious disease treated as Category A"].

The COVID-19 epidemic has spread to the whole world for three years and has had a serious impact on human life, health and economic activities. China's epidemic prevention and control has gone through the following stages: emergency unconventional stage, emergency normalization stage, and the transitional stage from the emergency normalization to the "Category B infectious disease treated as Category B" normalization, and achieved a major and decisive victory. The designated hospitals for prevention and control of COVID-19 epidemic in Tianjin has successfully completed its tasks in all stages of epidemic prevention and control, and has accumulated valuable experience. This article summarizes the experience of constructing a hospital infection prevention and control system during the "Category B infectious disease treated as Category A" period in designated hospital. The experience is summarized as the "Cluster" hospital infection prevention and control system, namely "three rings" outside, middle and inside, "three districts" of green, orange and red, "three things" before, during and after the event, "two-day pre-purification" and "two-director system", and "one zone" management. In emergency situations, we adopt a simplified version of the cluster hospital infection prevention and control system. In emergency situations, a simplified version of the "Cluster" hospital infection prevention and control system can be adopted. This system has the following characteristics: firstly, the system emphasizes the characteristics of "cluster" and the overall management of key measures to avoid any shortcomings. The second, it emphasizes the transformation of infection control concepts to maximize the safety of medical services through infection control. The third, it emphasizes the optimization of the process. The prevention and control measures should be comprehensive and focused, while also preventing excessive use. The measures emphasize the use of the least resources to achieve the best infection control effect. The fourth, it emphasizes the quality control work of infection control, pays attention to the importance of the process, and advocates the concept of "system slimming, process fattening". Fifthly, it emphasizes that the future development depends on artificial intelligence, in order to improve the quality and efficiency of prevention and control to the greatest extent. Sixth, hospitals need to strengthen continuous training and retraining. We utilize diverse training methods, including artificial intelligence, to ensure that infection control policies and procedures are simple. We have established an evaluation and feedback mechanism to ensure that medical personnel are in an emergency state at all times.

Chaihu Guizhi Ganjiang Decoction attenuates nonalcoholic steatohepatitis by enhancing intestinal barrier integrity and ameliorating PPARα mediated lipotoxicity.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a prominent cause of liver-related death that poses a threat to global health and is characterized by severe hepatic steatosis, lobular inflammation, and ballooning degeneration. To date, no Food and Drug Administration-approved medicine is commercially available. The Chaihu Guizhi Ganjiang Decoction (CGGD) shows potential curative effects on regulation of blood lipids and blood glucose, mitigation of organism inflammation, and amelioration of hepatic function. However, the overall regulatory mechanisms underlying its effects on NASH remain unclear. PURPOSE: This study aimed to investigate the efficiency of CGGD on methionine- and choline-deficient (MCD)-induced NASH and unravel its underlying mechanisms. METHODS: A NASH model of SD rats was established using an MCD diet for 8 weeks, and the efficacy of CGGD was evaluated based on hepatic lipid accumulation, inflammatory response, and fibrosis. The effects of CGGD on the intestinal barrier, metabolic profile, and differentially expressed genes (DEGs) profile were analyzed by integrating gut microbiota, metabolomics, and transcriptome sequencing to elucidate its mechanisms of action. RESULTS: In MCD-induced NASH rats, pathological staining demonstrated that CGGD alleviated lipid accumulation, inflammatory cell infiltration, and fibrosis in the hepatic tissue. After CGGD administration, liver index, liver weight, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) contents, liver triglycerides (TG), and free fatty acids (FFAs) were decreased, meanwhile, it down-regulated the level of proinflammatory mediators (TNF-α, IL-6, IL-1ß, MCP-1), and up-regulated the level of anti-inflammatory factors (IL-4, IL-10), and the expression of liver fibrosis markers TGFß, Acta2, Col1a1 and Col1a2 were weakened. Mechanistically, CGGD treatment altered the diversity of intestinal flora, as evidenced by the depletion of Allobaculum, Blautia, norank_f_Erysipelotrichaceae, and enrichment of the probiotic genera Roseburia, Lactobacillus, Lachnoclostridium, etc. The colonic histopathological results indicated that the gut barrier damage recovered in the CGGD treatment group, and the expression levels of colonic short-chain fatty acids (SCFAs)-specific receptors FFAR2, FFAR3, and tight junction (TJs) proteins ZO-1, Occludin, Claudin-1 were increased compared with those in the model group. Further metabolomic and transcriptomic analyses suggested that CGGD mitigated the lipotoxicity caused by glycerophospholipid and eicosanoid metabolism disorders by decreasing the levels of PLA2G4A, LPCAT1, COX2, and LOX5. In addition, CGGD could activate the inhibitory lipotoxic transcription factor PPARα, regulate the proteins of FABP1, APOC2, APOA2, and LPL to promote fatty acid catabolism, and suppress the TLR4/MyD88/NFκB pathway to attenuate NASH. CONCLUSION: Our study demonstrated that CGGD improved steatosis, inflammation, and fibrosis on NASH through enhancing intestinal barrier integrity and alleviating PPARα mediated lipotoxicity, which makes it an attractive candidate for potential new strategies for NASH prevention and treatment.

Integration of metabolomics and transcriptomics reveals that Da Chuanxiong Formula improves vascular cognitive impairment via ACSL4/GPX4 mediated ferroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Da Chuanxiong Formula (DCX) is a traditional herbal compound composed of Gastrodia elata Bl. and Ligusticum chuanxiong Hort, which could significantly enhance blood circulation and neuroprotection, showing promise in treating Vascular Cognitive Impairment (VCI). AIM OF STUDY: This study aims to elucidate the potential of DCX in treating VCI and its underlying mechanism. MATERIALS AND METHODS: Firstly, the cognitive behavior level, blood flow changes, and brain pathology changes were evaluated through techniques such as the Morris water maze, step-down, laser speckle, coagulation analysis, and pathological staining to appraise the DCX efficacy. Then, the DCX targeting pathways were decoded by merging metabolomics with transcriptomics. Finally, the levels of reactive oxygen species (ROS), Fe2+, and lipid peroxidation related to the targeting signaling pathways of DCX were detected by kit, and the expression levels of mRNAs or proteins related to ferroptosis were determined by qPCR or Western blot assays respectively. RESULTS: DCX improved cognitive abilities and cerebral perfusion significantly, and mitigated pathological damage in the hippocampal region of VCI model rats. Metabolomics revealed that DCX was able to call back 33 metabolites in plasma and 32 metabolites in brain samples, and the majority of the differential metabolites are phospholipid metabolites. Transcriptomic analysis revealed that DCX regulated a total of 3081 genes, with the ferroptosis pathway exhibiting the greatest impact. DCX inhibited ferroptosis of VCI rates by decreasing the levels of ferrous iron, ROS, and malondialdehyde (MDA) while increasing the level of superoxide dismutase (SOD) and glutathione (GSH) in VCI rats. Moreover, the mRNA and protein levels of ACSL4, LPCAT3, ALOX15, and GPX4, which are related to lipid metabolism in ferroptosis, were also regulated by DCX. CONCLUSION: Our research findings indicated that DCX could inhibit ferroptosis through the ACSL4/GPX4 signaling pathway, thereby exerting its therapeutic benefits on VCI.

Recent Advances and Challenges in Enzymatic Depolymerization and Recycling of PET Wastes.

Poly (ethylene terephthalate) (PET) is one of the most commonly used plastics in daily life and various industries. Enzymatic depolymerization and recycling of post-consumer PET (pc-PET) provides a promising strategy for the sustainable circular economy of polymers. Great protein engineering efforts have been devoted to improving the depolymerization performance of PET hydrolytic enzymes (PHEs). In this review, we first discuss the mechanisms and challenges of enzymatic PET depolymerization. Subsequently, we summarize the state-of-the-art engineering of PHEs including rational design, machine learning, and directed evolution for improved depolymerization performance, and highlight the advances in screening methods of PHEs. We further discuss several factors that affect the enzymatic depolymerization efficiency. We conclude with our perspective on the opportunities and challenges in bio-recycling and bio-upcycling of PET wastes.

Course and clinical severity of the SARS-CoV-2 Omicron variant infection in Tianjin, China.

There is limited information describing the course and severity of illness in subjects infected by the severe acute respiratory syndrome coronavirus 2 Omicron variant, especially in children. In this population-based cohort study, subjects with Omicron variant infection during the outbreak between January 8 and February 12, 2022 in Tianjin, China were included (n = 429). The main outcomes were the distribution of asymptomatic, mild, moderate, and severe patients, and clinical courses including the interval from positive polymerase chain reaction (PCR) test to the onset, aggravation or relief of symptoms, and the interval of reversing positive PCR-test into negative, and length of hospital stay. Of the 429 subjects (113 [26.3%] children; 239 [55.7%] female; median age, 36 years [interquartile range 15.0 to 55.0 years]), the proportion (95% CI) of symptomatic subjects on admission was 95.6% (93.2%, 97.2%), including 60.4% (55.7%, 64.9%) mild, 35.0% (30.6%, 39.6%) moderate, and 0.2% (0.0%, 1.3%) severe. Compared with adults, children had lower proportion of moderate Covid-19 (8.8% vs 44.3%). On discharge, 45.9% (41.3%, 50.7%) and 42.2% (37.6%, 46.9%) of the subjects were diagnosed as having experienced mild and moderate Covid-19. The median (interquartile range) length of hospital stay was 14.0 (12.0, 15.0) days. The median interval of reversing positive PCR-test into negative was 12.0 (10.0, 13.0) days. Symptomatic and moderate Covid-19 in Omicron infections was common in adults and children, recovery from Omicron infections took around 2 weeks of time. The severe acute respiratory syndrome coronavirus 2 Omicron infection in this study was not as mild as previously suggested.

Chitosan-coated miconazole as an effective anti-inflammatory agent for the treatment of postoperative infections in obstetrics and vaginal yeast infection control on in vitro evaluations.

People with immune deficiency are at risk of developing infections caused by several bacterial and fungal species. In this work, chitosan-coated miconazole was developed by a simple sol-gel method. Miconazole is considered an effective drug to treat vaginal infection-causing bacteria and fungi. The coating of chitosan with miconazole nitrate showed the highest drug loading efficiency (62.43%) and mean particle size (2 µm). FTIR spectroscopic analysis confirmed the entrapment of miconazole nitrate into chitosan polymer. The antifungal result demonstrated that MN@CS microgel possessed notable anti-Aspergillus fumigatus and Candida albicans activity in lower doses. Antibacterial activity results revealed excellent bacterial growth inhibition of MN@CS microgel towards human skin infectious pathogens Escherichia coli and Staphylococcus aureus. The biocompatibility studies of In vitro cell viability and Artemia salina lethality assay suggested that MN@CS microgel is more biosafe and suitable for human external applications. In the future, it will be an efficient anti-inflammatory agent for the treatment of vaginal infections.

Complete Depolymerization of PET Wastes by an Evolved PET Hydrolase from Directed Evolution.

PETase displays great potential in PET depolymerization. Directed evolution has been limited to engineer PETase due to the lack of high-throughput screening assay. In this study, a novel fluorescence-based high-throughput screening assay employing a newly designed substrate, bis (2-hydroxyethyl) 2-hydroxyterephthalate (termed BHET-OH), was developed for PET hydrolases. The best variant DepoPETase produced 1407-fold more products towards amorphous PET film at 50 °C and showed a 23.3 °C higher Tm value than the PETase WT. DepoPETase enabled complete depolymerization of seven untreated PET wastes and 19.1 g PET waste (0.4 % Wenzyme /WPET ) in liter-scale reactor, suggesting that it is a potential candidate for industrial PET depolymerization processes. The molecular dynamic simulations revealed that the distal substitutions stabilized the loops around the active sites and transmitted the stabilization effect to the active sites through enhancing inter-loop interactions network.

'Dynamic zero-COVID' policy and viral clearance during an omicron wave in Tianjin, China: a city-wide retrospective observational study.

OBJECTIVE: To report how the Chinese mainland battled its first omicron wave, which happened in Tianjin, a metropolis with 14 million residents. We also sought to better understand how clinical features affected the timing of viral clearance. DESIGN: A retrospective study of the omicron wave in Tianjin between 8 January 2022 and 3 March 2022. SETTING: Except for the first cases on 8 January, all the omicron cases were identified through PCR mass testing in the residential communities. Residential quarantine and serial PCR mass testing were dynamically adjusted according to the trends of new cases. PARTICIPANTS: All the 417 consecutive PCR-positive cases identified through mass screening of the entire city's 14 million residents. 45.3% of the cases were male, and the median age was 37 (range 0.3-90). 389 (93%) cases had complete data for analysing the correlation between clinical features and the timing of viral clearance. MAIN OUTCOME AND MEASURE: Time to viral clearance. RESULTS: Tianjin initiated the 'dynamic zero-COVID' policy very early, that is, when daily new case number was ≈0.4 cases per 1 000 000 residents. Daily new cases dropped to <5 after 3 February, and the number of affected residential subdivisions dropped to ≤2 after 13 February. 64% (267/417) of the cases had no or mild symptoms. The median interval from hospital admission to viral clearance was 10 days (range 3-28). An exploratory analysis identified a feature cluster associated with earlier viral clearance, with HRs of 3.56 (95% CI 1.66 to 7.63) and 3.15 (95% CI 1.68 to 5.91) in the training and validation sets, respectively. CONCLUSIONS: The 'dynamic zero-COVID' policy can suppress an omicron wave within a month. It might be possible to predict in advance which cases will require shorter periods of isolation based on their clinical features.

Viral RNA Load in Symptomatic and Asymptomatic COVID-19 Omicron Variant-Positive Patients.

Objectives: Viral load is important when evaluating viral transmission potential, involving the use of a polymerase chain reaction (PCR) cycle threshold (Ct) value. We aimed to analyze the PCR Ct values of respiratory tract samples taken from patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant strains to evaluate these strains' viral dynamics. Methods: This study comprised 361 patients. The Ct values of SARS-CoV-2-related respiratory samples were compared between symptomatic and asymptomatic patients. Results: The median (25th percentile and 75th percentile) nasopharynx and oropharynx SARS-CoV-2 Ct values were 30.5 (24.5-35.0) and 34.5 (30.0-37.0) in the symptomatic group, respectively, and 27.8 (23.4-34.5) and 33.5 (26.0-35.0) in the asymptomatic group, respectively, without significance. In the symptomatic group, subgroup analyses according to age showed the mean nasal Ct value for patients aged >18 years was 29.0 (23.5-34.5), which was significantly lower than that of patients aged 0-4 years and 5-13 years (36.0 (30.5-38.0) and 34.5 (31.0-39.0), respectively). The nasal Ct value for asymptomatic patients aged >18 years was 25.5 (20.9-28.4), which was significantly lower than of patients aged 5-13 years (34.5 (25.6-36.4)). Conclusion: Our findings suggest that the viral loads of asymptomatic and symptomatic patients did not differ significantly. However, adults infected with SARS-CoV-2 had higher nasal viral loads that those of young children.

The Relation between Immunological Features and the Positive SARS-CoV-2 Nucleic Acid in Patients with Nonsevere COVID⁃19.

Objective: The novel coronavirus nucleic acid results are the core indicators of illness monitoring. This study aimed to evaluate the relationship between immunological features and positive SARS-CoV-2 nucleic acid by analyzing the clinical and immunological features in nonsevere COVID-19 cases. Methods: Data from nonsevere COVID-19 patients admitted to Haihe Hospital from May 2020 to June 2021 were retrospectively reviewed and analyzed. Results: (1) A total of 122 cases were reviewed in the present study, including 38 mild and 84 moderate cases. The average age of mild cases was significantly different from moderate cases (P < 0.001). Eight patients complained of hyposmia and it was more frequent in mild cases (P < 0.001). The nucleic acid positive duration (NPD) of nonsevere novel coronavirus was 20.49 (confidence interval (CI) 17.50-3.49) days. (2) The levels of specific IgM and IgG for COVID-19 were higher in mild cases than in moderate cases (P=0.023 and P=0.047, respectively). (3) The correlation analysis with antibodies and T-cell subtypes showed that the lymphocyte (LYM) count, T cells, CD4+T cells, and CD8+T cells had a linear correlation with NPD. (4) Among the 93 patients monitored, 62 COVID-19 cases presented a progressive rise of specific IgM and IgG. The daily increase rates of IgM and IgG were 38.42% (CI 28.22-48.61%) and 24.90% (CI 0.23-29.58%), respectively. Conclusion: The levels and daily increase rates of specific IgM and IgG against the virus can vary between cases. The NPD presented a linear correlation with the LYM, T cells, CD4+T cells, and CD8+T cells. Hence, more attention should be paid to these indicators in clinical practice.

[Clinical study of awake prone positioning treatment in patients with common coronavirus disease 2019 caused by Omicron variant].

OBJECTIVE: To evaluate the clinical effect of awake prone positioning (APP) for common coronavirus disease 2019 (COVID-19) caused by Omicron variant. METHODS: Retrospectively analyze the clinical data of patients with COVID-19 caused by Omicron variant admitted by medical team of Tianjin Third Central Hospital during the period of supporting Tianjin COVID-19 designated hospital from January 8 to February 20, 2022. Patients who met the diagnostic criteria for common COVID-19 and had risk factors for developing severe disease or had pulse oxygen saturation (SpO2) ≤ 0.93 after exercise without supplementary oxygen were enrolled. Patients were divided into APP group and control group according to whether they completed the daily 12-hours APP in the first three days after enrollment. Demographic characteristics, clinical symptoms, COVID-19 vaccination status, laboratory examination, disease progression (progression to severe), time to nucleic acid negative conversion, length of hospital stay, and adverse reactions and tolerability [visual analog scale (VAS) score (the higher the score, the worse the tolerability] during APP were evaluated in two groups. Interleukin-6 (IL-6), C-reactive protein (CRP), SpO2/inhaled oxygen concentration (FiO2) ratio and ROX index (ROXI) were compared between two groups at enrollment, 3rd and 7th day after enrollment. RESULTS: There were no significant differences in demographic characteristics, clinical symptoms, vaccination rates of COVID-19 and laboratory tests between the two groups. There were no statistically significant differences in IL-6, CRP, SpO2/FiO2 ratio and ROXI between two groups at the time of enrollment. Compared with the group at the time of enrollment, SpO2/FiO2 ratio and ROXI in APP group increased significantly at the 3rd day after enrollment [SpO2/FiO2 ratio: 461.90 (457.10, 466.70) vs. 446.67 (437.14, 457.10), ROXI: 25.40 (23.33, 25.93) vs. 22.57 (21.86, 24.40), all P < 0.05], and the levels of IL-6 and CRP in control group were significantly increased [IL-6 (ng/L): 18.30 (6.50, 37.75) vs. 7.40 (5.10, 11.15), CRP (mg/L): 11.46 (2.11, 17.96) vs. 4.11 (1.72, 9.05), all P < 0.05]. At the 3rd day of enrollment, the levels of IL-6 and CRP in APP group were significantly lower than those in control group [IL-6 (ng/L): 7.35 (4.35, 12.80) vs. 18.30 (6.50, 37.75), CRP (mg/L): 4.52 (1.98, 9.66) vs. 11.46 (2.11, 17.96), all P < 0.05], while SpO2/FiO2 ratio and ROXI were significantly higher than those in control group [SpO2/FiO2 ratio: 461.90 (457.10, 466.70) vs. 446.67 (441.90, 459.52), ROXI: 25.40 (23.33, 25.93) vs. 23.31 (22.10, 24.66), all P < 0.05]. At the 7th day of enrollment,there were no significant differences in IL-6, CRP, SpO2/FiO2 ratio and ROXI between two groups. There were no severe cases in both groups. The time of nucleic acid negative conversion and length of hospital stay in APP group were significantly shorter than those in control group [10.0 (8.0, 12.0) days vs. 11.0 (9.0, 13.0) days, 12.0 (10.0, 14.0) days vs. 14.0 (12.0,16.0) days, respectively, all P < 0.05]. The main adverse reaction during APP was back pain, and the incidence in APP group was slightly lower than that in control group, but the difference was not statistically significant [17.9% (17/95) vs. 26.5% (27/102), P = 0.149]. VAS score in control group was significantly higher than that in APP group [score: 2.5 (2.0, 4.0) vs. 2.0 (1.0, 3.0), P = 0.004]. CONCLUSIONS: In common COVID-19 patients caused by Omicron variant with high risk factors for progression to severe disease or decreased oxygen reserve capacity, early APP can shorten the time of nucleic acid negative conversion and the length of hospital stay, but its effect on preventing disease progression cannot be determined.

[Analysis of clinical characteristics of 362 vaccinated or unvaccinated patients infected by novel coronavirus Omicron variant].

OBJECTIVE: To analyze the epidemiological and clinical characteristics of patients infected by novel coronavirus Omicron variant, and also to analyze whether vaccination against novel coronavirus has an impact on the severity and prognosis of Omicron patients. METHODS: A prospective, single-center observational study was conducted to collect data of consecutive patients with Omicron variant infection admitted to the designated hospital for coronavirus disease 2019 (COVID-19) charged by Tianjin COVID-19 rescue medical team of Tianjin Third Central Hospital, from January 8 to February 2, 2022. The clinical characteristics of the patients were analyzed, and the influence of whether the patients were inoculated with booster vaccination on the condition and outcome was analyzed. Data were collected including epidemiological, clinical features, laboratory and imaging examination, treatment measures and clinical outcomes, and difference between groups was analyzed. RESULTS: A total of 362 patients were included, including 136 cases (37.57%) in the booster group, 190 cases (52.49%) in the routine vaccination group, and 36 cases (9.94%) in the unvaccinated group. There was a trend of concentrated distribution of patients, of which 171 cases (47.24%) patients showed family clustering, involving 69 families. Seventy-four cases (20.44%) of the 362 patients had one or more underlying diseases, mainly hypertension (64 cases, 17.68%), diabetes mellitus (23 cases, 6.35%), and coronary heart disease (18 cases, 4.97%); 215 patients (59.39%) had one or more discomfort symptoms, mainly cough (158 cases, 43.65%), pharyngeal discomfort (154 cases, 42.54%) and fever (136 cases, 37.57%). The diagnostic typing was mild type in 194 cases (53.59%), moderate type in 165 cases (45.58%) and severe type in 3 cases (0.83%). The patients had elevated immunoglobulin G (IgG) antibody titers to the novel coronavirus on admission [23.17 (3.08, 60.77)]. Patients were medically isolated and the main treatment measures included traditional Chinese medicine identification (Chinese medicine or tonics) in 265 cases (73.20%), prone treatment in 188 cases (51.93%), anticoagulation with low-molecular heparin in 106 cases (29.28%), immunomodulatory therapy with thymofacine in 21 cases (5.80%), antimicrobial drugs in 20 cases (5.52%), transnasal high-flow oxygen therapy in 12 cases (3.31%), glucocorticoids in 5 cases (1.38%), non-invasive mechanical ventilation in 1 case (0.28%), and invasive mechanical ventilation in 1 case (0.28%). A total of 362 patients were discharged with no deaths, of which 12 patients (3.31%) were admitted to the intensive care unit (ICU). The median duration of illness was 13 (10, 15) days, the median length of hospitalization was 13 (11, 15) days, and the median time to nucleic acid conversion was 13 (10, 15) days. Compared with the unvaccinated group, the IgG antibody titers of patients in the booster and routine vaccination groups [41.49 (20.32, 81.38), 19.94 (2.33, 49.25) vs. 0.16 (0.07, 1.94)] and the proportion of mild patients [66.91% (91/136), 48.94% (93/190) vs. 27.28% (10/36)] were higher, which were also higher in the booster vaccination group than in the conventional vaccination group (all P < 0.05). Compared to the conventional and booster vaccination groups, the unvaccinated group had a higher proportion of severe patients [5.56% (2/36) vs. 0.53% (1/190), 0 (1/136)], longer time to nucleic acid conversion [days: 15 (11, 16) vs.12 (10, 15), 13 (11, 15)], and longer disease duration [days: 15 (11, 16) vs. 12 (10, 15), 13 (11, 15)], and a higher percentage of ICU admissions [16.67% (6/36) vs. 2.63% (5/190), 0.74% (1/136)], with statistically significant differences among the three groups (all P < 0.05). CONCLUSIONS: Omicron variant is extremely infectious with aggregated onset, but its clinical symptoms are mild. The vaccine, especially the booster vaccination, remains effective in preventing severe-stage progression and improving prognosis in patients with Omicron variant infection.

Case Report of China/Tianjin's First Novel Coronavirus Variant Omicron.

COVID-19 is a new acute respiratory infectious disease caused by a novel Coronavirus (2019-COV-2) infection. On November 26, 2021, the World Health Organization announced a new 2019-COV-2 variant strain Omicron (B.1.1.529). Omicron's emergence added further uncertainty to the outbreak. Here we report the first case infected with Omicron in China, a 17-year-old female student. In this paper, the clinical symptoms, laboratory and imaging examinations and treatment of the first Omicron-infected patient in China were analyzed. This report might provide a reference for the diagnosis and treatment of patients infected with Omicron strain across the world. The novel Coronavirus antibody tests were performed on the day of admission: IgM level was normal, novel Coronavirus antibody IgG was 132.666s /CO and IgG was 148.47s /CO on the 7th day of admission. IgG showed an increasing trend, which is consistent with the results of multiple novel Coronavirus non-Omicron strain infections.

Genomic deciphering of sex determination and unique immune system of a potential model species rare minnow (Gobiocypris rarus).

Gobiocypris rarus is sensitive to environmental pollution, especially to heavy metal and grass carp reovirus (GCRV). Hence, it has potential utility as a biological monitor. Genetic deciphering of its unique immune system will advance our understanding of its unique adaptive strategies, which provide cues for its better application. A de novo genome of rare minnow was obtained, and its sex determination mechanism is ZZ/ZW. We identified several specific mutation genes and specific lost genes of rare minnow, and these might be related to the sensitivity of rare minnow to environmental stimuli. We also analyzed the gene expression level of different organs/tissues and found that several IFIT genes may play key roles in GCRV resistance. In addition, knockout of the gene PCDH10L indicates that PCDH10L affects Pb2+-induced mortality in rare minnow. Rare minnow is ready for genetic manipulation and shows potential as an emerging experimental model.

SERS-Active Composites with Au-Ag Janus Nanoparticles/Perovskite in Immunoassays for Staphylococcus aureus Enterotoxins.

The accurate detection of Staphylococcus aureus enterotoxins (SEs) is vital for food safety owing to their high pathogenicity, which may be performed with surface-enhanced Raman scattering (SERS) if SERS-active nanostructures are used. Herein, a Au-Ag Janus nanoparticle (NPs)/perovskite composite-engineered SERS immunoassay was developed for SEC detection. Plasmonic Au-Ag Janus NPs demonstrated inherent SERS activity from the 2-mercaptobenzoimidazole-5-carboxylic acid ligands. CsPbBr3@mesoporous silica nanomaterials (MSNs) were prepared and transformed into CsPb2Br5@MSNs in the aqueous phase. Paired SEC antibody-antigen-driven plasmonic Au-Ag Janus NP-CsPb2Br5@MSN composites were prepared. They showed amplified SERS activity, attributed to the depressed plasmonic decay due to electromagnetic field enhancement and the electron transfer mechanism. A positive relationship was established between SERS signals of composites and the SEC concentration. An additive-free SERS immunoassay was developed for simple, sensitive, and reproducible SEC detection. This study will be extended to develop multiple additive-free SERS-active plasmonic NP/perovskite composites that will open up the possibility of exploring more SERS detection probes for food safety monitoring.

A large-scale, multicentered trial evaluating the sensitivity and specificity of digital PCR versus ARMS-PCR for detecting ctDNA-based EGFR p.T790M in non-small-cell lung cancer patients.

BACKGROUND: Developing liquid biopsy technology with higher sensitivity and specificity especially for low-frequency mutations remains crucial. This study demonstrated superior performance of the newly developed digital PCR (dPCR) kit for ctDNA-based EGFR p.T790M detection in metastatic non-small-cell lung cancer (NSCLC) against ARMS-PCR. METHODS: This large-scale, multi-centered diagnostic study recruited 1,045 patients including 1,029 patients diagnosed with advanced NSCLC and 16 patients with specific samples between April 1st 2018 and November 30th 2019. EGFR p.T790M in plasma samples from mNSCLC patients were tested using dPCR with ADx-ARMS PCR and Cobas® EGFR Mutation Test V2 as comparator assays to confirm cut-off value for dPCR and evaluate its performance against ARMS-PCR-based assays. Efficacy was evaluated for patients with EGFR p.T790M detected by dPCR or ARMS-PCR, who underwent Osimertinib treatment. RESULTS: The sensitivity, specificity, and concordance of dPCR against ADx-ARMS PCR was 98.15%, 88.66% and 90.16%, respectively for 1,026 plasma samples. Additional 9.26% patients were detected positive by dPCR. The majority of those samples had a mutation allele frequency between 0.1% and 1%. In 45 paired tissue and plasma samples, the sensitivity improved from 30.77% to 53.85% by dPCR with the specificity over 90%. The response of Osimertinib in 74 EGFR p.T790M-positive patients detected by dPCR, including 26 determined as negative by ARMS-PCR, were evaluated to have an ORR of 44.59% and a DCR of 90.54%. CONCLUSIONS: dPCR is a sensitive and accurate tool for ctDNA-based EGFR p.T790M detection due to its significantly improved sensitivity without compromising specificity, and dPCR is equivalent to ARMS-PCR as a companion diagnostic tool while benefiting more patients under Osimertinib treatment. TRIAL REGISTRATION: Chinese Clinical Trial Registry identifier: ChiCTR2100043147.

Perovskite Nanomaterial-Engineered Multiplex-Mode Fluorescence Sensing of Edible Oil Quality.

Water-soluble fluorescence nanomaterials are widely applied for water-phase food safety monitoring. However, there is still a challenge for the development of oil-soluble fluorescence nanomaterials for oil-phase food safety detection. Particularly, the edible oil quality has a huge impact on human health, in which excessive acid number (AN), 3-chloro-1,2-propanediol (3-MCPD), and moisture content (MC) are critical monitoring factors. Herein, orange-emitting oil-soluble CsPbBr1.5I1.5 quantum dots (QDs) were prepared and applied for AN and 3-MCPD detection depending on fluorescence quenching and wavelength shifts. A "turn-off" fluorescence sensor and "wavelength-shift" fluorescence colorimetric sensor were fabricated for AN and 3-MCPD detection. Water-sensitive mesoporous silica-coated CsPbBr1.5I1.5 QDs were employed for the establishment of ratiometric fluorescence sensors for MC monitoring by introducing water-stable green-emitting CsPbBr3 nanosheets (NSs) as reference probes. Perovskite nanomaterial-engineered multiplex-mode fluorescence sensors were proposed for the detection of AN, 3-MCPD, and MC in edible oil, with the limits of detection (LODs) of 0.71 mg KOH/g, 39.8 µg/mL 3-MCPD, and 0.45% MC, respectively. This work not only expands the application of perovskite nanomaterials in the bioanalysis field but also provides new materials and novel approaches for the multiplex-mode oil-phase food safety monitoring.

"Add on" Dual-Modal Optical Immunoassay by Plasmonic Metal NP-Semiconductor Composites.

Staphylococcus aureus enterotoxins (SEs, involving SEA, SEB, SEC, SED, and SEE) are considered to be the common toxins causing food poisoning and are not allowed to be detected in food. Accurate and anti-interfering SE detection in a complex food matrix is urgently required for food safety. Dual-modal optical sensors are able to avoid mutual interference of optical signals and possess the advantages of high accuracy and sensitivity. Herein, Au nanobipyramids (Au NBPs) and persistent luminescence ZnGeGaO:Cr,Er,Yb nanoparticle (ZGGO NP) nanocomposites are fabricated using the SEC antibody/antigen as templates, which display enhanced persistent luminescence (PL) and surface-enhanced Raman scattering (SERS) strength. The enhanced PL of Au NBP-ZGGO NP nanocomposites is ascribed to plasmon-enhanced radiative transitions. It is first found that ZGGO NPs display unique upconversion fluorescence, which can be absorbed by Au NBPs and that they largely excite the intensive electromagnetic field for SERS enhancement. Dual-model optical immunoassay achieved anti-interfering and specific SEC detection with a limit of detection of 7.5 pg/mL for the PL signal and 8.9 pg/mL for the SERS signal in the range of 10 pg/mL-100 ng/mL. Depending on the plasmon-enhanced PL mechanism and upconversion fluorescence-enhanced SERS principle, plasmonic NP-semiconductor composites show potential prospects in the establishment of multimodal optical biosensors for the quantitative and accurate evaluation of analytes in a complex food matrix.

Enhanced Extracellular Production of IsPETase in Escherichia coli via Engineering of the pelB Signal Peptide.

Poly(ethylene terephthalate) (PET) is one of the most commonly used plastics worldwide and its accumulation in the environment is a global problem. PETase from Ideonella sakaiensis 201-F6 was reported to exhibit higher hydrolytic activity and specificity for PET than other enzymes at ambient temperature. Enzymatic degradation of PET using PETase provides an attractive approach for plastic degradation and recycling. In this work, extracellular PETase was achieved by Escherichia coli BL21 using a Sec-dependent translocation signal peptide, pelB, for secretion. Furthermore, engineering of the pelB through random mutagenesis and screening was performed to improve the secretion efficiency of PETase. Evolved pelB enabled higher PETase secretion by up to 1.7-fold. The improved secretion of PETase led to more efficient hydrolysis of the PET model compound, bis (2-hydroxyethyl) terephthalic acid (BHET), PET powder, and PET film. Our study presents the first example of the increasing secretion of PETase by an engineered signal peptide, providing a promising approach to obtain extracellular PETase for efficient enzymatic degradation of PET.

Ratiometric persistent luminescence aptasensors for carcinoembryonic antigen detection.

NIR-emitted ZnGa2O4:Cr3+ persistent luminescence nanoparticles (ZGC NPs) coated with polydopamine (ZGC@PDA NPs) were designed featuring internal reference and quenching ability. Sr-doped Zn2GeO4 persistent luminescence nanorods (ZGO:Sr NRs) served as detection probes, which exhibited blue emission. The decay times and intensity of luminescence of ZGO:Sr NRs were optimized to acquire desired luminescence properties. An aptamer-guided ratiometric persistent luminescence sensor with the LOD (0.46 pg mL-1) was established to detect carcinoembryonic antigen (CEA). This developed ratiometric aptasensor based on persistent luminescence nanomaterials (PLMs) does not only use the afterglow properties of nanomaterials to avoid the interference of autofluorescence but also precludes the interference of certain factors in the detection environment on the luminescence intensity due to the introduction of a reference signal, and is suitable for early screening of tumor markers in serum samples. Moreover, the optimization of luminescence properties, especially for luminescence decay times, provides a way for the fabrication of multiple persistent luminescence materials in the application of time-resolved fluorescence technology. Graphical abstract Construction of ZGO:Sr NR- and ZGC@PDA NP-driven ratiometric aptasensor for CEA detection.