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Abstract Background Omicron variant impacts populations with its rapid contagiousness, and part of patients suffered from persistent symptoms termed as long COVID. The molecular and immune mechanisms of this currently dominant global variant leading to long COVID remain unclear, due to long COVID heterogeneity across populations. Methods We recruited 66 participants in total, 22 out of 66 were healthy control without COVID-19 infection history, and 22 complaining about long COVID symptoms 6 months after first infection of Omicron, referred as long COVID (LC) Group. The left ones were defined as non-long COVID (NLC) Group. We profiled them via plasma neutralizing antibody titer, SARS-CoV-2 viral load, transcriptomic and proteomics screening, and machine learning. Results No serum residual SARS-CoV-2 was observed in the participants 6 months post COVID-19 infection. No significant difference in neutralizing antibody titers was found between the long COVID (LC) Group and the non-long COVID (NLC) Group. Transcriptomic and proteomic profiling allow the stratification of long COVID into neutrophil function upregulated (NU-LC) and downregulated types (ND-LC). The NU-LC, identifiable through a refined set of 5 blood gene markers (ABCA13, CEACAM6, CRISP3, CTSG and BPI), displays evidence of relatively higher neutrophil counts and function of degranulation than the ND-LC at 6 months after infection, while recovered at 12 months post COVID-19. Conclusion The transcriptomic and proteomic profiling revealed heterogeneity among long COVID patients. We discovered a subgroup of long COVID population characterized by neutrophil activation, which might associate with the development of psychiatric symptoms and indicate a higher inflammatory state. Meanwhile, a cluster of 5 genes was manually curated as the most potent discriminators of NU-LC from long COVID population. This study can serve as a foundational exploration of the heterogeneity in the pathogenesis of long COVID and assist in therapeutic targeting and detailed epidemiological investigation of long COVID.

ABSTRACTData on reinfection in large Asian populations are limited. In this study, we aimed to evaluate the reinfection rate, disease severity, and time interval between the infections in the symptomatic and asymptomatic populations which are firstl infected with BA.2 Omicron Variant. We retrospectively included adult patients with COVID-19 discharged from four designated hospitals between 27 April 2021 and 30 November 2022, who were interviewed via telephone from 29 January to 1 March 2023. Univariable and multivariable analyses were used to explore risk factors associated with reinfection. A total of 16,558 patients were followed up, during the telephone survey of an average of 310.0 days, 1610 (9.72%) participants self-reported reinfection. The mean time range of reinfection was 257.9 days. The risks for reinfection were analysed using multivariable logistic regression. Patients with severe first infection were at higher risk for reinfection (aORs, 2.50; P

IntroductionBaloxavir Marboxil is a per oral small-molecule antiviral for the treatment of influenza. While the efficacy and safety of Baloxavir Marboxil have been thoroughly characterized across an extensive clinical trial, studies on the effectiveness of Baloxavir Marboxil in a real-world setting are still scarce.MethodsWe conducted an ambispective, observational, multi-center study that enrolled uncomplicated in-fluenza outpatients treated with Baloxavir Marboxil or Oseltamivir in East China. The primary endpoint was time from treatment to alleviation of all influenza symptoms (TTAIS). The secondary endpoints included time from treatment to alleviation of fever (TTAF) and household transmission during the duration of influenza.ResultsA total of 509 patients were enrolled. The median TTAIS in the Baloxavir Marboxil group and the Oseltamivir group was 28.0 h (IQR, 20.0 to 50.0) and 48.0 h (IQR, 30.0 to 67.0), respectively. The median TTAF in the Baloxavir Marboxil group and the Oseltamivir group was 18 h (IQR, 10.0–24.0) and 30.0 h (IQR, 19.0–48.0). In the COX multivariable analysis, Baloxavir Marboxil reduced the duration of influenza symptoms (HR = 1.36 [95%CI:1.12–1.64], p = 0.002) and the duration of fever (HR = 1.93 [95%CI:1.48–2.52], p

Background: Several respiratory infections outbreaks have been observed in mainland China after reduction of non-pharmaceutical interventions. Other countries have seen increases in respiratory infections outside typical seasons post-COVID-19, warranting investigation into underlying causes. Methods: We established monitoring networks for suspected respiratory infection in 14 tertiary hospitals nationwide. PCR for SARS-CoV-2, influenza A and B were performed on 3708 respiratory specimens and deep sequencing were conducted to identify co-infections or newly emerging microbes in 2023. Viral evolutionary analysis was completed. We retrospectively detected serum antibody level for various respiratory pathogens from 4324 adults without respiratory infections over 7 years to observe its dynamic curves. Findings: SARS-CoV-2 and influenza A were the main pathogens during outbreaks in 2023, bacterial-virus and bacterial-bacterial co-infections were most detected, but community co-infections didn't significantly increase pneumonia incidence. Different SARS-CoV-2 and influenza variants were present in different outbreaks, and no novel pathogens were found. The epidemiological patterns of influenza A, COVID-19 and etc. were altered, exhibiting characteristics of being ''staggered'' compared to most global regions, and potentially led to ''overlapping prevalence''. Binding antibody testing showed regular fluctuation, without significant decrease against common respiratory pathogens in adults. Influenza A antibody stimulation was attenuated during the 2023 outbreak. Conclusions: ''Misaligned'' alteration in seasonal respiratory disease patterns possibly caused combined epidemics, leading to cases spike in China, 2023. In adults, antibody levels didn't show significant decline, but reduced immune response to influenza during 2020–2023 emphasizes the need for consistent vaccination during pandemics.

Correctly identifying the topology of a low-voltage distribution network aids in its management by power companies. However, the low collection rate and poor quality of the customer data collected by smart meters create difficulties in the application of data analysis algorithms. To address this, a new data-driven approach is proposed for topology identification in low-voltage distribution networks. First, a linear fitting method is used to approximate the noise-containing data. Next, the t-distributed stochastic neighbor embedding (t-SNE) method is used to reduce the dimensionality of the high-dimensional time-series voltage data. Then, the density-based spatial clustering of applications with noise (DBSCAN) method is applied to cluster the reduced dimensional data to perform topology identification. Finally, the simulated data and the actual data of a low-voltage distribution network in Dongguan, Guangdong Province are analyzed, and the results show the effectiveness and practicality of the proposed method.

Abstract The phase‐locked loop (PLL) is a critical control module applied in the control system of renewable energy sources (RESs) to synchronize with the grid voltage. When a fault occurs, the dynamic response process of the PLL will generate a phase locking error, resulting in a mass of harmonic components in the fault current of the PV inverter, which further poses challenges to transformer differential protection. To address the challenges posed by the phase locking error in practical engineering applications, this paper proposes an improved scheme that uses a digital computer algorithm to record and store the pre‐fault voltage and introduces the limiting coefficient. Firstly, the memory voltage is used to eliminate the phase locking error of the PLL, thereby mitigating harmonic distortion in the fault current of the RESs and ensuring the reliability of the transformer differential protection. In addition, the limiting coefficient is introduced to eliminate the effect of the increased amplitude of the fault current caused by the memory voltage. The voltage reference value of the inverter is multiplied by an appropriate limiting coefficient k and then output to the physical system. Finally, the effectiveness of the proposed scheme is verified by MATLAB/Simulink simulation.

ABSTRACTThis study aimed to investigate the prognostic value of a novel droplet digital polymerase chain reaction (DDPCR) assay in sepsis patients. In this prospective cohort study, univariable and multivariable Cox regressions were used to assess risk factors for 28-day mortality. We also monitored pathogen load together with clinical indicators in a subgroup of the cohort. A total of 107 sepsis patients with positive baseline DDPCR results were included. Detection of poly-microorganisms [adjusted hazard ratio (HR) = 3.19; 95% confidence interval (CI) = 1.34–7.62; P = 0.009], high Charlson Comorbidity Index (CCI) score (adjusted HR = 1.14; 95% CI = 1.01–1.29; P = 0.041), and Sequential Organ Failure Assessment (SOFA) score (adjusted HR = 1.18; 95% CI = 1.05–1.32; P = 0.005) at baseline were independent risk factors for 28-day mortality while initial pathogen load was not associated (adjusted HR = 1.17; 95% CI = 0.82–1.66; P = 0.385). Among 63 patients with serial DDPCR results, an increase in pathogen load at days 6–8 compared to baseline was a risk factor for 28-day mortality (P = 0.008). Also, pathogen load kinetics were significantly different between day-28 survivors and nonsurvivors (P = 0.022), with a decline overtime only in survivors and an increase from days 3 and 4 to days 6–8 in nonsurvivors. Using DDPCR technique, we found that poly-microorganisms detected and increased pathogen load a week after sepsis diagnosis were associated with poor prognosis.IMPORTANCEThis prospective study was initiated to explore the prognostic implications of a novel multiplex PCR assay in sepsis. Notably, our study was the largest cohort of sepsis with droplet digital polymerase chain reaction pathogen monitoring to date, allowing for a comprehensive evaluation of the prognostic significance of both pathogen species and load. We found that detection of poly-microorganisms was an independent risk factors for 28-day mortality. Also, pathogen load increase 1 week after sepsis diagnosis was a risk factor for 28-day mortality, and differential pathogen load kinetics were identified between day-28 survivors and nonsurvivors. Overall, this study demonstrated that pathogen species and load were highly correlated with sepsis prognosis. Patients exhibiting conditions mentioned above face a more adverse prognosis, suggesting the potential need for an escalation of antimicrobial therapy.Registered at ClinicalTrials.gov (NCT05190861).

Abstract. The Omicron variants have continued to cause severe acute respiratory syndrome coronavirus 2 infections. To better understand the anti-viral effects of vaccination on host-virus interactions during the outbreak of BA.2.2 Omicron, we conducted RNA-seq transcriptome analysis on nasopharyngeal swabs from COVID-19 patients in Shanghai. This study was performed on selected cases from unvaccinated, fully vaccinated, and booster groups with the same founder virus infection background. We observed predominant immune cell chemotaxis and interleukin-1 production, as well as mucosal keratinization and epidermis development, in unvaccinated patients. In contrast, fully vaccinated subjects exhibited an obvious T-cell activation in the local immune response, whereas B-cell activation was higher in booster-vaccinated cases. In conclusion, our findings suggest that full or booster vaccination provides better adaptive immunity and relieve inflammation at the nasopharyngeal site, thereby reducing the risk of cytokine storm during breakthrough infection.

Abstract Aim Patients with chronic liver disease (CLD), especially cirrhosis, are at a high risk of severe illness or death from coronavirus disease‐2019 (COVID‐19) and may have a suboptimal immune response to the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccine. This study aimed to evaluate the safety and immunogenicity of the COVID‐19 booster vaccination in patients with CLD. Methods The study protocol was prospectively registered at ClinicalTrials.gov (No. NCT05204602) after approval by the Ethics Committee. Adult participants with CLD were enrolled in this multicenter prospective study. They completed two doses of the inactivated COVID‐19 vaccine and received booster doses at least 6 months later. Adverse reactions were recorded within 14 days after the booster dose. Serum samples of the enrolled patients were collected before and after booster vaccination and tested for SARS‐CoV‐2 receptor‐binding domain (RBD) immunoglobulin G and neutralizing antibodies. The chi‐squared or Fisher's exact test was used to compare categorical data, and the Mann–Whitney U test was used to compare continuous variables. Two‐sided p

IntroductionThe evaluation on the trade-off/synergy relationship of urban cultivated land-use function conflicts (CLUFCs) for improving the sustainability of cultivated land ecosystem is one of the solutions to coordinate the contradiction between land health and economic development and alleviate food crises, and achieve “zero hunger” in the United Nations Sustainable Development Goals (SDGs).MethodsIn this study, Yancheng City was taken as the research object, and the cultivated land ecological function (CLEF) was evaluated by the morphological spatial pattern analysis-minimum cumulative resistance (MSPA-MCR) model from the perspective of multi-objective coordinated development of cultivated land, and cultivated land productive function (CLPF) was evaluated by net primary productivity (NPP). In addition, combined with local indications of spatial association (LISA) analysis, the spatial trade-off/synergy relationship between CLPF and CLEF was quantified and analyzed. The spatial principal co-coordinates-redundancy analysis (SPCoA-RDA) was used to explore the influencing factors and mechanisms of CLUFCs.ResultsThe results show that there are obvious spatial heterogeneity and aggregation distribution characteristics of CLUFCs in Yancheng City. Through SPCoA-RDA, it is found that the spatial differentiation of CLUFCs is the result of the combination of internal (population density, road network, and water network) and external (spatial spillover effect) driving factors.DiscussionBased on these results, the study area was divided into eight types of cultivated land suitability zones under four aggregation relationships of CLUFCs. Comprehensively considering production, CLUFCs were evaluated by socio-economic and geo-spatial statistical dates, and strategies for guiding the coordinated development and sustainable management of urban cultivated land had been put forward. This study can provide a theoretical framework and certain feasible suggestions for the sustainable development and the transformation of cultivated land system in agriculture cities.

ABSTRACT Metagenomic next-generation sequencing (mNGS) has been a lack of method for pathogen quantitation. We explored the suitable concentration of T1 phage [internal control (IC)phage], Thermus thermophilus (ICT.T), and artificial DNA sequence (ICDNA) as mNGS ICs for pathogen quantitation and compared the quantitation efficiency among them. We prepared the simulated cerebrospinal fluid (CSF) samples composed of a pathogen cocktail, containing Staphylococcus aureus, Escherichia coli, Komagataella pastoris, and human cells to test the accuracy, linearity, and interference of IC quantitation. We also collected 15 clinical CSF conducting both mNGS and droplet digital PCR (ddPCR) to further verify the quantification efficacy of IC. In accuracy, the mNGS quantification of pathogen was more precise when the IC was 103 and 104 CFU/mL Thermus thermophilus or 103 and 104 PFU/mL T1 phage with the CV% of pathogens quantification most below 15%. The DNA sequence’ quantification was less accurate with all the CV% of pathogen quantitation above 15%. In linearity, compared to DNA sequence (all R 2 0.9). In interference, the mNGS quantification was affected obviously by human cell concentrations when the IC was DNA sequence (P < 0.0001), and the quantification was not interfered when the IC was the 103 CFU/mL Thermus thermophilus or 104 PFU/mL T1 phage. Furthermore, we revealed the mNGS quantitation was highly consistent with ddPCR in clinical CSF according to the linear regression (R 2 = 0.9646, P < 0.0001, k = 0.9362) and Bland-Altman (the bias of average difference is 4.033, with the 95% confidence interval from − 24.61 to 32.68). Thermus thermophilus and T1 phages are comparable as mNGS IC in pathogen quantitation and are both superior than artificial DNA sequences. In total, 1,000-CFU/mL Thermus thermophilus as mNGS IC may allow us to reflect directly the variation of pathogens in central nervous system infection patients. IMPORTANCE Metagenomic next-generation sequencing (mNGS) has been used broadly for pathogens detection of infectious diseases. However, there is a lack of method for the absolute quantitation of pathogens by mNGS. We compared the quantitative efficiency of three mNGS internal controls (ICs) Thermus thermophilus, T1 phages, and artificial DNA sequence and developed the most applicable strategies for pathogen quantitation via mNGS in central nervous system infection. The IC application strategy we developed will enable mNGS analysis to assess the pathogen load simultaneously with the detection of pathogens, which should provide critical information for quick decision-making of treatment as well as clinical prognosis.

Background: Omicron had swept the mainland China between December 2022 and January 2023, while SARS-CoV-2 still continued to evolve. To fully prepare for the next wave, it’s urgent to evaluate the humoral immune response post BA.5/BF.7 breakthrough infection against predominant sub-lineages among existing vaccination strategies and the elders. Method: This study enrolled a longitudinal young-adult cohort from 2/3-dose vaccination to 1 month after breakthrough infection, and an elder cohort at 1 month after breakthrough infection. Seral samples were collected and tested for humoral immune response to SARS-CoV-2 subvariants including WT, BA.2, BA.5, BF.7, BQ.1.1, CH.1.1, XBB.1.5. Results: BA.5/BF.7 breakthrough infection induced higher neutralization activity than solely vaccination in all SARS-CoV-2 strains, while the latest Omicron subvariants, BQ.1.1, CH.1.1, XBB.1.5, exhibited the strongest neutralization evasion ability. There was a negative correlation between age and humoral immune response in WT, BA.5, BQ.1.1, and XBB.1.5. Compared to non-vaccination groups, breakthrough infection in two-dose vaccination groups had significantly higher neutralizing antibody against WT, BA.2, BA.5, BF.7 but not to BQ.1.1, CH.1.1, XBB.1.5 while booster dose against the prototype prior-breakthrough would not further significantly enhance individual’s humoral responses against the latest Omicron subvariants. Conclusions: Newer variants manifest increasing immune evasion from neutralization and repeated prototype-based booster vaccines may not further enhance neutralizing antibody against emerging new variants. Older adults have lower levels of neutralizing antibody. Future vaccination strategies should aim to enhance effective neutralization to contemporary variants.

Long COVID hinders people from normal life and work, posing significant medical and economic challenges. Nevertheless, comprehensive studies assessing its impact on large populations in Asia are still lacking. We tracked over 20,000 patients infected with COVID-19 for the first time during the Omicron BA.2 outbreak in Shanghai from March-June 2022 for one year. Of the 21,799 COVID-19 patients who participated in the 6-month telephone follow-up, 1939 (8.89%) had self-reported long COVID symptoms. 450 long COVID patients participated in the 6-month outpatient follow-up. Participants underwent healthy physical examinations and questionnaires focused on long-COVID-related symptoms and mental health. Mobility problem (P

ABSTRACTOmicron and its sublineages are currently predominant and have triggered epidemiological waves of SARS-CoV-2 around the world due to their high transmissibility and strong immune escape ability. Vaccines are key measures to control the COVID-19 burden. Omicron BA.2 caused a large-scale outbreak in Shanghai since March 2022 and resulted in over 0.6 million laboratory-confirmed infections. The vaccine coverage of primary immunization among residents aged 3 years and older in Shanghai exceeded 90%, and inactivated COVID-19 vaccines were mainly delivered. In the context of high vaccine coverage, we conducted a cohort study to assess vaccine effects on reducing the probability of developing symptoms or severity of disease in infections or nonsevere cases. A total of 48,243 eligible participants were included in this study, the majority of whom had asymptomatic infections (31.0%) and mild-to-moderate illness (67.9%). Domestically developed COVID-19 vaccines provide limited protection to prevent asymptomatic infection from developing into mild-to-moderate illness and durable protection to prevent nonsevere illness from progressing to severe illness caused by Omicron BA.2. Partial vaccination fails to provide effective protection in any situation. The level of vaccine effects on disease progression in the elderly over 80 years old was relatively lower compared with other age groups. Our study results added robust evidence for the vaccine performance against Omicron infection and could improve vaccine confidence.

A wave of Omicron infections rapidly emerged in China in 2022, but large-scale data concerning the safety profile of vaccines and Coronavirus disease 2019 (COVID-19) infection features in liver transplant (LT) recipients have not been collected. Therefore, the aim of this study was to assess the protectiveness and safety profile of the inactivated vaccines in LT patients against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infections. A multi-centre retrospective study was conducted in a cohort with a history of liver transplantation. A total of 1881 participants (487 vaccinated and 1394 unvaccinated patients) were enrolled from seven centres in China. Fourteen of the participants were infected by Omicron, and 50% patients had over 14 days of viral shedding duration. The protection rate of COVID-19 vaccinations to Omicron was 2.59%. The three breakthrough infections occurred more than 6 months after fully vaccinated. A total of 96 (19.7%) vaccinated patients had adverse events, including fatigue, myalgia, liver dysfunction, swelling, and scleroma. There were more Grade 3 adverse events in the preoperative vaccination group than those in the postoperative vaccination group. Inactivated whole-virion SARS-CoV-2 vaccines are safe in patients with post-liver transplantation. The efficacy of inactivated vaccines decreases after 6 months of vaccination, it is recommended that liver transplant patients get boosted vaccinations as early as possible even when they are fully vaccinated. Although clinical manifestations of Omicron infections were mild in LT patients, unvaccinated patients might have a higher risk of liver dysfunction during infections.

The emerging new VOC B.1.1.529 (Omicron) variant has raised serious concerns due to multiple mutations, reported significant immune escape, and unprecedented rapid spreading speed. Currently, studies describing the neutralization ability of different homologous and heterologous booster vaccination against Omicron are still lacking. In this study, we explored the immunogenicity of COVID-19 breakthrough patients, BBIBP-CorV homologous booster group and BBIBP-CorV/ZF2001 heterologous booster group against SARS-CoV-2 pseudotypes corresponding to the prototype, Beta, Delta, and the emergent Omicron variant. Notably, at 14 days post two-dose inactivated vaccines, pVNT titre increased to 67.4 GMTs against prototype, 8.85 against Beta and 35.07 against Delta, while neutralization activity against Omicron was below the lower limit of quantitation in 80% of the samples. At day 14 post BBIBP-CorV homologous booster vaccination, GMTs of pVNT significantly increased to 285.6, 215.7, 250.8, 48.73 against prototype, Beta, Delta, and Omicron, while at day 14 post ZF2001 heterologous booster vaccination, GMTs of pVNT significantly increased to 1436.00, 789.6, 1501.00, 95.86, respectively. Post booster vaccination, 100% samples showed positive neutralization activity against Omicron, albeit illustrated a significant reduction (5.86- to 14.98-fold) of pVNT against Omicron compared to prototype at 14 days after the homologous or heterologous vaccine boosters. Overall, our study demonstrates that vaccine-induced immune protection might more likely be escaped by Omicron compared to prototypes and other VOCs. After two doses of inactivated whole-virion vaccines as the “priming” shot, a third heterologous protein subunit vaccine and a homologous inactivated vaccine booster could improve neutralization against Omicron.

Breakthrough infection of SARS-CoV-2 is a serious challenge, as increased infections were documented in fully-vaccinated individuals. Recipients with poor antibody response are highly vulnerable to reinfection, whereas those with strong antibody responses achieve sterilizing immunity. Thus far, biomarkers associated with levels of vaccine-elicited antibody response are still lacking. Here, we studied the antibody response of age- and gender-controlled healthy cohort, who received inactivated SARS-CoV-2 vaccines and profiled the B cell receptor repertoires in longitudinally consecutive samples. Upon vaccination, all vaccinated individuals displayed a convergent antibody response with shared common antibody clones and public neutralizing antibodies. Strikingly, poor vaccine-responders are distinguishable from strong vaccine-responders by a biased V-usage before vaccination and IgG to IgM mRNA ratio. These findings reveal molecular signatures associated with the different levels of vaccine-induced antibody response, which could be further developed into biomarkers for the design of vaccination strategies.

A COVID-19 booster vaccination is being comprehensively evaluated globally due to the emerging concern of reduced protection rate of previous vaccination and circulating Variants of Concern (VOC). But the safety and immunogenicity of homologous BBIBP-CorV boosting vaccination are yet to be thoroughly evaluated. We conducted this prospective, open-label study in Huashan Hospital using a third 6.5U BBIBP-CorV administered at an interval of 4–8 months following the previous two doses in healthy adults. Safety, anti-RBD response and neutralizing titers against SARS-CoV-2 and VOCs were examined. Sixty-three and forty participants entered the booster and the control group, respectively. A significant increase in IFN-γ SFU per million PBMCs was observed on day 14 against N peptide (20 vs. 5, P

Coronavirus disease 2019 (COVID-19) has caused more than 500 million infections and 6.2 million deaths globally, resulting in numerous sporting events being cancelled or postponed. Therefore, effective control strategies are urgently needed to prevent COVID-19 transmission at these local and global events. This article introduced the strategies utilized at the Tokyo and Beijing Olympics and proposed several measures for future reference.

Omicron variant of SARS-CoV-2 has become the predominant variant worldwide. VV116 is an oral drug with robust anti-SARS-CoV-2 efficacy in preclinical studies. We conducted an open, prospective cohort study to evaluate its safety and effectiveness in Chinese participants infected with the omicron variant from March 8th, 2022 to March 24th, 2022. 136 hospitalized nonsevere patients confirmed with COVID-19 were enrolled including 60 patients who received VV116 (300 mg, BID×5 days) in the treatment group and 76 patients who didn’t receive VV116 in the control group besides standard treatment. Viral load shedding time and adverse events were collected during the follow-up. There was no significant difference in baseline characteristics between the VV116 group and the control group, except for a higher symptom prevalence in the control group (P = 0.021). The median time from the first positive test to the first VV116 administration was 5 (range: 2-10) days. Participants who received VV116 within 5 days since the first positive test had a shorter viral shedding time than the control group (8.56 vs 11.13 days), and cox regression analysis showed adjusted HR of 2.37 [95%CI 1.50-3.75], P

The pathogenesis of liver in patients with hepatitis B virus-associated acute chronic liver failure (HBV-ACLF) remains largely unknown. We aimed to elucidate the molecular mechanism underlying the pathogenesis of liver in HBV-ACLF patients by using multiple approaches including transcriptome analysis. We performed transcriptomic sequencing analysis on the liver of HBV-ACLF patients (n = 6), chronic hepatitis B (n = 6), liver cirrhosis (n = 6) and normal control (n = 5), then explored the potential pathogenesis mechanism in liver specimen from another 48 subjects and further validated the molecular and cellular mechanisms using THP-1 cells. RNA-sequencing data analysis indicated that, among the genes up-regulated in HBV-ACLF, genes related to inflammatory response and chemotaxis accounted for a large proportion of the total DEGs. A number of key chemokines (CCL2, CCL5, CCL20, CXCL5, CXCL6, CXCL8) and NF-ĸB pathway were identified to be robust in the liver samples from HBV-ACLF patients. Interestingly, cylindromatosis (CYLD) was found to be downregulated in the liver of HBV-ACLF patients, in line with the well-established role of CYLD in regulating most of the chemokines and pro-inflammatory cytokines (CCL2, CCL5, CCL20, CXCL5, CXCL6, CXCL8, IL-6, IL-1β) via inhibition of NF-ĸB. Indeed, the knockdown of CYLD resulted in sustained activation of NF-ĸB in macrophages and enhanced chemokines and inflammatory cytokines production, which in turn enhanced chemotactic migration of neutrophil, monocyte, T lymphocytes, and NK cell. In conclusions, down-regulated CYLD aggravated inflammatory cell chemotaxis through enhancing NF-κB activation in HBV-ACLF patients, thereby participating in the pathogenesis of HBV-ACLF injury.

Shanghai has been experiencing the Omicron wave since March 2022. Though several studies have evaluated the risk factors of severe infections, the analyses of BA.2 infection risk and protective factors among geriatric people were much limited. This multicentre cohort study described clinical characteristics, and assessed risk and protective factors for geriatric Omicron severe infections. A total of 1377 patients older than 60 were enrolled, with 75.96% having comorbidities. The median viral shedding time and hospitalization time were nine and eight days, respectively. Severe and critical were associated with longer virus clearance time (aOR [95%CI]:0.706 (0.533–0.935), P = .015), while fully vaccinated/booster and paxlovid use shortened viral shedding time (1.229 [1.076–1.402], P = .002; 1.140 [0.019–1.274], P = .022, respectively). Older age (>80), cerebrovascular disease, and chronic kidney disease were risk factors of severe/critical. Fully vaccination was a significant protective factor against severe infections (0.237 [0.071–0.793], P = .019). We found patients with more than two comorbidities were more likely to get serious outcomes. These findings demonstrated that in the elderly older than 60 years old, older age (aged over 80), cerebrovascular disease, and chronic kidney disease were risk factors for severe infection. Patients with more than two comorbidities were more likely to get serious outcomes. Fully vaccinated/booster patients were less likely to be severe and vaccinations could shorten viral shedding time. The limitation of lacking an overall spectrum of COVID-19 infections among elders could be compensated in other larger-scale studies in the future.

To further describe the effect of the “fragile population” and their “higher-risk” comorbidities on prognosis among hospitalized Omicron patients, this observational cohort study enrolled hospitalized patients confirmed with SARS-CoV-2 during the 2022 Omicron wave in Shanghai, China. The primary outcome was progression to severe or critical cases. The secondary outcome was viral shedding time from the first positive SARS-CoV-2 detection. A total of 847 participants were enrolled, most of whom featured as advanced age (>70 years old: 30.34%), not fully vaccinated (55.84%), combined with at least 1 comorbidity (65.41%). Multivariate cox regression suggested age >70 years old (aHR[95%CI] 0.78[0.61–0.99]), chronic kidney disease (CKD) stage 4–5 (aHR[95%CI] 0.61[0.46–0.80]), heart conditions (aHR[95%CI] 0.76[0.60–0.97]) would elongate viral shedding time and fully/booster vaccination (aHR[95%CI] 1.4 [1.14–1.72]) would shorten this duration. Multivariate logistic regression suggested CKD stage 4–5 (aHR[95%CI] 3.21[1.45–7.27]), cancer (aHR[95%CI] 9.52[4.19–22.61]), and long-term bedridden status (aHR[95%CI] 4.94[2.36–10.44]) were the “higher” risk factor compared with the elderly, heart conditions, metabolic disorders, isolated hypertension, etc. for severity while female (aHR[95%CI] 0.34[0.16–0.68]) and fully/booster Vaccination (aHR[95%CI] 0.35[0.12–0.87]) could provide protection from illness progression. CKD stage 4–5, cancer and long-term bedridden history were “higher-risk” factors among hospitalized Omicron patients for severity progression while full vaccination could provide protection from illness progression.

Abstract SARS-CoV-2 vaccine booster dose can induce a robust humoral immune response, however, its cellular mechanisms remain elusive. Here, we investigated the durability of antibody responses and single-cell immune profiles following booster dose immunization, longitudinally over 6 months, in recipients of a homologous BBIBP-CorV/BBIBP-CorV or a heterologous BBIBP-CorV/ZF2001 regimen. The production of neutralizing antibodies was dramatically enhanced by both booster regimens, and the antibodies could last at least six months. The heterologous booster induced a faster and more robust plasmablast response, characterized by activation of plasma cells than the homologous booster. The response was attributed to recall of memory B cells and the de novo activation of B cells. Expanded B cell clones upon booster dose vaccination could persist for months, and their B cell receptors displayed accumulated mutations. The production of antibody was positively correlated with antigen presentation by conventional dendritic cells (cDCs), which provides support for B cell maturation through activation and development of follicular helper T (Tfh) cells. The proper activation of cDC/Tfh/B cells was likely fueled by active energy metabolism, and glutaminolysis might also play a general role in promoting humoral immunity. Our study unveils the cellular mechanisms of booster-induced memory/adaptive humoral immunity and suggests potential strategies to optimize vaccine efficacy and durability in future iterations.

BackgroundsDifferentiation between benign and malignant diseases in EBV-positive patients poses a significant challenge due to the lack of efficient diagnostic tools. Metagenomic Next-Generation Sequencing (mNGS) is commonly used to identify pathogens of patients with fevers of unknown-origin (FUO). Recent studies have extended the application of Next-Generation Sequencing (NGS) in identifying tumors in body fluids and cerebrospinal fluids. In light of these, we conducted this study to develop and apply metagenomic methods to validate their role in identifying EBV-associated malignant disease.MethodsWe enrolled 29 patients with positive EBV results in the cohort of FUO in the Department of Infectious Diseases of Huashan Hospital affiliated with Fudan University from 2018 to 2019. Upon enrollment, these patients were grouped for benign diseases, CAEBV, and malignant diseases according to their final diagnosis, and CNV analysis was retrospectively performed in 2022 using samples from 2018 to 2019.ResultsAmong the 29 patients. 16 of them were diagnosed with benign diseases, 3 patients were diagnosed with CAEBV and 10 patients were with malignant diseases. 29 blood samples from 29 patients were tested for mNGS. Among all 10 patients with malignant diagnosis, CNV analysis suggested neoplasms in 9 patients. Of all 19 patients with benign or CAEBV diagnosis, 2 patients showed abnormal CNV results. The sensitivity and specificity of CNV analysis for the identification for tumors were 90% and 89.5%, separately.ConclusionsThe application of mNGS could assist in the identification of microbial infection and malignancies in EBV-related diseases. Our results demonstrate that CNV detection through mNGS is faster compared to conventional oncology tests. Moreover, the convenient collection of peripheral blood samples adds to the advantages of this approach.

Tropheryma whipplei (TW) is the root cause of Whipple’s disease (WD), a rare infectious illness leading to multi-organ impairment. A prominent feature of WD is acute pneumonia, which can be exceedingly challenging to diagnose clinically due to the pathogen’s surreptitious nature. However and significantly, with the advent of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF), it offers clinicians a potent tool at their disposal to detect TW infections. The present study conducted a retrospective analysis of clinical data gleaned from five patients in Hunan Province in China. Findings in this study demonstrated the potential of BALF-mNGS in diagnosing pneumonia caused by TW infection.

Abstract Background Sepsis is still a major public health concern and a medical emergency due to its high morbidity and mortality. Accurate and timely etiology diagnosis is crucial for sepsis management. As an emerging rapid and sensitive pathogen detection tool, digital droplet PCR (ddPCR) has shown promising potential in rapid identification of pathogens and antimicrobial resistance genes. However, the diagnostic value and clinical impact of ddPCR tests remains to be studied in patients with suspected sepsis. PROGRESS trial is aimed to evaluate the clinical effectiveness of a novel ddPCR assay compared with standard practice. Methods PROGRESS is a multicenter, open-label, pragmatic randomized controlled trial (pRCT) set in ten hospitals, including departments of infectious disease and intensive care units. In this study, a total of 2292 patients with suspected sepsis will be randomly assigned to two arms: the ddPCR group and the control group with a ratio of 3:1. The primary outcome is the diagnostic efficacy, that is, the sensitivity and specificity of the ddPCR assay compared with the synchronous blood culture. Secondary outcomes include the mortality rates and the mean Sequential Organ Failure Assessment (SOFA) score at follow-up time points, the length of stay in the hospital, the time to directed antimicrobial therapy, duration of broad-spectrum antibiotic use, and the EQ-5D-5L score on day 90. Discussion It is the first multicenter pragmatic RCT to explore the diagnostic efficacy and clinical impact of the ddPCR assay in patients with suspected sepsis, taking advantage of both RCT’s ability to establish causality and the feasibility of pragmatic approaches in real-world studies (RWS). This trial will help us to get a comprehensive view of the assay’s capacity for precise diagnosis and treatment of sepsis. It has the potential to monitor the pathogen load change and to guide the antimicrobial therapy, making a beneficial impact on the prognosis of sepsis patients. Trial registration: ClinicalTrial.gov, NCT05190861. Registered January 13, 2022—‘Retrospectively registered’, https://clinicaltrials.gov/ct2/show/NCT05190861 .

Abstract Background The outbreak of SARS-CoV-2 at the end of 2019 sounded the alarm for early inspection on acute respiratory infection (ARI). However, diagnosis pathway of ARI has still not reached a consensus and its impact on prognosis needs to be further explored. Methods ESAR is a multicenter, open-label, randomized controlled, non-inferiority clinical trial on evaluating the diagnosis performance and its impact on prognosis of ARI between mNGS and multiplex PCR. Enrolled patients will be divided into two groups with a ratio of 1:1. Group I will be directly tested by mNGS. Group II will firstly receive multiplex PCR, then mNGS in patients with severe infection if multiplex PCR is negative or inconsistent with clinical manifestations. All patients will be followed up every 7 days for 28 days. The primary endpoint is time to initiate targeted treatment. Secondary endpoints include incidence of significant events (oxygen inhalation, mechanical ventilation, etc.), clinical remission rate, and hospitalization length. A total of 440 participants will be enrolled in both groups. Discussion ESAR compares the efficacy of different diagnostic strategies and their impact on treatment outcomes in ARI, which is of great significance to make precise diagnosis, balance clinical resources and demands, and ultimately optimize clinical diagnosis pathways and treatment strategies. Trial registration Clinicaltrial.gov, NCT04955756, Registered on July 9th 2021.

Abstract Background Encephalitis/meningitis brings a heavy disease burden, and the origin of disease remains unknown in 30–40% of patients. It is greatly significant that combinations of nucleic acid amplification and autoimmune antibody testing improves the diagnosis and treatment of encephalitis/meningitis. Moreover, though several diagnostic methods are in clinical use, a recognized and unified diagnosis and treatment process for encephalitis management remains unclear. Methods IMPROVE is a multicenter, open label, randomized controlled clinical trial that aims to evaluate the diagnostic performance, applications, and impact on patient outcomes of a new diagnostic algorithm that combines metagenomic next-generation sequencing (mNGS), multiplex polymerase chain reaction (PCR) and autoimmune antibody testing. The enrolled patients will be grouped into two parallel groups, multiplex PCR test plus autoimmune antibody group (Group I) or the mNGS plus autoimmune antibody group (Group II) with a patient ratio of 1:1. Both groups will be followed up for 12 months. The primary outcomes include the initial time of targeted treatment and the modified Rankin scale score on the 30th day of the trial. The secondary outcomes are the cerebrospinal fluid index remission rate on the 14th day, mortality rate on the 30th day, and an evaluation of diagnostic efficacy. The two groups are predicted to comprise of 484 people in total. Discussion To optimize the roadmap of encephalitis/meningitis, precise diagnosis, and treatment are of great significance. The effect of rapid diagnosis undoubtedly depends on the progression of new diagnostic tests, such as the new multiplex PCR, mNGS, and examination of broad-spectrum autoimmune encephalitis antibodies. This randomized-controlled study could allow us to obtain an accurate atlas of the precise diagnostic ability of these tests and their effect on the treatment and prognosis of patients. Trial registration ClinicalTrial.gov, NCT04946682. Registered 29 June 2021, ‘Retrospectively registered’, https://clinicaltrials.gov/ct2/show/NCT04946682?term=NCT04946682&draw=2&rank=1

ABSTRACT Accurate and timely etiological diagnosis is crucial for bloodstream infections (BSIs) due to their high disability and mortality. We conducted a single-center prospective cohort study to compare the digital droplet PCR (ddPCR) assay with traditional blood culture. A total of 169 blood samples from 122 patients with suspected BSIs were collected, mostly from the department of infectious diseases, the emergency department, and the intensive care units, and the clinical data were also recorded. Nucleic acid was extracted from the blood samples, and a 5-fluorescent-channel droplet digital PCR assay was performed and then fed back with the pathogen and its copies. In BSI patients, ddPCR reported an overall 85.71% (12/14) (95% confidence interval [CI], 56.15 to 97.48%) sensitivity, 100% (7/7) (95% CI, 56.09 to 100.00%) and 71.43% (5/7) (95% CI, 30.26 to 94.89%) sensitivity in patients without empirical treatment and in empirically treated patients, respectively. Compared to traditional blood culture, the overall detection rate of ddPCR was significantly higher, 11.27% (16/142) (95% CI, 6.78 to 17.93%) versus 30.28% (43/142) (95% CI, 23.01 to 38.64%), and the extra detection rate of ddPCR was 19.01% (27/142) (95% CI, 13.11 to 26.63%). Of the ddPCR-positive culture-negative cases, 74.19% (23/31) (95% CI, 55.07 to 87.46%) were consistent with the final clinical diagnosis, including 10 bacteria and fungi. The detection rate of ddPCR was significantly higher in patients with white blood cell (WBC) counts of >10 · 109/L, C-reactive protein (CRP) of >70 mg/L, or procalcitonin (PCT) of >0.9 ng/L. Pathogen loads detected by ddPCR are correlated with WBC, CRP, and especially, PCT levels, precisely and rapidly reflecting clinical disease progression. ddPCR has an important guiding value for the clinical use of antibiotics to achieve the best pathogen coverage and the antibacterial effect. Collectively, ddPCR showed a great diagnostic performance in BSIs and had an overall higher detection rate than blood culture. In addition, ddPCR could be used to dynamically monitor the disease progression and provide medication guidance on antibiotic use. IMPORTANCE ddPCR is a promising method to address the current challenges of BSI diagnosis and precise treatment, as it is highly efficient in DNA detection. It shortens the identification of BSI-related pathogens from several days of traditional bacterial culture to 4 to 5 h. It is extremely sensitive and more tolerant to PCR inhibitors, which may facilitate the amplification and enable the detection of a meager amount of DNA fragments in detecting BSI-related pathogens and drug-resistant genes. It can identify almost 20 pathogens in one reaction, which reduces the usage of clinical blood samples to no more than 2 mL. Additionally, dynamic monitoring, assessment of pathogens, and antibiotic resistance genes in patients could be used to guide timely and precise adjustment of antimicrobial prescription. The short turnaround time of ddPCR may have the potential to guide antimicrobial treatment in the very early stage of sepsis and reduce the mortality and disability rate of sepsis.

IntroductionDuring the coronavirus disease 2019 (COVID-19) pandemic, the early detection and isolation of individuals infected with severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) through mass testing can effectively prevent disease transmission. SARS-CoV-2 nucleic acid rapid detection based on loop-mediated isothermal amplification (LAMP) may be appropriate to include in testing procedures.MethodsWe used 860 nasopharyngeal specimens from healthcare workers of Huashan Hospital and COVID-19 patients collected from April 7th to 21st, 2022, to assess the clinical diagnostic performance of the LAMP assay marketed by Shanghai GeneSc Biotech and compared it to the result of a rapid antigen test (RAT) head-to-head.ResultsOverall, the diagnostic performance of LAMP assay and RAT were as follows. The LAMP assay represented higher sensitivity and specificity than RAT, especially in the extracted RNA samples. The sensitivity was 70.92% and 92.91% for direct LAMP and RNA-LAMP assay, respectively, while the specificity was 99.86% and 98.33%. The LAMP assay had overall better diagnostic performance on the specimens with relatively lower Ct values or collected in the early phase (≤7 days) of COVID-19. The combination of LAMP assay and RAT improved diagnostic efficiency, providing new strategies for rapidly detecting SARS-CoV-2.ConclusionThe LAMP assay are suitable for mass screenings of SARS-CoV-2 infections in the general population.

Improving the carbon sequestration capacity (CSC) of an ecosystem by optimizing urban ecological networks is one of the effective ways to achieve the goal of “carbon neutrality” in the world. The contradiction between the irreplaceable ecological function and economic development of Yancheng City is prominent. Therefore, taking Yancheng City as an example, this paper adopted the morphological spatial pattern analysis–minimum cumulative resistance (MSPA-MCR) model to establish the ecological network of Yancheng City in 2020 and combined it with complex network theory to evaluate its ecological base, network quality, and CSC. The results show that the ecological network of Yancheng City has obvious characteristics of coastal cities. There is a significant positive correlation between CSC and the clustering efficiency of ecological sources, and improving the clustering efficiency of vegetation and water ecological nodes is conducive to enhancing the CSC of ecological networks. In terms of functional restoration of ecological networks, four types of 13 ecological stepping stones and 12 ecological corridors have been designed to strengthen the connectivity and balance of the network, and the improvement of network robustness before and after optimization verifies that the optimization scheme is reasonable and effective. This study improved the optimization method of ecological networks in Yancheng City based on enhancing the CSC of ecological nodes, which provided a theoretical framework and practical reference for the realization of global strategic goals of carbon neutrality.

Since the construction of the 21st Century Maritime Silk Road, islands in China have undergone more rapid urbanization, commercialization, and tourism. The interactions between natural and anthropogenic processes, however, have severely disturbed island ecosystems. Therefore, it is crucial to understand these interactions and identify key areas for island ecosystem protection and restoration by assessing the spatiotemporal patterns of landscape ecological risk. In this study, we investigated the optimal spatial scale needed to analyze spatiotemporal changes in landscape ecological risk on Haitan Island from 2000 to 2020. The landscape index varied with the change in spatial size, and the optimal grid size and scale based on semivariogram analysis were 75 m and 500 × 500 m, respectively. The spatial patterns of land use and landscape ecological risk have significantly changed owing to urban development on Haitan Island, with large amounts of cropland and forest being replaced by impervious land. The overall threat level of landscape ecological risk has decreased, and lowest-risk areas have gradually become the dominant type in the region. However, the landscape fragmentation and degree of water loss is increasing, and the landscape ecological risk of offshore areas cannot be ignored. The spatial clustering characteristics of landscape ecological risk in each period were significant, and the hotspots in the spatial distribution of the landscape ecological risk index were mainly coastal areas. The impacts of human activities on regional landscape patterns and ecosystems are increasing in intensity, and population density and distance to urban centers are the main drivers. This study provides a theoretical reference for selecting an optimal scale of analysis for ecological risk assessment in island landscapes and can be used as a reference in island spatial regulation and environmental impact assessments.

Abstract A previously unknown beta coronavirus, SARS‐CoV‐2, was discovered from a cluster of patients with pneumonia of unknown cause in Wuhan since the end of 2019. Ever since the start of COVID‐19, government administrations, academic institutions, and technology enterprises are under unprecedented cooperation in controlling this outbreak from pathogen identification, epidemic situation assessment, to outbreak containment. Timely identification, isolation, and whole‐genome sequencing of SARS‐CoV‐2 have laid the foundation for effective control of this novel infection. With the increasing case numbers worldwide, more real‐time information is emerging, changing our understandings to SARS‐CoV‐2 outbreak, and nonetheless refining the outbreak control responses. The efficient management of COVID‐19 requires global collaboration and an efficient share of information.

ABSTRACTSerology detection is recognized for its sensitivity in convalescent patients with COVID-19, in comparison with nucleic acid amplification tests (NAATs). This article aimed to evaluate the diagnostic accuracy of serologic methods for COVID-19 based on assay design and post-symptom-onset intervals. Two authors independently searched PubMed, Cochrane library, Ovid, EBSCO for case–control, longitudinal and cohort studies that determined the diagnostic accuracy of serology tests in comparison with NAATs in COVID-19 cases and used QUADAS-2 for quality assessment. Pooled accuracy was analysed using INLA method. A total of 27 studies were included in this meta-analysis, with 4 cohort, 16 case–control and 7 longitudinal studies and 4565 participants. Serology tests had the lowest sensitivity at 0–7 days after symptom onset and the highest at >14 days. TAB had a better sensitivity than IgG or IgM only. Using combined nucleocapsid (N) and spike(S) protein had a better sensitivity compared to N or S protein only. Lateral flow immunoassay (LFIA) had a lower sensitivity than enzyme-linked immunoassay (ELISA) and chemiluminescent immunoassay (CLIA). Serology tests will play an important role in the clinical diagnosis for later stage COVID-19 patients. ELISA tests, detecting TAB or targeting combined N and S proteins had a higher diagnostic sensitivity compared to other methods.

ABSTRACTObjectives Severe or critical COVID-19 is associated with intensive care unit admission, increased secondary infection rate, and would lead to significant worsened prognosis. Risks and characteristics relating to secondary infections in severe COVID-19 have not been described. Methods Severe and critical COVID-19 patients from Shanghai were included. We collected lower respiratory, urine, catheters, and blood samples according to clinical necessity and culture and mNGS were performed. Clinical and laboratory data were archived. Results We found 57.89% (22/38) patients developed secondary infections. The patient receiving invasive mechanical ventilation or in critical state has a higher chance of secondary infections (P

Background To investigate the mortality and health care resource use among patients with severe or critical coronavirus disease of 2019 (COVID-19) in the first wave of pandemic in China. Methods We performed a systematic review and meta-analysis to investigate the mortality, discharge rate, length of hospital stay, and use of invasive ventilation in severe or critical COVID-19 cases in China. We searched electronic databases for studies from China with no restrictions on language or interventions patients received. We screened records, extracted data and assessed the quality of included studies in duplicate. We performed the meta-analysis using random-effect models through a Bayesian framework. Subgroup analyses were conducted to examine studies by disease severity, study location and patient enrolment start date. We also performed sensitivity analysis using various priors, and assessed between-study heterogeneity and publication bias for the primary outcomes. Results Out of 6,205 titles and abstracts screened, 500 were reviewed in full text. A total of 42 studies were included in the review, of which 95% were observational studies (n = 40). The pooled 28-day and 14-day mortalities among severe or critical patients were 20.48% (7,136 patients, 95% credible interval (CrI), 13.11 to 30.70) and 10.83% (95% CrI, 6.78 to 16.75), respectively. The mortality declined over time and was higher in patients with critical disease than severe cases (1,235 patients, 45.73%, 95% CrI, 22.79 to 73.52 vs. 3,969 patients, 14.90%, 95% CrI, 4.70 to 39.57) and patients in Hubei compared to those outside Hubei (6,719 patients, 26.62%, 95% CrI, 13.11 to 30.70 vs. 244 patients, 5.88%, 95% CrI 2.03 to 14.11). The length of hospital stay was estimated at 18.48 days (6,847 patients, 95% CrI, 17.59 to 21.21), the 28-day discharge rate was 50.48% (3,645 patients, 95% CrI, 26.47 to 79.53), and the use of invasive ventilation rate was 13.46% (4,108 patients, 95% CrI, 7.61 to 22.31). Conclusions Our systematic review and meta-analysis found high mortality among severe and critical COVID-19 cases. Severe or critical COVID-19 cases consumed a large amount of hospital resources during the outbreak.

Mangrove restoration is challenging within protected coastal habitats. Predicting the dominant species distributions in mangrove communities is essential for appropriate species selection and spatial planning for restoration. We explored the spatial distributions of six mangrove species, including their related environmental factors, thereby identifying potentially suitable habitats for mangrove protection and restoration. Based on six dominant mangrove species present in the Beibu Gulf, Guangxi, China, we used a linear correlation analysis to screen environmental factors. In addition, we used the maximum entropy model to analyze the spatial distributions of potential mangrove afforestation areas. Based on the spatial superposition analysis, we identified mangrove conservation and restoration hot spots. The findings indicate that topographic and bioclimatic factors affect the distribution of suitable mangrove habitats in the Beibu Gulf, followed by land use type, salinity, and substrate type. We identified 13,816 hm2 of prime mangrove habitat in the Beibu Gulf that is primarily distributed in protected areas. The protection rate for existing mangroves was 42.62%. According to the predicted spatial distributions of the mangrove plants, the findings suggest that mangrove restoration should be based on suitable species and site selection.

Background: Shotgun metagenomics has been used clinically for diagnosing infectious diseases. However, most technical assessments have been limited to individual sets of reference standards, experimental workflows, and laboratories. Methods: A reference panel and performance metrics were designed and used to examine the performance of shotgun metagenomics at 17 laboratories in a coordinated collaborative study. We comprehensively assessed the reliability, key performance determinants, reproducibility, and quantitative potential. Findings: Assay performance varied significantly across sites and microbial classes, with a read depth of 20 millions as a generally cost-efficient assay setting. Results of mapped reads by shotgun metagenomics could indicate relative and intra-site (but not absolute or inter-site) microbial abundance. Interpretation: Assay performance was significantly impacted by the microbial type, the host context, and read depth, which emphasizes the importance of these factors when designing reference reagents and benchmarking studies. Across sites, workflows and platforms, false positive reporting and considerable site/library effects were common challenges to the assay's accuracy and quantifiability. Our study also suggested that laboratory-developed shotgun metagenomics tests for pathogen detection should aim to detect microbes at 500 CFU/mL (or copies/mL) in a clinically relevant host context (10^5 human cells/mL) within a 24h turn-around time, and with an efficient read depth of 20M. Funding: This work was supported by National Science and Technology Major Project of China (2018ZX10102001).

Background: Metabolites are involved in biological process that govern the immune response to infection and vaccination. Knowledge of how metabolites interact with the immune system during immunization with the COVID-19 vaccine is limited. Here, we report that the serum metabolites are correlated with the magnitude of the antibody response in recipients receiving the inactivated COVID-19 vaccine, which provides critical information for studying metabolism regarding the human immune response to vaccination. Methods: 106 healthy volunteers without history of SARS-CoV-2 infection or vaccination were prospectively enrolled to receive the primary series of two doses of inactivated whole-virion SARS-CoV-2 vaccine. The serum samples were collected 2–4 weeks after the second dose. The magnitude of the anti-RBD antibody was quantified using surrogate virus neutralization tests. The profile of metabolites in serum was identified using untargeted metabolomics analysis. Results: The level of anti-RBD antibody 14–28 days after the second dose was significantly elevated and its interpersonal variability was diverse in a wide range. Thirty-two samples at extremes of the anti-RBD antibody titer were selected to discover the metabolic correlates. Two hundred and fifteen differential metabolites associated with antibody response independent of body mass index were identified. Pregnenolone and sphingolipid metabolism might be involved in the modulation of the human antibody response to the inactivated COVID-19 vaccine. Conclusion: We discovered key metabolites as well as those with a related functional significance that might modulate the human immune response to vaccination.

Background: High-speed urbanization has brought about a number of ecological and environmental problems, as well as the use of remote sensing to monitor the urban ecological environment and explore the main factors affecting its changes. It is important to promote the sustainable development of cities. Methods: In this study, we quantify the ecological quality of the study area from 2000 to 2020 based on the remote sensing ecological index (RSEI) and analyze its drivers through Geodetector and geographically weighted regression. Results: The RSEI of Fuzhou City from 2000 to 2020 showed an increasing followed by a decreasing trend, with obvious spatial autocorrelation. The main driving factors causing the spatial divergence of the RSEI were elevation (q = 0.48–0.63), slope (0.42–0.59), and GDP (0.3–0.42), and the driving effect and range of each factor changed with time. Conclusion: In this paper, we explore changes in the ecological environment in Fuzhou City over the past 20 years, as well as the scope and magnitude of the drivers, providing an important reference basis to improve the ecological environment quality of the city.

BackgroundDengue fever is a mosquito-borne febrile illness. Southeast Asia experienced severe dengue outbreaks in 2019, and over 1000 cases had been reported in Jiangxi, a previously known low-epidemic region in China. However, the emergence of a dengue virus epidemic in a non-epidemic region remains unclear.MethodsWe enrolled 154 dengue fever patients from four hospitals in Jiangxi, from April 2019 to September 2019. Real-time PCR, NS1 antigen rapid test, and IgM, IgG tests were performed, and 14 samples were outsourced to be sequenced metagenomically.ResultsAmong the 154 cases, 42 were identified as imported and most of them returned from Cambodia. A total of 113 blood samples were obtained and 106 were identified as DENV-1, two as DENV-2, and five were negative through RT-PCR. All DENV-1 strains sequenced in this study were all classified to one cluster and owned a high similarity with a Cambodia strain isolated in 2019. The evolutionary relationships of amino acid were consistent with that of nucleotide genome result. The sequence-based findings of Jiangxi strains were consistent with epidemiological investigation.ConclusionEpidemiological analysis demonstrated that the emergence of dengue cases led to autochthonous transmission in several cities in Jiangxi, a low-epidemic region before. This study emphasized future prevention and control of dengue fever in both epidemic and non-epidemic regions.

The urban heat island (UHI) phenomenon caused by rapid urbanization has become an important global ecological and environmental problem that cannot be ignored. In this study, the UHI effect was quantified using Landsat 8 image inversion land surface temperatures (LSTs). With the spatial scale of street units in Fuzhou City, China, using ordinary least squares (OLS) regression, geographically weighted regression (GWR) models, and multi-scale geographically weighted regression (MGWR), we explored the spatial heterogeneities of the influencing factors and LST. The results indicated that, compared with traditional OLS models, GWR improved the model fit by considering spatial heterogeneity, whereas MGWR outperformed OLS and GWR in terms of goodness of fit by considering the effects of different bandwidths on LST. Building density (BD), normalized difference impervious surface index (NDISI), and the sky view factor (SVF) were important influences on elevated LST, while building height (BH), forest land percentage (Forest_per), and waterbody percentage (Water_per) were negatively correlated with LST. In addition, built-up percentage (Built_per) and population density (Pop_Den) showed significant spatial non-stationary characteristics. These findings suggest the need to consider spatial heterogeneity in analyses of impact factors. This study can be used to provide guidance on mitigation strategies for UHIs in different regions.

The recent outbreak of human infections caused by SARS-CoV-2, the third zoonotic coronavirus has raised great public health concern globally. Rapid and accurate diagnosis of this novel pathogen posts great challenges not only clinically but also technologically. Metagenomic next-generation sequencing (mNGS) and reverse-transcription PCR (RT-PCR) have been the most commonly used molecular methodologies. However, each has their own limitations. In this study, we developed an isothermal, CRISPR-based diagnostic for COVID-19 with near single-copy sensitivity. The diagnostic performances of all three technology platforms were also compared. Our study aimed to provide more insights into the molecular detection of SARS-CoV-2, and also to present a novel diagnostic option for this new emerging virus.