Wuhan was the first epicentre of COVID-19 in the world, accounting for 80% of cases in China during the first wave. We aimed to assess household transmissibility of severe acute respiratory syndrome ...coronavirus 2 (SARS-CoV-2) and risk factors associated with infectivity and susceptibility to infection in Wuhan.
This retrospective cohort study included the households of all laboratory-confirmed or clinically confirmed COVID-19 cases and laboratory-confirmed asymptomatic SARS-CoV-2 infections identified by the Wuhan Center for Disease Control and Prevention between Dec 2, 2019, and April 18, 2020. We defined households as groups of family members and close relatives who did not necessarily live at the same address and considered households that shared common contacts as epidemiologically linked. We used a statistical transmission model to estimate household secondary attack rates and to quantify risk factors associated with infectivity and susceptibility to infection, accounting for individual-level exposure history. We assessed how intervention policies affected the household reproductive number, defined as the mean number of household contacts a case can infect.
27 101 households with 29 578 primary cases and 57 581 household contacts were identified. The secondary attack rate estimated with the transmission model was 15·6% (95% CI 15·2–16·0), assuming a mean incubation period of 5 days and a maximum infectious period of 22 days. Individuals aged 60 years or older were at a higher risk of infection with SARS-CoV-2 than all other age groups. Infants aged 0–1 years were significantly more likely to be infected than children aged 2–5 years (odds ratio OR 2·20, 95% CI 1·40–3·44) and children aged 6–12 years (1·53, 1·01–2·34). Given the same exposure time, children and adolescents younger than 20 years of age were more likely to infect others than were adults aged 60 years or older (1·58, 1·28–1·95). Asymptomatic individuals were much less likely to infect others than were symptomatic cases (0·21, 0·14–0·31). Symptomatic cases were more likely to infect others before symptom onset than after (1·42, 1·30–1·55). After mass isolation of cases, quarantine of household contacts, and restriction of movement policies were implemented, household reproductive numbers declined by 52% among primary cases (from 0·25 95% CI 0·24–0·26 to 0·12 0·10–0·13) and by 63% among secondary cases (from 0·17 0·16–0·18 to 0·063 0·057–0·070).
Within households, children and adolescents were less susceptible to SARS-CoV-2 infection but were more infectious than older individuals. Presymptomatic cases were more infectious and individuals with asymptomatic infection less infectious than symptomatic cases. These findings have implications for devising interventions for blocking household transmission of SARS-CoV-2, such as timely vaccination of eligible children once resources become available.
National Natural Science Foundation of China, Fundamental Research Funds for the Central Universities, US National Institutes of Health, and US National Science Foundation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell ...therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM).
This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m
. LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 10
cells/kg range, 0.07 to 2.1 × 10
) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group.
At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%). Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases. One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity. The overall response rate was 88% (95% confidence interval CI, 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response. Minimal residual disease was negative for 36/57 (63%) patients. The median time to response was 1 month (range, 0.4 to 3.5). At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable). Median overall survival for all patients was not reached.
LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM.
ClinicalTrials.gov , NCT03090659 ; Registered on March 27, 2017, retrospectively registered.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Fullerene‐based carbons are promising electrode materials for supercapacitors due to their unique carbon structures and tunable architectures at the molecular level. By introducing various functional ...groups with many elements on the fullerene cages, diverse in situ metal/nonmetal‐doped carbon materials with enhanced pseudocapacitances and/or double layer capacitances can be prepared. In the present work, a fullerene derivative, ferrocenylpyrrolidine C60, containing nitrogen and iron, is chosen as the only precursor. A unique microstructure is fabricated by a liquid–liquid interfacial precipitation process. Subsequently, a facile, one‐step annealing of the microstructure at different temperatures is performed. A series of in situ N and Fe‐codoped laminated 3D hierarchical carbon composites in the shape of a cross are successfully synthesized. The as‐prepared N and Fe‐codoped carbon material treated at 700 °C exhibits a high specific capacitance of 505.4 F g−1 at 0.1 A g−1. To the best knowledge, this is the highest supercapacitor capacitance based on fullerene electrode materials. The use of a fullerene derivative as an in‐situ doped carbon for applications in energy storage opens a new avenue for developing future synthetic strategies to extend the repertoire of electrode materials with high performance.
N and Fe‐codoped cross‐like 3D hierarchical carbon materials for high‐performance supercapacitors are successfully synthesized from an in‐situ doped fullerene, ferrocenylpyrrolidine C60 containing nitrogen and iron. The use of a fullerene derivative for applications in energy storage opens a new avenue for developing new synthetic strategies to extend the repertoire of electrode materials with remarkable performance.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Paeonia suffruticosa possesses various medicinal benefits and has been used extensively in traditional oriental medicine for thousands of years. Paeonol is the main component isolated from the root ...bark of Paeonia suffruticosa. The pharmacological effects of Paeonia suffruticosa are mostly attributed to paeonol. Paeonol injection has been successfully applied in China for nearly 50 years for inflammation/pain-related indications. Currently, the dosage forms of paeonol approved by China Food and Drug Administration include tablet, injection, and external preparations such as ointment and adhesive plaster. So far, the clinical applications of paeonol are mainly focusing on the anti-inflammatory activity. Studies of other pharmacological activities of paeonol are developing rapidly, and which may play an important role in the future. Besides, substantial mechanisms of pharmacological action of paeonol have been clarified in recent years. In this review, we summarize the pharmacological effects anti-inflammatory, neuroprotective, anti-tumor, anti-cardiovascular diseases and associated mechanisms of action of paeonol up to date.
•Pharmacological effects of paeonol are reviewed for the first time.•Pharmacological mechanisms of action of paeonol are reviewed up to date.•Paeonol derivatives are potentially attractive drugs worth to be studied further.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The Haber-Bosch process to produce ammonia for fertilizer currently relies on carbon-intensive steam reforming of methane as a hydrogen source. We present an electrochemical pathway in which ammonia ...is produced by electrolysis of air and steam in a molten hydroxide suspension of nano-Fe2O3. At 200°C in an electrolyte with a molar ratio of 0.5 NaOH/0.5 KOH, ammonia is produced at 1.2 volts (V) under 2 milliamperes per centimeter squared (mA cm–2) of applied current at coulombic efficiency of 35% (35% of the applied current results in the six-electron conversion of N2 and water to ammonia, and excess H2 is cogenerated with the ammonia). At 250°C and 25 bar of steam pressure, the electrolysis voltage necessary for 2 mA cm–2 current density decreased to 1.0 V.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Macroautophagy (hereafter called autophagy) is a highly conserved physiological process that degrades over-abundant or damaged organelles, large protein aggregates and invading pathogens via the ...lysosomal system (the vacuole in plants and yeast). Autophagy is generally induced by stress, such as oxygen-, energy- or amino acid-deprivation, irradiation, drugs,
. In addition to non-selective bulk degradation, autophagy also occurs in a selective manner, recycling specific organelles, such as mitochondria, peroxisomes, ribosomes, endoplasmic reticulum (ER), lysosomes, nuclei, proteasomes and lipid droplets (LDs). This capability makes selective autophagy a major process in maintaining cellular homeostasis. The dysfunction of selective autophagy is implicated in neurodegenerative diseases (NDDs), tumorigenesis, metabolic disorders, heart failure,
. Considering the importance of selective autophagy in cell biology, we systemically review the recent advances in our understanding of this process and its regulatory mechanisms. We emphasize the 'cargo-ligand-receptor' model in selective autophagy for specific organelles or cellular components in yeast and mammals, with a focus on mitophagy and ER-phagy, which are finely described as types of selective autophagy. Additionally, we highlight unanswered questions in the field, helping readers focus on the research blind spots that need to be broken.
China is one of the countries with the highest incidence of gastric cancer. There are differences in epidemiological characteristics, clinicopathological features, tumor biological characteristics, ...treatment patterns, and drug selection between gastric cancer patients from the Eastern and Western countries. Non‐Chinese guidelines cannot specifically reflect the diagnosis and treatment characteristics for the Chinese gastric cancer patients. The Chinese Society of Clinical Oncology (CSCO) arranged for a panel of senior experts specializing in all sub‐specialties of gastric cancer to compile, discuss, and revise the guidelines on the diagnosis and treatment of gastric cancer based on the findings of evidence‐based medicine in China and abroad. By referring to the opinions of industry experts, taking into account of regional differences, giving full consideration to the accessibility of diagnosis and treatment resources, these experts have conducted experts’ consensus judgement on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes. This guideline uses tables and is complemented by explanatory and descriptive notes covering the diagnosis, comprehensive treatment, and follow‐up visits for gastric cancer.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Understanding ecological niches of major tick species and prevalent tick-borne pathogens is crucial for efficient surveillance and control of tick-borne diseases. Here we provide an up-to-date review ...on the spatial distributions of ticks and tick-borne pathogens in China. We map at the county level 124 tick species, 103 tick-borne agents, and human cases infected with 29 species (subspecies) of tick-borne pathogens that were reported in China during 1950-2018. Haemaphysalis longicornis is found to harbor the highest variety of tick-borne agents, followed by Ixodes persulcatus, Dermacentor nutalli and Rhipicephalus microplus. Using a machine learning algorithm, we assess ecoclimatic and socioenvironmental drivers for the distributions of 19 predominant vector ticks and two tick-borne pathogens associated with the highest disease burden. The model-predicted suitable habitats for the 19 tick species are 14‒476% larger in size than the geographic areas where these species were detected, indicating severe under-detection. Tick species harboring pathogens of imminent threats to public health should be prioritized for more active field surveillance.
Herpes simplex virus type 1 (HSV-1) is the most common virus, with an estimated infection rate of 60⁻95% among the adult population. Once infected, HSV-1 can remain latent in the host for a lifetime ...and be reactivated in patients with a compromised immune system. Reactivation of latent HSV-1 can also be achieved by other stimuli. Though acyclovir (ACV) is a classic drug for HSV-1 infection, ACV-resistant strains have been found in immune-compromised patients and drug toxicity has also been commonly reported. Therefore, there is an urge to search for new anti-HSV-1 agents. Natural products with potential anti-HSV-1 activity have the advantages of minimal side effects, reduced toxicity, and they exert their effect by various mechanisms. This paper will not only provide a reference for the safe dose of these agents if they are to be used in humans, referring to the interrelated data obtained from in vitro experiments, but also introduce the main pharmacodynamic mechanisms of traditional Chinese medicine (TCM) against HSV-1. Taken together, TCM functions as a potential source for HSV-1 therapy by direct (blocking viral attachment/absorption/penetration/replication) or indirect (reducing the susceptibility to HSV-1 or regulating autophagy) antiviral activities. The potential of these active components in the development of anti-HSV-1 drugs will also be described.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Circadian rhythms of gene expression are generated by the combinatorial action of transcriptional and translational feedback loops as well as chromatin remodelling events. Recently, long noncoding ...RNAs (lncRNAs) that are natural antisense transcripts (NATs) to transcripts encoding central oscillator components were proposed as modulators of core clock function in mammals (Per) and fungi (frq/qrf). Although oscillating lncRNAs exist in plants, their functional characterization is at an initial stage.
By screening an Arabidopsis thaliana lncRNA custom-made array we identified CDF5 LONG NONCODING RNA (FLORE), a circadian-regulated lncRNA that is a NAT of CDF5. Quantitative real-time RT-PCR confirmed the circadian regulation of FLORE, whereas GUS- staining and flowering time evaluation were used to determine its biological function.
FLORE and CDF5 antiphasic expression reflects mutual inhibition in a similar way to frq/qrf. Moreover, whereas the CDF5 protein delays flowering by directly repressing FT transcription, FLORE promotes it by repressing several CDFs (CDF1, CDF3, CDF5) and increasing FT transcript levels, indicating both cis and trans function.
We propose that the CDF5/FLORE NAT pair constitutes an additional circadian regulatory module with conserved (mutual inhibition) and unique (function in trans) features, able to fine-tune its own circadian oscillation, and consequently, adjust the onset of flowering to favourable environmental conditions.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
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