Refining the phylogeny and taxonomy of the apple tribe Maleae (Rosaceae): insights from phylogenomic analyses of 563 plastomes and a taxonomic synopsis of Photinia and its allies in the Old World.

This study addresses the longstanding absence of a comprehensive phylogenetic backbone for the apple tribe Maleae, a deficiency attributed to limited taxon and marker sampling. We conducted an extensive taxon sampling, incorporating 563 plastomes from a diverse range of 370 species encompassing 26 presently recognized genera. Employing a range of phylogenetic inference methods, including RAxML and IQ-TREE2 for Maximum Likelihood (ML) analyses, we established a robust phylogenetic framework for the Maleae tribe. Our phylogenomic investigations provided compelling support for three major clades within Maleae. By integrating nuclear phylogenetic data with morphological and chromosomal evidence, we propose an updated infra-tribal taxonomic system, comprising subtribe Malinae Reveal, subtribe Lindleyinae Reveal, and subtribe Vauqueliniinae B.B.Liu (subtr. nov.). Plastid phylogenetic analysis also confirmed the monophyly of most genera, except for Amelanchier, Malus, Sorbus sensu lato, and Stranvaesia. In addition, we present a comprehensive taxonomic synopsis of Photinia and its morphological allies in the Old World, recognizing 27 species and ten varieties within Photinia, three species and two varieties within Stranvaesia, and two species and three varieties within Weniomeles. Furthermore, we also lectotypified 12 names and made two new combinations, Photiniamicrophylla (J.E.Vidal) B.B.Liu and Weniomelesatropurpurea (P.L.Chiu ex Z.H.Chen & X.F.Jin) B.B.Liu.

Photocatalytic Reduction of CO2 to HCOOH and CO by a Phosphine-Bipyridine-Phosphine Ir(III) Catalyst: Photophysics, Nonadiabatic Effects, Mechanism, and Selectivity.

Photocatalytic CO2 reduction is one of the best solutions to solve the global energy crisis and to realize carbon neutralization. The tetradentate phosphine-bipyridine (bpy)-phosphine (PNNP)-type Ir(III) photocatalyst, Mes-IrPCY2, was reported with a high HCOOH selectivity but the photocatalytic mechanism remains elusive. Herein, we employ electronic structure methods in combination with radiative, nonradiative, and electron transfer rate calculations, to explore the entire photocatalytic cycle to either HCOOH or CO, based on which a new mechanistic scenario is proposed. The catalytic reduction reaction starts from the generation of the precursor metal-to-ligand charge transfer (3 MLCT) state. Subsequently, the divergence happens from the 3 MLCT state, the single electron transfer (SET) and deprotonation process lead to the formation of one-electron-reduced species and Ir(I) species, which initiate the reduction reaction to HCOOH and CO, respectively. Interestingly, the efficient occurrence of proton or electron transfer reduces barriers of critical steps. In addition, nonadiabatic transitions play a nonnegligible role in the cycle. We suggest a lower free-energy barrier in the reaction-limiting step and the very efficient SET in 3 MLCT are cooperatively responsible for a high HCOOH selectivity. The gained mechanistic insights could help chemists to understand, regulate, and design photocatalytic CO2 reduction reaction of similar function-integrated molecular photocatalyst.

Nightmare or delight: Taxonomic circumscription meets reticulate evolution in the phylogenomic era.

Phylogenetic studies in the phylogenomics era have demonstrated that reticulate evolution greatly impedes the accuracy of phylogenetic inference, and consequently can obscure taxonomic treatments. However, the systematics community lacks a broadly applicable strategy for taxonomic delimitation in groups characterized by pervasive reticulate evolution. The red-fruit genus, Stranvaesia, provides an ideal model to examine the influence of reticulation on generic circumscription, particularly where hybridization and allopolyploidy dominate the evolutionary history. In this study, we conducted phylogenomic analyses integrating data from hundreds of single-copy nuclear (SCN) genes and plastomes, and interrogated nuclear paralogs to clarify the inter/intra-generic relationship of Stranvaesia and its allies in the framework of Maleae. Analyses of phylogenomic discord and phylogenetic networks showed that allopolyploidization and introgression promoted the origin and diversification of the Stranvaesia clade, a conclusion further bolstered by cytonuclear and gene tree discordance. With a well-inferred phylogenetic backbone, we propose an updated generic delimitation of Stranvaesia and introduce a new genus, Weniomeles. This new genus is distinguished by its purple-black fruits, thorns trunk and/or branches, and a distinctive fruit core anatomy characterized by multilocular separated by a layer of sclereids and a cluster of sclereids at the top of the locules. Through this study, we highlight a broadly-applicable workflow that underscores the significance of reticulate evolution analyses in shaping taxonomic revisions from phylogenomic data.

Malus includes Docynia (Maleae, Rosaceae): evidence from phylogenomics and morphology.

Docynia has been treated as a separate genus or merged into Cydonia or Docyniopsis. Our phylogenomic evidence from 797 single-copy nuclear genes and plastomes confirmed the sister relationship between Docynia and Docyniopsis. By integrating the phylogenomic and morphological evidence, we propose to accept a broad generic concept of Malus and merge Docynia into Malus. Three new combinations are also made here: Malusdelavayi (Franch.) B.B.Liu, M.indica (Wall.) B.B.Liu and M.longiunguis (Q.Luo & J.L.Liu) B.B.Liu.

Water-Stable Hybrid Lead-Free Perovskite for Negative Temperature Coefficient Thermistors.

Negative temperature coefficient (NTC) thermistors feature higher sensitivities and faster response speeds and thereby have particular applications in many fields. However, current NTC thermistors are mostly based on inorganic ceramic materials, which show obvious drawbacks in material synthesis, property modulation, and flexible film fabrication. Herein, we report, for the first time, the promising application of an inorganic-organic hybrid NTC thermistor. A new lead-free hybrid iodo bismuthate [1,1',1″-(benzene-1,3,5-triyl)tris(3-methyl-1H-imidazol-3-ium)]Bi2I9 [denoted as (Me3TMP)Bi2I9] was synthesized by a "double-free" strategy. (Me3TMP)Bi2I9 features a lead-free binuclear bismuth iodine anion charge compensated by a "classic hydrogen-bond-free" cation. (Me3TMP)Bi2I9 exhibits remarkable stability in water and UV light irradiation and shows the largest temperature sensitivity coefficient among all reported NTC materials. Theoretical calculation and detailed structural analysis disclose that the seriously distorted (BiI6) octahedra are responsible for the intriguing NTC effect for (Me3TMP)Bi2I9.

Burden, Trends, and Inequality of Dental Caries in the U.S., 1990-2019.

INTRODUCTION: Over the past 2 decades in the U.S., the reduced burden and narrowed inequality in oral health among children are in stark contrast with the high burden and widening inequality in adult oral health. This study aimed to explore the burden, trends, and inequalities of untreated caries in permanent teeth in the U.S. during 1990-2019. METHODS: Data on burden of untreated caries in permanent teeth were extracted from the Global Burden of Disease Study 2019. A set of advanced analytical methods were applied to provide an in-depth characterization of the epidemiologic profile of dental caries in the U.S. Analyses were conducted during April 2022-October 2022. RESULTS: In 2019, age-standardized incidence and prevalence of untreated caries in permanent teeth were respectively 39,111.7 (95% uncertainty interval=35,073.0-42,964.9) and 21,722.5 (95% uncertainty interval=18,748.7-25,090.3) per 100,000 person-years. Population growth was the primary driver of the increased caries cases, which contributed 31.3% and 31.0% of the increase in the number of incident and prevalent caries cases, respectively, during 1990-2019. The highest caries burden was noted in Arizona, West Virginia, Michigan, and Pennsylvania. The slope index of inequality remained stable (p=0.076), whereas the relative index of inequality increased significantly (average annual percent change=0.04, p<0.001) in the U.S. The burden of untreated caries in permanent teeth remained significant with a widening cross-state inequality during 1990-2019. CONCLUSIONS: The oral healthcare system in the U.S. needs to prioritize health promotion and prevention with a focus on expanding access, affordability, and equity.

Thermally activated delayed fluorescence of a Ir(III) complex: absorption and emission properties, nonradiative rates, and mechanism.

One recent experimental study reported a Ir(III) complex with thermally activated delayed fluorescence (TADF) phenomenon in solution, but its luminescent mechanism is elusive. In this work, we combined density functional theory (DFT), time-dependent DFT (TDDFT) and multi-state complete active space second-order perturbation theory (MS-CASPT2) methods to investigate excited-state properties, photophysics, and emission mechanism of this Ir(III) complex. Two main absorption bands observed in experiments can be attributed to the electronic transition from the S0 state to the S1 and S2 states; while, the fluorescence and phosphorescence are generated from the S1 and T1 states, respectively. Both the S1 and T1 states have clear metal-to-ligand charge transfer (MLCT) character. The present computational results reveal a three-state model including the S0, S1 and T1 states to rationalize the TADF behavior. The small energy gap between the S1 and T1 states benefits the forward and reverse intersystem crossing (ISC and rISC) processes. At 300 K, the rISC rate is five orders of magnitude larger than the phosphorescence rate therefore enabling TADF. At 77 K, the rISC rate is sharply decreased but remains close to the phosphorescence rate; therefore, in addition to the phosphorescence, the delayed fluorescence could also contribute to the experimental emission. The estimated TADF lifetime agrees well with experiments, 9.80 vs. 6.67 µs, which further verifies this three-state model.

Metabolic Disease Management Guideline for National Metabolic Management Center(2nd edition) / 中华内分泌代谢杂志

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Small-molecule anti-COVID-19 drugs and a focus on China's homegrown mindeudesivir (VV116) / 医学前沿

The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection. So far, a few small-molecule antiviral drugs, including nirmatrelvir-ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19. Nirmatrelvir-ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19. However, the existing treatment options have limitations, and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed. To date, four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China. These drugs include azvudine, simnotrelvir-ritonavir (Xiannuoxin), leritrelvir, and mindeudesivir (VV116). Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression. In this review, we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19. These findings will expand our understanding and highlight the potential widespread application of China's homegrown anti-COVID-19 drugs.

Dissecting Causal Relationships Between Gut Microbiota, Blood Metabolites, and Stroke: A Mendelian Randomization Study / 대한뇌졸중학회지

Background@#and Purpose We investigated the causal relationships between the gut microbiota (GM), stroke, and potential metabolite mediators using Mendelian randomization (MR). @*Methods@#We leveraged the summary statistics of GM (n=18,340 in the MiBioGen consortium), blood metabolites (n=115,078 in the UK Biobank), and stroke (cases n=60,176 and controls n=1,310,725 in the Global Biobank Meta-Analysis Initiative) from the largest genome-wide association studies to date. We performed bidirectional MR analyses to explore the causal relationships between the GM and stroke, and two mediation analyses, two-step MR and multivariable MR, to discover potential mediating metabolites. @*Results@#Ten taxa were causally associated with stroke, and stroke led to changes in 27 taxa. In the two-step MR, Bifidobacteriales order, Bifidobacteriaceae family, Desulfovibrio genus, apolipoprotein A1 (ApoA1), phospholipids in high-density lipoprotein (HDL_PL), and the ratio of apolipoprotein B to ApoA1 (ApoB/ApoA1) were causally associated with stroke (all P<0.044). The causal associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were validated using the weighted median method in an independent cohort. The three GM taxa were all positively associated with ApoA1 and HDL_PL, whereas Desulfovibrio genus was negatively associated with ApoB/ApoA1 (all P<0.010). Additionally, the causal associations between the three GM taxa and ApoA1 remained significant after correcting for the false discovery rate (all q-values <0.027). Multivariable MR showed that the associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were mediated by ApoA1 and HDL_PL, each accounting for 6.5% (P=0.028) and 4.6% (P=0.033); the association between Desulfovibrio genus and stroke was mediated by ApoA1, HDL_PL, and ApoB/ApoA1, with mediated proportions of 7.6% (P=0.019), 4.2% (P=0.035), and 9.1% (P=0.013), respectively. @*Conclusion@#The current MR study provides evidence supporting the causal relationships between several specific GM taxa and stroke and potential mediating metabolites.

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Methylglyoxal (MG) is a novel signaling molecule with multiple functions in plants. To explore the effects of MG on Chinese chestnut (Castanea mollissima) under drought stress, two-year-old 'Huangpeng' chestnut seedlings were treated with 15% polyethylene glycol (PEG) coupled with MG or its scavenger N-acetyl-L-cys-teine (NAC). We measured the activities of antioxidant enzymes, including superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR), and glyoxalase enzymes, including glyoxalase Ⅰ (GlyⅠ) and glyoxalase Ⅱ(GlyⅡ). Contents of antioxidants such as endogenous MG, malondialdehyde (MDA), H2O2, and O2-· as well as the osmotic adjustment substances including proline (Pro), soluble sugar (SS), glycine betaine (GB) were also detected. The results showed that 0.5 mmol·L-1 MG significantly increased the activities of antioxidant enzymes (SOD, POD, CAT, APX, GR) and glyoxalase enzymes (GlyⅠ, GlyⅡ) in leaves of chestnut seedlings under drought stress, elevated the contents of osmotic adjustment substances (Pro, SS, GB) and antioxidant substances (ASA, GSH), and reduced the contents of MG, MDA, H2O2, O2-· and dehydroascorbate (DHA). Drought stress induced damages such as membrane lipid peroxidation and osmotic stress was alleviated by MG, leading to an overall improved adaptability of chestnut to drought stress. Moreover, the addition of MG scavenger NAC could reverse the effects induced by MG, indicating that MG had positive impacts on drought resistance of chestnut plants. Our study provided a theoretical basis for further exploring the mechanism of MG in alleviating drought stress induced symptoms in chestnut.

Ultrathin covalent and cuprophilic interaction-assembled copper-sulfur monolayer in organic metal chalcogenide for oriented photoconductivity.

We report the thinnest copper sulfur atomic monolayer in an organic copper chalcogenide [Cu(CMP)]n (CMP = 5-chloro-2-mercaptopyridine). The layer features a new type of copper sulfur structure woven by both covalent bond and cuprophilic interaction and shows an intriguing oriented photoconductivity.

Association between the Neutrophil-to-lymphocyte Ratio and New-onset Subclinical Macrovascular and Microvascular Diseases in the Chinese Population / 生物医学与环境科学（英文）

OBJECTIVE@#The association between neutrophil-to-lymphocyte ratio (NLR) with subclinical macrovascular and microvascular diseases has been less investigated. We sought to examine the association between NLR and new-onset subclinical macrovascular and microvascular abnormalities in the Chinese population.@*METHODS@#From a community cohort, we included 6,430 adults aged ≥ 40 years without subclinical macrovascular and microvascular diseases at baseline. We measured subclinical macrovascular and microvascular abnormalities separately using the ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), and albuminuria.@*RESULTS@#During a mean follow-up of 4.3 years, 110 participants developed incident abnormal ABI, 746 participants developed incident elevated baPWV, and 503 participants developed incident albuminuria. Poisson regression analysis indicated that NLR was significantly associated with an increased risk of new-onset abnormal ABI, elevated baPWV, and albuminuria. Compared to overweight/obese participants, we found a much stronger association between NLR and subclinical vascular abnormalities in participants with normal weight. Furthermore, we found an interaction between the NLR and body mass index (BMI) on the risk of new-onset abnormal ABI ( P for interaction: 0.01).@*CONCLUSION@#NLR was associated with subclinical macrovascular and microvascular diseases in the Chinese population. Furthermore, in participants with normal weight, the association between NLR and subclinical vascular abnormalities was much stronger.

Comprehensive metabolite profile of multi-bioactive extract from tree peony (Paeonia ostii and Paeonia rockii) fruits based on MS/MS molecular networking.

Tree peony seed, traditionally used for edible oil production, is rich in α-linolenic acid. However, little attention is given to the fruit by-products during seed oil production. The present work aimed to comprehensively investigate the phytochemical constituents and multiple biological activities of different parts of tree peony fruits harvested from Paeonia ostii and Paeonia rockii. 130 metabolites were rapidly identified through UPLC-Triple-TOF-MS on the basis of MS/MS molecular networking. Metabolite quantification was performed through the targeted approach of HPLC-ESI-QQQ-MS. Eight chemical markers were screened via principal component analysis (PCA) for distinguishing species and tissues. Interestingly, two dominant compounds, paeoniflorin and trans-resveratrol, are specially localized in seed kernel and seed coat, respectively. Unexpectedly, the extracts of fruit pod and seed coat showed significantly stronger antioxidant, antibacterial, and anti-neuroinflammatory activities than seed kernel from both P. ostii and P. rockii. Our work demonstrated that tree peony fruit is promising natural source of bioactive components and provided its potential utilization in food and pharmaceutical industries.

Association of Visit-to-Visit Variabilities in Metabolic Factors with Chronic Kidney Disease in Chinese Adults Living in Shanghai / 生物医学与环境科学（英文）

Objective@#This study aimed to examine the association of visit-to-visit variabilities in metabolic factors with chronic kidney disease (CKD) in Shanghai community residents.@*Methods@#We used data from a cohort study of community residents who participated in three examinations in 2008, 2009, and 2013, respectively. Fasting plasma glucose (FPG) level, blood pressure (BP), and lipid levels were determined in 2,109 participants at all three visits, and CKD was evaluated between the second and the third visits. Visit-to-visit variabilities in metabolic factors were described by coefficients of variation (CV) at three visits. A variability score was calculated by adding the numbers of metabolic factors with a high variability defined as the highest quartile of CV. CKD was defined as the estimated glomerular filtration rate < 60 mL/min per 1.73 m @*Results@#A total of 200 (9.5%) participants had CKD at the third visit. Compared with the lowest quartile of CV, the highest quartile was associated with a 70% increased risk of CKD for FPG [odds ratio, @*Conclusion@#The visit-to-visit variabilities in metabolic factors were significantly associated with the risks of CKD in Shanghai community residents.

Inverted U-Shaped Associations between Glycemic Indices and Serum Uric Acid Levels in the General Chinese Population: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study / 生物医学与环境科学（英文）

Objective@#The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population.@*Methods@#The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models.@*Results@#A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices).@*Conclusion@#An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.

The complete chloroplast genome sequence of Magnolia mexicana DC. (Magnoliaceae) from Central America.

The chloroplast genome of the Magnolia species from Central America has never been reported. With its local use for food flavoring, medicine, and wood, M. mexicana has been of good economic importance. In the present study, the complete chloroplast genome of M. mexicana was assembled via the genome skimming data. As a typical quadripartite structure, the plastome of M. mexicana with 159,906 bp in length includes two inverted repeats (26,554 bp) separated by a small single copy region (18,761 bp) as well as a large single copy region (88,037 bp). This chloroplast genome consists of 131 different genes, including 86 protein coding genes (CDS), eight rRNA genes, and 37 tRNA genes. The maximum likelihood phylogenetic analysis showed that M. mexicana from Central America was closely related to an evergreen species, M. odoratissima from East Asia.

Design, Synthesis, and Photocatalytic Application of Moisture-Stable Hybrid Lead-Free Perovskite.

The employment of hybrid perovskite MAPbX3 (MA = CH3NH3+, X = Br or I) as photocatalysts in a photocatalytic hydrogen evolution reaction represents a promising approach to store solar energy. However, the toxicity of Pb makes these materials difficult to pass environmental evaluation while the intrinsic moisture sensitivity puts forward high anhydrous requirements in photocatalysts synthesis, storage, and application, which further reduces their service life. Herein, we demonstrate a hydrogen-bond-free strategy to synthesize moisture-stable hypotoxic hybrid perovskite for photocatalytic application by replacing traditional protonated countercations with alkylated countercations in a Pb-free hybrid system, which prevents water eroding hybrid perovskites via strong hydrogen bonds. A zero-dimensional Bi-based perovskite (3-ethylbenzo[d]thiazol-3-ium)4Bi2I10 (EtbtBi2I10) was synthesized, which contains dimeric (Bi2I10)4- formed by edge-sharing (BiI6) octahedra being different from the binuclear cluster in widely studied MA3Bi2I9. Theoretical calculations indicate that the electron communication between inorganic and organic moieties is responsible for its broadband absorption with a narrow band gap of 2.04 eV. EtbtBi2I10 exhibits excellent stability in distilled water, moisture air, acid solution, and UV-light irradiation. It shows effective photocatalytic performance in HI splitting to generate hydrogen with the performance comparable with MAPbI3. Introducing electron and hole-transporting channels drastically enhances the photocatalytic reaction.

Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial

ObjectivesTo assess the efficacy and safety of hydroxychloroquine (HCQ) plus standard-of-care (SOC) compared with SOC alone in adult patients with COVID-19. DesignMulticenter, open-label, randomized controlled trial. Setting16 government-designated COVID-19 treatment centers in China through 11 to 29 in February 2020. Participants150 patients hospitalized with laboratory confirmed COVID-19 were included in the intention to treat analysis. 75 patients were assigned to HCQ plus SOC and 75 to SOC alone. InterventionsHCQ was administrated with a loading dose of 1, 200 mg daily for three days followed by a maintained dose of 800 mg daily for the remaining days (total treatment duration: 2 or 3 weeks for mild/moderate or severe patients, respectively). Main outcome measuresThe primary outcome was whether participants had a negative conversion of SARS-CoV-2 by 28 days, and was analyzed according to the intention-to-treat principle. Adverse events were analyzed in the safety population in which HCQ recipients were participants who actually received at least one dose of HCQ and HCQ non-recipients were those actually managed with SOC alone. ResultsAmong 150 patients, 148 were with mild to moderate disease and 2 were with severe disease. The mean days ({+/-} standard deviation, min to max) from symptoms onset to randomization was 16.6 ({+/-}10.5 days, 3 to 41 days). The negative conversion probability by 28 days in SOC plus HCQ group was 85.4% (95% confidence interval (CI) 73.8% to 93.8%), similar to that in the SOC group 81.3% (95%CI 71.2% to 89.6%). Between-group difference was 4.1% (95%CI -10.3% to 18.5%). In the safety population, adverse events were recorded in 7 (8.8%) HCQ non-recipients (N=80) and in 21 (30%) HCQ recipients (N=70). The most common adverse event in the HCQ recipients was diarrhea, reported in 7 (10%) patients. Two HCQ recipients reported serious adverse events. ConclusionsThe administration of HCQ did not result in a significantly higher negative conversion probability than SOC alone in patients mainly hospitalized with persistent mild to moderate COVID-19. Adverse events were higher in HCQ recipients than in HCQ non-recipients. Trial registrationChiCTR2000029868 What is already known on this topic-- The pandemic of coronavirus disease 2019 (COVID-19) imposes substantial burdens on individuals, communities, health-care facilities, markets, governments, etc. globally. -- There is no specific treatment approved for COVID-19 or vaccine to prevent infection with the novel coronavirus. -- During the urgent pandemic, media headlines the utility of drugs without solid evidence but buries the side-effects of these drugs. What this study adds-- In this randomized clinical trial of patients mainly with persistent mild to moderate COVID-19, exposure to hydroxychloroquine led to a similar probability of virus elimination comparing to the current standard-of-care. -- Adverse events, mostly gastrointestinal related, were significantly increased in patients who received hydroxychloroquine. -- Overall, the results from our trial do not support the use of hydroxychloroquine in patients with persistent mild to moderate COVID-19. Print abstractO_ST_ABSStudy questionC_ST_ABSTo assess the efficacy and safety of hydroxychloroquine (HCQ) plus standard-of-care (SOC) compared with SOC alone in adult patients with COVID-19. MethodsThis is a multicenter, open-label, randomized controlled trial conducted in 16 government-designated COVID-19 treatment centers in China through 11 to 29 in February 2020. A total of 150 patients hospitalized with laboratory confirmed COVID-19 were included in the intention to treat analysis. Among them, 75 patients were assigned to HCQ plus SOC and 75 to SOC alone. HCQ was administrated with a loading dose of 1, 200 mg daily for three days followed by a maintained dose of 800 mg daily for the remaining days (total treatment duration: 2 or 3 weeks for mild/moderate or severe patients, respectively). The primary outcome was whether participants had a negative conversion of SARS-CoV-2 by 28 days, and was analyzed according to the intention to treat principle. Adverse events were analyzed in the safety population in which HCQ recipients were participants who actually received at least one dose of HCQ and HCQ non-recipients were those actually managed with SOC alone. Study answer and limitationsAmong 150 patients, 148 were with mild to moderate disease and 2 were with severe disease. The mean days ({+/-} standard deviation, min to max) from symptoms onset to randomization was 16.6 ({+/-}10.5 days, 3 to 41 days). The negative conversion probability by 28 days in SOC plus HCQ group was 85.4% (95% confidence interval (CI) 73.8% to 93.8%), similar to that in the SOC group 81.3% (95%CI 71.2% to 89.6%). Between-group difference was 4.1% (95%CI -10.3% to 18.5%). In the safety population, adverse events were recorded in 7 (8.8%) HCQ non-recipients (N=80) and in 21 (30%) HCQ recipients (N=70) with two serious adverse events. The most common adverse event in the HCQ recipients was diarrhea, reported in 7 (10%) patients. Two HCQ recipients reported serious adverse events. What this study addsOur trial does not support the use of hydroxychloroquine in patients with persistent mild to moderate COVID-19 due to limited effects on virus eliminating and significantly increased adverse events. Funding, competing interests, data sharingThis work was supported by the Emergent Projects of National Science and Technology (2020YFC0844500), National Natural Science Foundation of China (81970020, 81770025), National Key Research and Development Program of China (2016YFC0901104), Shanghai Municipal Key Clinical Specialty (shslczdzk02202, shslczdzk01103), National Innovative Research Team of High-level Local Universities in Shanghai, Shanghai Key Discipline for Respiratory Diseases (2017ZZ02014), National Major Scientific and Technological Special Project for Significant New Drugs Development (2017ZX09304007), Key Projects in the National Science and Technology Pillar Program during the Thirteenth Five-year Plan Period (2018ZX09206005-004, 2017ZX10202202-005-004, 2017ZX10203201-008). All authors declared no competing interests. Anonymized datasets can be made available on reasonable request after approval from the trial management committee. Study registrationChiCTR2000029868

Typification of 23 names in Eriobotrya (Maleae, Rosaceae).

As part of a comprehensive systematic study on the genus Eriobotrya and its close relatives from the E & SE Asia, new typifications of 23 names are presented here, along with some nomenclatural notes of the names involved. We lectotypified 22 names including accepted names and synonyms. They are: E. acuminatissima, E. bengalensis var. angustifolia; E. bengalensis f. intermedia, E. brackloi, E. brackloi var. atrichophylla, E. elliptica var. petelotii, E. fragrans var. furfuracea, E. glabrescens, E. grandiflora, E. henryi, E. oblongifolia, E. petiolata, E. platyphylla, E. poilanei, E. prinoides, E. prinoides var. laotica, E. salwinensis, E. serrata, E. stipularis, Hiptage cavaleriei, Photinia longifolia, Symplocos seguinii. One neotype of Photinia dubia was also proposed in this study, and E. pseudoraphiolepis and Mespilus cuila were identified as superfluous names. In addition, we also summarized the typification of 18 names for taxonomic reference: E. angustissima, E. balgooyi, E. condaoensis, E. × daduheensis, E. elliptica, E. fulvicoma, E. fragrans, E. glabrescens var. victoriensis, E. hookeriana, E. latifolia, E. obovata, E. malipoensis, E. merguiensis, E. tengyuehensis, E. wardii, Mespilus bengalensis, Photinia deflexa, and M. japonica.