Molecular mechanisms underlying the signal perception and transduction during seed germination.

QuerySeed germination is a vital step in the life cycle of a plant, playing a significant role in seedling establishment and crop yield potential. It is also an important factor in the conservation of plant germplasm resources. This complex process is influenced by a myriad of factors, including environmental conditions, the genetic makeup of the seed, and endogenous hormones. The perception of these environmental signals triggers a cascade of intricate signal transduction events that determine whether a seed germinates or remains dormant. Despite considerable progress in uncovering the molecular mechanisms governing these processes, many questions remain unanswered. In this review, we summarize the current progress in the molecular mechanisms underlying the perception of environmental signals and consequent signal transduction during seed germination, and discuss questions that need to be addressed to better understand the process of seed germination and develop novel strategies for germplasm improvement.

Orthogonal Subspace Representation for Generative Adversarial Networks.

Disentanglement learning aims to separate explanatory factors of variation so that different attributes of the data can be well characterized and isolated, which promotes efficient inference for downstream tasks. Mainstream disentanglement approaches based on generative adversarial networks (GANs) learn interpretable data representation. However, most typical GAN-based works lack the discussion of the latent subspace, causing insufficient consideration of the variation of independent factors. Although some recent research analyzes the latent space on pretrained GANs for image editing, they do not emphasize learning representation directly from the subspace perspective. Appropriate subspace properties could facilitate corresponding feature representation learning to satisfy the independent variation requirements of the obtained explanatory factors, which is crucial for better disentanglement. In this work, we propose a unified framework for ensuring disentanglement, which fully investigates latent subspace learning (SL) in GAN. The novel GAN-based architecture explores orthogonal subspace representation (OSR) on vanilla GAN, named OSRGAN. To guide a subspace with strong correlation, less redundancy, and robust distinguishability, our OSR includes three stages, self-latent-aware, orthogonal subspace-aware, and structure representation-aware, respectively. First, the self-latent-aware stage promotes the latent subspace strongly correlated with the data space to discover interpretable factors, but with poor independence of variation. Second, the following orthogonal subspace-aware stage adaptively learns some 1-D linear subspace spanned by a set of orthogonal bases in the latent space. There is less redundancy between them, expressing the corresponding independence. Third, the structure representation-aware stage aligns the projection on the orthogonal subspace and the latent variables. Accordingly, feature representation in each linear subspace can be distinguishable, enhancing the independent expression of interpretable factors. In addition, we design an alternating optimization step, achieving a tradeoff training of OSRGAN on different properties. Despite it strictly constrains orthogonality, the loss weight coefficient of distinguishability induced by orthogonality could be adjusted and balanced with correlation constraint. To elucidate, this tradeoff training prevents our OSRGAN from overemphasizing any property and damaging the expressiveness of the feature representation. It takes into account both interpretable factors and their independent variation characteristics. Meanwhile, alternating optimization could keep the cost and efficiency of forward inference unchanged and will not burden the computational complexity. In theory, we clarify the significance of OSR, which brings better independence of factors, along with interpretability as correlation could converge to a high range faster. Moreover, through the convergence behavior analysis, including the objective functions under different constraints and the evaluation curve with iterations, our model demonstrates enhanced stability and definitely converges toward a higher peak for disentanglement. To depict the performance in downstream tasks, we compared the state-of-the-art GAN-based and even VAE-based approaches on different datasets. Our OSRGAN achieves higher disentanglement scores on FactorVAE, SAP, MIG, and VP metrics. All the experimental results illustrate that our novel GAN-based framework has considerable advantages on disentanglement.

Characterization of an imported HIV-1 A1/A7/G recombinant in China.

BACKGROUND: International migration has accelerated the HIV-1 spread across national borders, gradually reducing the restrictions on the geographical distribution of HIV-1 subtypes. Subtypes A and G are globally recognized as the third and sixth most dominant HIV-1 genotypes, mainly prevalent in Africa, but rarely detected in China. Here we reported an imported HIV-1 recombinant which was composed of sub-subtypes A1 and A7 of subtype A and subtype G genes in a Chinese female. This virus was the first HIV-1 recombinant including A7 genes reported in the world. CASE PRESENTATION: The near full-length genome (NFLG) was obtained from the plasma sample of the female in an HIV-1 molecular epidemiological survey with 853 participants in China. Phylogenetic analyses showed that this NFLG sequence contains three A7 segments, four G segments and one A1 segment with seven breakpoints, and all these segments were closely related to HIV-1 references circulating in Africa. The evidence from epidemiological investigation indicated that this female participant had a more-than-two-years heterosexual contact history with a fixed partner from Nigeria, a country in west Africa, which further supported the results of phylogenetic analyses. By the Bayesian phylogenetic analyses, the times of most recent common ancestors (tMRCA) of the partial pol gene (nt2308-3284, A7 region) and full-length vpr-vpu plus partial env gene (nt5534-6858, G region) were estimated around 1989 and 1984, respectively. CONCLUSIONS: In this study, by using the NFLG sequencing, we identified an imported HIV-1 A1/A7/G recombinant which was estimated to originate around 1980s in Africa and introduced into China with international migration. This study highlighted the complexity of the global HIV-1 epidemic, the necessity of using genome sequences to determine HIV-1 genotypes and the importance of real-time monitoring of HIV-1 infection among international migrants and travelers.

Oral Simnotrelvir for Adult Patients with Mild-to-Moderate Covid-19.

BACKGROUND: Simnotrelvir is an oral 3-chymotrypsin-like protease inhibitor that has been found to have in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential efficacy in a phase 1B trial. METHODS: In this phase 2-3, double-blind, randomized, placebo-controlled trial, we assigned patients who had mild-to-moderate coronavirus disease 2019 (Covid-19) and onset of symptoms within the past 3 days in a 1:1 ratio to receive 750 mg of simnotrelvir plus 100 mg of ritonavir or placebo twice daily for 5 days. The primary efficacy end point was the time to sustained resolution of symptoms, defined as the absence of 11 Covid-19-related symptoms for 2 consecutive days. Safety and changes in viral load were also assessed. RESULTS: A total of 1208 patients were enrolled at 35 sites in China; 603 were assigned to receive simnotrelvir and 605 to receive placebo. Among patients in the modified intention-to-treat population who received the first dose of trial drug or placebo within 72 hours after symptom onset, the time to sustained resolution of Covid-19 symptoms was significantly shorter in the simnotrelvir group than in the placebo group (180.1 hours [95% confidence interval {CI}, 162.1 to 201.6] vs. 216.0 hours [95% CI, 203.4 to 228.1]; median difference, -35.8 hours [95% CI, -60.1 to -12.4]; P = 0.006 by Peto-Prentice test). On day 5, the decrease in viral load from baseline was greater in the simnotrelvir group than in the placebo group (mean difference [±SE], -1.51±0.14 log10 copies per milliliter; 95% CI, -1.79 to -1.24). The incidence of adverse events during treatment was higher in the simnotrelvir group than in the placebo group (29.0% vs. 21.6%). Most adverse events were mild or moderate. CONCLUSIONS: Early administration of simnotrelvir plus ritonavir shortened the time to the resolution of symptoms among adult patients with Covid-19, without evident safety concerns. (Funded by Jiangsu Simcere Pharmaceutical; ClinicalTrials.gov number, NCT05506176.).

Mpox patients' experience from infection to treatment and implications for prevention and control: A multicenter qualitative study in China.

Monkeypox (mpox), a viral zoonotic disease, is spreading worldwide. However, evidence that informs prevention and control strategies in the Asia Pacific Region is very limited. Our study aims to investigate the experiences of mpox patients from infection to treatment to provide scientific basis for the prevention and control. A multicenter qualitative design was used. A total of 15 mpox patients were recruited between July 6 and July 25, 2023, from six cities in China. Semistructured interviews were conducted by telephone and analyzed using the thematic analysis. The interview was divided into two sections: patients' experiences (prediagnosis experience, treatment-seeking experience, and quarantine experience) and advice. Prediagnosis experience was summarized into three themes: symptoms, possible routes of infection, and knowledge of mpox. Treatment-seeking experience was summarized into three themes: time of visit to hospital, diagnostic difficulties, and attitude toward diagnosis. Quarantine experience was summarized into three themes: body and mind reactions, reluctance to self-disclose infection status, and factors facilitating recovery. Themes identified from patients' advice were as follows: (1) Increase in testing channels and methods, (2) Development and introduction of vaccines, (3) Adjustment of quarantine program, (4) Improvement of treatment measures, and (5) Improvement of publicity and education. To effectively curb the mpox epidemic, structured measures are urgently needed to address the mpox-related stigma and discrimination. Targeted health education should be provided to MSM, focusing on the prevention, detection, and treatment services. Hospitals should enhance the training of clinicians in key departments including infectious disease and dermatology, to improve diagnostic capability and sensitivity. Furthermore, given the absence of specific antiviral medications, supervised home quarantine may be a good option.

Development of a quadruple qRT-PCR assay for simultaneous identification of hypervirulent and carbapenem-resistant Klebsiella pneumoniae.

IMPORTANCE: Globally, the increasing number of hypervirulent Klebsiella pneumoniae (hvKp) and carbapenem-resistant Kp (CR-Kp) infections poses a huge public health challenge with high morbidity and mortality. Worrisomely, due to the mobility of elements carrying virulence and drug-resistance genes, the increasing prevalence of CR-hvKp has also been found with an overwhelming mortality rate in recent years. However, the current detection methods for hvKp and CR-Kp have many disadvantages, such as long turnaround time, complex operation, low sensitivity, and specificity. Herein, a more sensitive, rapid, single-reaction, and multiplex quantitative real-time PCR was developed and validated to differentiate the circulating lineages of Kp with excellent performance in sensitivity and specificity, providing a useful tool for the differential diagnosis and the surveillance of the circulating Kp.

The correlation of lymphocytes with disease progression of COVID-19.

The aim of this study is to evaluate the potential of lymphocytes as biomarkers to predict the decline of coronavirus disease 2019 (COVID-19). Lymphocytes were counted in 164 moderate COVID-19 patients in Shenzhen, China. Among the moderate infected patients, 12.2% (20/164) progressed to severe cases after admission. Compared with the stable patients, the counts of lymphocytes, both total T lymphocytes and CD4+ T lymphocytes, in the severe patients, were lower. The aggravation of moderate infected patients was significantly associated with lymphocyte count (hazard ratio [HR] = 0.91; 95% confidence interval [CI]: 0.84-0.99), total T lymphocyte count (HR = 0.91; 95% CI: 0.84-0.99), and CD4+ T lymphocyte count (HR = 0.91; 95% CI: 0.85-0.98). Total T lymphocytes and CD4+ T lymphocytes could be important biomarkers to evaluate the risk of aggravation for moderate infected COVID-19 patients. The patients with low percentages of total T lymphocytes and CD4+ T lymphocytes need more attention.

Risk factors of oncogenic HPV infection in HIV-positive men with anal condyloma acuminata in Shenzhen, Southeast China: a retrospective cohort study.

Background: Human immunodeficiency virus (HIV)-positive patients with anal condyloma acuminata (CA) present an increased risk of anal cancer progression associated with oncogenic human papillomavirus (HPV) infection. It is essential to explore determinants of anal infection by oncogenic HPV among HIV-positive patients with CA. Methods: A retrospective cohort study was performed in HIV-positive patients with CA between January 2019 to October 2021 in Shenzhen, Southeast China. Exfoliated cells were collected from CA lesions and the anal canal of HPV genotypes detected by fluorescence PCR. Unconditional logistic regression analysis was used to probe associations of independent variables with oncogenic HPV infection. Results: Among HIV-positive patients with CA, the most prevalent oncogenic genotypes were HPV52 (29.43%), HPV16 (28.93%), HPV59 (19.20%), and HPV18 (15.96%). Risk of oncogenic HPV infection increased with age at enrollment (COR: 1.04, 95% CI: 1.01-1.07, p = 0.022). In the multivariable analysis, age ≥ 35 years (AOR: 2.56, 95% CI: 1.20-5.70, p = 0.02) and history of syphilis (AOR: 3.46, 95% CI: 1.90-6.79, p < 0.01) were independent risk factors statistically associated with oncogenic HPV infection. History of syphilis (AOR: 1.72, 95% CI: 1.08-2.73, p < 0.02) was also an independent risk factor statistically associated with HPV16 or HPV18 infection. Conclusion: In clinical practice, HIV-positive CA patients aged ≥35 years or with a history of syphilis should carry out HR-HPV testing and even anal cancer-related examinations to prevent the occurrence of anal cancer.

Chinese expert consensus on the management of patients with hematologic malignancies infected with SARS-CoV-2.

In December 2022, the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became dominant in China due to its high infectivity and lower mortality rate. The risk of critical illness and mortality among patients with hematologic malignancies who contracted SARS-CoV-2 was particularly high. The aim of this study was to draft a consensus to facilitate effective treatments for these patients based on the type and severity of the disease. Following the outbreak of the novel coronavirus in China, a steering committee consisting of experienced hematologists was formed by the Specialized Committee of Oncology and Microecology of the Chinese Anti-Cancer Association. The expert group drafted a consensus on the management and intervention measures for different types of hematologic malignancies based on the clinical characteristics of the Omicron variant of the SARS-CoV-2 infection, along with relevant guidelines and literature. The expert group drafted independent recommendations on several important aspects based on the epidemiology of the Omicron variant in China and the unique vulnerability of patients with hematologic malignancies. These included prophylactic vaccinations for those with hematologic malignancies, the use of plasma from blood donors who recovered from the novel coronavirus infection, the establishment of negative pressure wards, the use of steady-state mobilization of peripheral blood hematopoietic stem cells, the provision of psychological support for patients and medical staff, and a focus on maintaining a healthy intestinal microecology.

Analysis of multiple organ function damage in patients with severe COVID-19 pneumonia.

Background: This study aims to analyze the changes and significance of organ function indices in patients with severe Coronavirus Disease 2019 (COVID-19) pneumonia for prediction of major organ damages and guiding treatment schemes. Methods: 63 patients with severe COVID-19 pneumonia were selected as the severe group and 73 patients with mild syndromes were selected as the mild group. SAS9.4 software was used for statistical analysis of the data. Results: Levels of ALT, AST, cTnI, Cr, PT, APTT and Ddimer of the severe group were significantly higher while PLT was lower than those of the mild group. The data of all quantitative variables were converted into categorical variables. Significantly higher levels of AST, ALB, D-dimer and higher proportion of bilateral lung involvement were observed from the severe group comparing to those in the mild group, while the difference in the other indices between the two groups was insignificant in statistical perspective. Conclusions: There are significant differences in the levels of multiple organ function indices between the severe group and the mild group of patients with COVID-19 pneumonia infection. Through examining the relevant indices, conditions of patients' multiple organ function damage could be predicted and used as guidance of treatment.

Epidemiological characteristics, clinical manifestations, and mental health status of human mpox cases: A multicenter cross-sectional study in China.

Human mpox is occurring worldwide, however, evidence from the Asian Pacific Region is limited. In this multicenter cross-sectional study, information of confirmed mpox cases diagnosed between June 1 and July 31, 2023 in China. Information included demographic and epidemiological characteristics, and clinical manifestations, laboratory results, and mental health status of mpox cases. A total of 115 confirmed mpox cases were enrolled. All cases were men. A total of 102 (90.3%) identified as homosexual. The median age was 31.0 years (interquartile range 27.0-36.5). A total of 65 (56.5%) were HIV-positive, of whom 92.3% were receiving antiretroviral therapy (ART). A total of 19/39 (40.4%) had a CD4 cell count <500 cells/µL. Systemic features such as fever (73.0%), lymphadenopathies (49.6%), and myalgia (28.7%) were commonly observed. Skin lesions were present in all participants: 49.6% in the genital area and 27.0% in the perianal area. Vesicular rash (78.3%) and papular rash (44.3%) were the most common lesion morphologies. People living with HIV were more likely to have anxiety than those living without HIV. The majority of mpox cases had primary genital lesions and sexual activities before diagnosis, which supports the likelihood of sexual contact transmission. Guidelines on hospitalization and isolation protocols for mpox patients necessitate further confirmation.

Case Report: Mycobacterium kansasii causing infective endocarditis explored by metagenomic next-generation sequencing.

In this report, we describe the first case of infective endocarditis caused by Mycobacterium kansasii in a 45-year-old male patient who presented with a 10-day fever and decompensated cirrhosis. Despite negative results in blood culture and pathology, we employed metagenomic next-generation sequencing (mNGS) to analyze the genome sequences of both the host and microbe. The copy number variation (CNV) indicated a high risk of liver disease in the patient, which correlated with biochemical examination findings. Notably, M. kansasii sequences were detected in peripheral blood samples and confirmed through Sanger sequencing. Unfortunately, the patient's condition deteriorated, leading to his demise prior to heart surgery. Nevertheless, we propose that mNGS could be a novel approach for diagnosing M. kansasii infection, particularly in cases where blood culture and pathology results are unavailable. It is important to consider M. kansasii infection as a potential cause of endocarditis and initiate appropriate anti-infection treatment.

An ultrasensitive photoelectrochemical assay for tumor necrosis factor-alpha based on hollow CdS cubes as a signal generator and NiCo2O4-Au as a signal extinguisher.

Sensitive detection of tumor necrosis factor-alpha (TNF-α) in human serum is beneficial for finding cancer patients early due to overexpressed TNF-α being related to some cancers. Here, a photoelectrochemical (PEC) aptasensor was constructed for ultrasensitive TNF-α assay based on the signal generator of hollow CdS cubes (H-CdS) and the signal extinguishing activity of NiCo2O4-Au. In this work, compared with traditional solid CdS, H-CdS could greatly promote the PEC signal because its hollow structure could accelerate the separation of photogenerated charges, which also possesses abundant active sites and high light absorption capability. Moreover, H-CdS can be prepared facilely with Cd-based Prussian blue analogs as the precursor. Meanwhile, NiCo2O4-Au was fabricated and utilized as a signal extinguisher. In the presence of TNF-α, NiCo2O4-Au could be introduced onto the H-CdS modified electrode, producing competitive consumption of the electron donor effect, the p-n semiconductor quenching effect, and the mimetic enzymatic catalytic precipitation effect, which all can significantly reduce the PEC signal. Based on the signal extinguishing activity of NiCo2O4-Au and the signal generator of H-CdS, TNF-α can be detected sensitively with a lower detection limit (0.63 fg mL-1) and a wide linear range (1 fg mL-1- to 1 ng mL-1), which may have a potential application in the PEC bioanalysis field and the disease diagnostics field.

Striking antibody evasion of SARS-CoV-2 Omicron sub-lineages BQ.1.1, XBB.1 and CH.1.1.

An intelligent indoor metasurface robotic is empowered on the physical layer by programmable metasurfaces and on the cyber layer by artificial-intelligence tools.

Efficacy and safety of SIM0417 (SSD8432) plus ritonavir for COVID-19 treatment: a randomised, double-blind, placebo-controlled, phase 1b trial.

Background: SIM0417 (SSD8432) is an orally administered coronavirus main proteinase (3CLpro) inhibitor with potential anti-SARS-CoV-2 activity. This study aimed to evaluate the efficacy and safety of SIM0417 plus ritonavir (a pharmacokinetic enhancer) in adults with COVID-19. Methods: This was a randomised, double-blind, placebo-controlled, phase 1b study in China. Adults with asymptomatic infection, mild or moderate COVID-19 were randomly assigned (3:3:2) to receive either 750 mg SIM0417 plus 100 mg ritonavir, 300 mg SIM0417 plus 100 mg ritonavir or placebo every 12 h for 10 doses. The main efficacy endpoints included SARS-CoV-2 viral load, proportion of participants with positive SARS-CoV-2 nucleic acid test and time to alleviation of COVID-19 symptoms. This trial is registered with ClinicalTrials.gov, NCT05369676. Findings: Between May 12 and August 29, 2022, 32 participants were enrolled and randomised to high dose group (n = 12), low dose group (n = 12) or placebo (n = 8). The viral load change from baseline in high dose group was statistically lower compared with placebo, with a maximum mean difference of -2.16 ± 0.761 log10 copies/mL (p = 0.0124) on Day 4. The proportion of positive SARS-CoV-2 in both active groups were lower than the placebo. The median time to sustained alleviation of COVID-19 symptoms was 2.0 days in high dose group versus 6.0 days in the placebo group (HR = 3.08, 95% CI 0.968-9.818). SIM0417 plus ritonavir were well tolerated with all adverse events in grade 1. Interpretation: SIM0417 plus ritonavir was generally well tolerated. The efficacy of SIM0417 showed a monotonic dose-response relationship, and the 750 mg SIM0417 plus 100 mg ritonavir was selected as the recommended clinical dose. Funding: The study was funded by Jiangsu Simcere Pharmaceutical Co., Ltd.

Hyperglycosylated N-Linked Site 339 of gp120 Appears to Be Unique and May Contribute to CRF01_AE Transmission Among Men Who Have Sex with Men in China and Thailand.

Human immunodeficiency virus (HIV)-1 CRF01_AE is one of the most important genotypes in China, especially in the population of men who have sex with men (MSM). It has become the most prevalent strain among them. Describing the variant characterization of CRF01_AE will help to reveal the reason behind its predominance in MSM. In this study, the complete DNA sequences (CDSs) for gp120 from the envelope protein (env) gene of CRF01_AE in China and Thailand were retrieved from the Los Alamos HIV database. The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDU), heterosexual contacts (HC), and MSM. The N-linked CDS glycosylation sites for gp120 in CRF01_AE were analyzed. The results showed a unique hyperglycosylation site N-339 (refer to Hxb2) in the gp120 of CRF01_AE in MSM compared with the IDU and HC groups from China. The result was the same in the MSM group from Thailand, which suggests that the hyperglycosylation site N-339 may explain the widespread CRF01_AE genotype in MSM.

Xylenol orange-modified CdTe quantum dots as a fluorescent/colorimetric dual-modal probe for anthrax biomarker based on competitive coordination.

Bacillus anthracis spores can make humans infected with vicious anthrax, so it is significant to detect their biomarker 2,6-pyridinedicarboxylic acid (DPA). The development of dual-modal methods for DPA detection that are more flexible in practical applications remains a challenge. Herein, colorimetric xylenol orange (XO) was modified on fluorescent CdTe quantum dots (QDs) for dual-modal detection of DPA through competitive coordination. After the binding of XO on CdTe QDs via coordination with Cd2+, CdTe QDs displayed quenched red fluorescence and the bound XO was presented as red color. The competitive coordination of DPA with Cd2+ made XO released from CdTe QDs, causing the enhanced red fluorescence of CdTe QDs and the yellow color of free XO. On this basis, DPA was rapidly (1 min) quantified through fluorescent and colorimetric modes within the ranges of 0.1-5 µM and 0.5-40 µM, respectively. The detection limits for DPA were calculated as low as 42 nM and 240 nM, respectively assigned to fluorescent and colorimetric modes. The level of urinary DPA was further measured. Satisfactory relative standard deviations (fluorescent mode: 0.1%-10.2%, colorimetric mode: 0.8%-1.8%) and spiked recoveries (fluorescent mode: 100.0%-115.0%, colorimetric mode: 86.0%-96.6%) were obtained.