Pan-cancer scRNA-seq analysis reveals immunological and diagnostic significance of the peripheral blood mononuclear cells.

Peripheral blood mononuclear cells (PBMCs) reflect systemic immune response during cancer progression. However, a comprehensive understanding of the composition and function of PBMCs in cancer patients is lacking, and the potential of these features to assist cancer diagnosis is also unclear. Here, the compositional and status differences between cancer patients and healthy donors in PBMCs were investigated by single-cell RNA sequencing (scRNA-seq), involving 262,025 PBMCs from 68 cancer samples and 14 healthy samples. We observed an enhanced activation and differentiation of most immune subsets in cancer patients, along with reduction of naïve T cells, expansion of macrophages, impairment of NK cells and myeloid cells, as well as tumor promotion and immunosuppression. Based on characteristics including differential cell type abundances and/or hub genes identified from weight gene co-expression network analysis (WGCNA) modules of each major cell type, we applied logistic regression to construct cancer diagnosis models. Furthermore, we found that the above models can distinguish cancer patients and healthy donors with high sensitivity. Our study provided new insights into using the features of PBMCs in non-invasive cancer diagnosis.

EphA2 is a functional entry receptor for HCMV infection of glioblastoma cells.

Human cytomegalovirus (HCMV) infection is associated with human glioblastoma, the most common and aggressive primary brain tumor, but the underlying infection mechanism has not been fully demonstrated. Here, we show that EphA2 was upregulated in glioblastoma and correlated with the poor prognosis of the patients. EphA2 silencing inhibits, whereas overexpression promotes HCMV infection, establishing EphA2 as a crucial cell factor for HCMV infection of glioblastoma cells. Mechanistically, EphA2 binds to HCMV gH/gL complex to mediate membrane fusion. Importantly, the HCMV infection was inhibited by the treatment of inhibitor or antibody targeting EphA2 in glioblastoma cells. Furthermore, HCMV infection was also impaired in optimal glioblastoma organoids by EphA2 inhibitor. Taken together, we propose EphA2 as a crucial cell factor for HCMV infection in glioblastoma cells and a potential target for intervention.

The formation of Jupiter's diluted core by a giant impact.

The Juno mission1 has provided an accurate determination of Jupiter's gravitational field2, which has been used to obtain information about the planet's composition and internal structure. Several models of Jupiter's structure that fit the probe's data suggest that the planet has a diluted core, with a total heavy-element mass ranging from ten to a few tens of Earth masses (about 5 to 15 per cent of the Jovian mass), and that  heavy elements (elements other than hydrogen and helium) are distributed within a region extending to nearly half of Jupiter's radius3,4. Planet-formation models indicate that most heavy elements are accreted during the early stages of a planet's formation to create a relatively compact core5-7 and that almost no solids are accreted during subsequent runaway gas accretion8-10. Jupiter's diluted core, combined with its possible high heavy-element enrichment, thus challenges standard planet-formation theory. A possible explanation is erosion of the initially compact heavy-element core, but the efficiency of such erosion is uncertain and depends on both the immiscibility of heavy materials in metallic hydrogen and on convective mixing as the planet evolves11,12. Another mechanism that can explain this structure is planetesimal enrichment and vaporization13-15 during the formation process, although relevant models typically cannot produce an extended diluted core. Here we show that a sufficiently energetic head-on collision (giant impact) between a large planetary embryo and the proto-Jupiter could have shattered its primordial compact core and mixed the heavy elements with the inner envelope. Models of such a scenario lead to an internal structure that is consistent with a diluted core, persisting over billions of years. We suggest that collisions were common in the young Solar system and that a similar event may have also occurred for Saturn, contributing to the structural differences between Jupiter and Saturn16-18.

Author Correction: The mid-developmental transition and the evolution of animal body plans.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Polylevodopa nanoplatform for lateral flow immunochromatography assay of SARS-CoV-2 and influenza A virus.

At the end of 2019, an unprecedented outbreak of novel coronavirus pneumonia ravaged the global landscape, inflicting profound harm upon society. Following numerous cycles of transmission, we find ourselves in an epoch where the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coexists alongside influenza viruses (Flu A). Swift and accurate diagnosis of SARS-CoV-2 and Flu A is imperative to stem the spread of these maladies and administer appropriate treatment. Presently, colloidal gold-based lateral flow immunoassays (Au-LFIAs) constructed through electrostatic adsorption are beset by challenges such as diminished sensitivity and feeble binding stability. In this context, we propose the adoption of black polylevodopa nanoparticles (PLDA NPs) featuring abundant carboxyl groups as labeling nanomaterials in LFIA to bolster the stability and sensitivity of SARS-CoV-2 antigens and influenza A virus identifications. The engineered PLDA-LFIAs exhibit the capacity to detect SARS-CoV-2 and Flu A within 30 min, boasting a detection threshold of 5 pg/ml for the SARS-CoV-2 antigen and 0.1 ng/ml for the Flu A H1N1 antigen, thereby underscoring their heightened sensitivity relative to Au-LFIAs. These PLDA-LFIAs hold promise for the early detection of SARS-CoV-2 and Flu A, underscoring the potential of PLDA NPs as a discerning labeling probe to heighten the sensitivity of LFIA across diverse applications.

IRF8 deficiency-induced myeloid-derived suppressor cell promote immune evasion in lung adenocarcinoma.

BACKGROUND: Patients with lung adenocarcinoma (LUAD) have a low response rate to immune checkpoint blockade. It is highly important to explore the tumor immune escape mechanism of LUAD patients and expand the population of patients who may benefit from immunotherapy. METHODS: Based on 954 bulk RNA-seq data of LUAD patients and 15 single-cell RNA-seq data, the relationships between tumor immune dysfunction and exclusion (TIDE) scores and survival prognosis in each patient were calculated and evaluated, and the immune escape mechanism affecting the independent prognosis of LUAD patients was identified. Functional enrichment analysis explored the antitumour immune response and biological behavior of tumor cells among different LUAD groups. Single-cell annotation and pseudotemporal analysis were used to explore the target molecules and immune escape mechanisms of LUAD. RESULTS: Myeloid-derived suppressor cells (MDSCs) and IRF8 were identified as risk and protective factors for the independent prognosis of LUAD patients, respectively. In the tumor microenvironment of patients with high infiltration of MDSCs, the antitumor immune response is significantly suppressed, while tumor cell division, proliferation, and distant metastasis are significantly enhanced. Single-cell RNA-seq analysis revealed that IRF8 is an important regulator of MDSC differentiation in LUAD myeloid cells. In addition, IRF8 may regulate the differentiation of MDSCs through the IL6-JAK-STAT3 signalling pathway. CONCLUSIONS: IRF8 deficiency impairs the normal development of LUAD myeloid cells and induces their differentiation into MDSCs, thereby accelerating the immune escape of LUAD cells. IRF8-targeted activation to inhibit the formation of MDSCs may be a new target for immunotherapy in LUAD.

Whole-brain mapping of monosynaptic afferent inputs to the CRH neurons in the medial prefrontal cortex of mice.

Corticotropin-releasing hormone (CRH) neurons are densely distributed in the medial prefrontal cortex (mPFC), which plays a crucial role in integrating and processing emotional and cognitive inputs from other brain regions. Therefore, it is important to know the neural afferent patterns of mPFCCRH neurons, which are still unclear. Here, we utilized a rabies virus-based monosynaptic retrograde tracing system to map the presynaptic afferents of the mPFCCRH neurons throughout the entire brain. The results show that the mPFCCRH neurons receive inputs from three main groups of brain regions: (1) the cortex, primarily the orbital cortex, somatomotor areas, and anterior cingulate cortex; (2) the thalamus, primarily the anteromedial nucleus, mediodorsal thalamic nucleus, and central medial thalamic nucleus; and (3) other brain regions, primarily the basolateral amygdala, hippocampus, and dorsal raphe nucleus. Taken together, our results are valuable for further investigations into the roles of the mPFCCRH neurons in normal and neurological disease states. These investigations can shed light on various aspects such as cognitive processing, emotional modulation, motivation, sociability, and pain.

pH-Responsive Sorafenib/Iron-Co-Loaded Mesoporous Polydopamine Nanoparticles for Synergistic Ferroptosis and Photothermal Therapy.

Ferroptosis has attracted significant attention as a new mechanism of cell death. Sorafenib (SRF) is widely considered a prototypical ferroptosis-inducing drug, particularly for liver cancer treatment. However, the low solubility and hydrophobic nature of SRF, along with the absence of synergistic therapeutic strategies, still limit its application in cancer treatment. Herein, we report a dual therapeutic method incorporating photothermal therapy and ferroptosis by using Fe-doped mesoporous polydopamine nanoparticles (Fe-mPDA@SRF-TPP) as a carrier for loading SRF and targeting triphenylphosphine (TPP). SRF molecules are efficiently encapsulated within the polydopamine nanospheres with a high loading ratio (80%) attributed to the porosity of Fe-mPDA, and the inherent biocompatibility and hydrophilicity of Fe-mPDA@SRF-TPP facilitate the transport of SRF to the target cancer cells. Under the external stimuli of acidic environment (pH 5.0), glutathione (GSH), and laser irradiation, Fe-mPDA@SRF-TPP shows sustained release of SRF and Fe ions with the ratio of 72 and 50% within 48 h. Fe-mPDA@SRF-TPP nanoparticles induce intracellular GSH depletion, inhibit glutathione peroxidase 4 (GPX4) activity, and generate hydroxyl radicals, all of which are essential components of the therapeutic ferroptosis process for killing MDA-MB-231 cancer cells. Additionally, the excellent near-infrared (NIR) light absorption of Fe-mPDA@SRF-TPP nanoparticles demonstrates their capability for photothermal therapy and further enhances the therapeutic efficiency. Therefore, this nanosystem provides a multifunctional therapeutic platform that overcomes the therapeutic limitations associated with standalone ferroptosis and enhances the therapeutic efficacy of SRF for breast cancer.

Subthalamic stimulation modulates motor network in Parkinson's disease: recover, relieve and remodel.

Aberrant dynamic switches between internal brain states are believed to underlie motor dysfunction in Parkinson's disease. Deep brain stimulation of the subthalamic nucleus is a well-established treatment for the motor symptoms of Parkinson's disease, yet it remains poorly understood how subthalamic stimulation modulates the whole-brain intrinsic motor network state dynamics. To investigate this, we acquired resting-state functional magnetic resonance imaging time-series data from 27 medication-free patients with Parkinson's disease (mean age: 64.8 years, standard deviation: 7.6) who had deep brain stimulation electrodes implanted in the subthalamic nucleus, in both on and off stimulation states. Sixteen matched healthy individuals were included as a control group. We adopted a powerful data-driven modelling approach, known as a hidden Markov model, to disclose the emergence of recurring activation patterns of interacting motor regions (whole-brain intrinsic motor network states) via the blood oxygen level-dependent signal detected in the resting-state functional magnetic resonance imaging time-series data from all participants. The estimated hidden Markov model disclosed the dynamics of distinct whole-brain motor network states, including frequency of occurrence, state duration, fractional coverage and their transition probabilities. Notably, the data-driven decoding of whole-brain intrinsic motor network states revealed that subthalamic stimulation reshaped functional network expression and stabilized state transitions. Moreover, subthalamic stimulation improved motor symptoms by modulating key trajectories of state transition within whole-brain intrinsic motor network states. This modulation mechanism of subthalamic stimulation was manifested in three significant effects: recovery, relieving and remodelling effects. Significantly, recovery effects correlated with improvements in tremor and posture symptoms induced by subthalamic stimulation (P < 0.05). Furthermore, subthalamic stimulation was found to restore a relatively low level of fluctuation of functional connectivity in all motor regions to a level closer to that of healthy participants. Also, changes in the fluctuation of functional connectivity between motor regions were associated with improvements in tremor and gait symptoms (P < 0.05). These findings fill a gap in our knowledge of the role of subthalamic stimulation at the level of neural activity, revealing the regulatory effects of subthalamic stimulation on whole-brain inherent motor network states in Parkinson's disease. Our results provide mechanistic insight and explanation for how subthalamic stimulation modulates motor symptoms in Parkinson's disease.

Cutoff values of axial length/corneal radius ratio for determining myopia vary with age among 3-18 years old children and adolescents.

PURPOSE: To investigate the effectiveness and cutoffs of axial length/corneal radius (AL/CR) ratio for myopia detection in children by age. METHODS: Totally, 21 kindergartens and schools were enrolled. Non-cycloplegic autorefraction (NCAR), axial length (AL), horizontal and vertical meridian of corneal radius (CR1, CR2), and cycloplegic autorefraction were measured. Receiver operating characteristic (ROC) curve was used to obtain the effectiveness and cutoff for myopia detection. RESULTS: Finally, 7803 participants aged 3-18 years with mean AL/CR ratio of 2.99 ± 0.16 were included. Area under the ROC curve (AUC) of AL/CR ratio for myopia detection (0.958 for AL/CR1, 0.956 for AL/CR2, 0.961 for AL/CR) was significantly larger than that of AL (0.919, all P < 0.001), while AUCs of the three were similar with different cutoffs (> 2.98, > 3.05, and > 3.02). When divided by age, the ROC curves of AL/CR ratio in 3- to 5-year-olds showed no significance or low accuracy (AUCs ≤ 0.823) in both genders. In ≥ 6-year-olds, the accuracies were promising (AUCs ≥ 0.883, all P < 0.001), the cutoffs basically increased with age (from > 2.93 in 6-year-olds to > 3.07 in 18-year-olds among girls, and from > 2.96 in 6-year-olds to > 3.07 in 18-year-olds among boys). In addition, boys presented slightly larger cutoffs than girls in all ages except for 16 and 18 years old. For children aged 3-5 years, AL/CR ratio or AL combined with NCAR increased AUC to > 0.900. CONCLUSION: AL/CR ratio provided the best prediction of myopia with age-dependent cutoff values for all but preschool children, and the cutoffs of boys were slightly larger than those of girls. For preschool children, AL/CR ratio or AL combined with NCAR is recommended to achieve satisfactory accuracy. AL/CR ratio calculated by two meridians showed similar predictive power but with different cutoffs.

Sea spray aerosol concentration modulated by sea surface temperature.

Natural aerosols in pristine regions form the baseline used to evaluate the impact of anthropogenic aerosols on climate. Sea spray aerosol (SSA) is a major component of natural aerosols. Despite its importance, the abundance of SSA is poorly constrained. It is generally accepted that wind-driven wave breaking is the principle governing SSA production. This mechanism alone, however, is insufficient to explain the variability of SSA concentration at given wind speed. The role of other parameters, such as sea surface temperature (SST), remains controversial. Here, we show that higher SST promotes SSA mass generation at a wide range of wind speed levels over the remote Pacific and Atlantic Oceans, in addition to demonstrating the wind-driven SSA production mechanism. The results are from a global scale dataset of airborne SSA measurements at 150 to 200 m above the ocean surface during the NASA Atmospheric Tomography Mission. Statistical analysis suggests that accounting for SST greatly enhances the predictability of the observed SSA concentration compared to using wind speed alone. Our results support implementing SST into SSA source functions in global models to better understand the atmospheric burdens of SSA.

Californium-252 Intracavitary Radiotherapy for Primary Vaginal Carcinoma: A Retrospective Clinical Study.

Objective: To investigate the therapeutic effect of Cf-252 neutron intracavitary brachytherapy (ICBT) in the treatment of primary vaginal carcinoma of stage I-III, along with advanced complications. Methods: Between August 2009 and August 2013, 41 patients with intact primary vaginal carcinoma based on the histological diagnosis at the Second Cancer Hospital of Heilongjiang Province (Beidahuang Group General Hospital) and the Daping Hospital of the Third Military Medical University were included in this study. Among them, 32 patients were squamous cell carcinoma, and 9 adenocarcinomas. Stage I patients were treated with ICBT alone. Patients at stages II and III were treated using ICBT combined with external beam radiotherapy (EBRT). Results: The mean age, the rate of the 5-year local control, the rate of the 5-year overall survival was increased. The rate of the 5-year tumor-free survival was 56.1%, and the incidence of advanced serious complications (grade II and above radiation cystitis, proctitis, etc.) was 29.3%. Compared to later stages, early-stage patients are in better physical shape, so they are better able to withstand the toxic side effects of treatment. The local control (LC), overall survival (OS), or disease-free survival (DFS) rate in stage III patients was significantly lower than those in stage I and stage II. The rate of OS in stage I patients was 90.9% (10/11), which was significantly higher than that in all patients (56.1%; 23/41). Moreover, the mean survival time was significantly different between stage III and stage I. In addition, the survival status of squamous cell carcinoma and adenocarcinoma was also very different. Conclusion: In summary, the use of Cf-252 ICBT radiotherapy resulted in a higher rate of local control of vaginal cancer and a lower rate of recurrence, better-shrinking effect, and efficacy for advanced tumors, and has clinical prospects.

A Deep Learning Model Enhances Clinicians' Diagnostic Accuracy to More Than 96% for Anterior Cruciate Ligament Ruptures on Magnetic Resonance Imaging.

PURPOSE: To develop a deep learning model to accurately detect anterior cruciate ligament (ACL) ruptures on magnetic resonance imaging (MRI) and to evaluate its effect on the diagnostic accuracy and efficiency of clinicians. METHODS: A training dataset was built from MRIs acquired from January 2017 to June 2021, including patients with knee symptoms, irrespective of ACL ruptures. An external validation dataset was built from MRIs acquired from January 2021 to June 2022, including patients who underwent knee arthroscopy or arthroplasty. Patients with fractures or prior knee surgeries were excluded in both datasets. Subsequently, a deep learning model was developed and validated using these datasets. Clinicians of varying expertise levels in sports medicine and radiology were recruited, and their capacities in diagnosing ACL injuries in terms of accuracy and diagnosing time were evaluated both with and without artificial intelligence (AI) assistance. RESULTS: A deep learning model was developed based on the training dataset of 22,767 MRIs from 5 centers and verified with external validation dataset of 4,086 MRIs from 6 centers. The model achieved an area under the receiver operating characteristic curve of 0.987 and a sensitivity and specificity of 95.1%. Thirty-eight clinicians from 25 centers were recruited to diagnose 3,800 MRIs. The AI assistance significantly improved the accuracy of all clinicians, exceeding 96%. Additionally, a notable reduction in diagnostic time was observed. The most significant improvements in accuracy and time efficiency were observed in the trainee groups, suggesting that AI support is particularly beneficial for clinicians with moderately limited diagnostic expertise. CONCLUSIONS: This deep learning model demonstrated expert-level diagnostic performance for ACL ruptures, serving as a valuable tool to assist clinicians of various specialties and experience levels in making accurate and efficient diagnoses. LEVEL OF EVIDENCE: Level III, retrospective comparative case series.

Ovarian stimulation response and fertility outcomes in patients with breast cancer across different stages, grades, and hormone receptor status for fertility preservation.

BACKGROUND: This study aimed to explore the potential impact of stage, grade, and hormone receptor profile on ovarian stimulation response and fertility preservation outcomes. METHODS: This retrospective cohort study evaluated data from breast cancer patients who underwent fertility preservation at a tertiary medical center between 2014 and 2022. The outcomes of women with low-stage cancer (stages I and II) were compared with those of women with high-stage disease (stages III and IV or lymph node metastasis). Similarly, we compared those with low-grade (grades 1 and 2) and high-grade (grade 3) malignancies. In addition, we compared different hormone statuses of breast cancer (1) estrogen receptor (ER) positive vs. ER-negative and (2) triple-negative breast cancer (TNBC) vs. non-TNBC. The primary outcome measured was the number of mature oocytes, while the secondary outcomes included the numbers of total oocytes retrieved, peak estradiol levels, and subsequent fertility preservation outcomes. RESULTS: A total of 47 patients were included. Patients with high-grade tumors had a comparable number of mature oocytes (8 vs. 10, p = 0.08) compared to patients with low grade cancers. The stage-based analysis revealed a similar number of mature oocytes (8 vs. 10, p = 0.33) between high/low stage patients. In the hormone receptor-based analysis, no differences were seen in mature oocytes collected between the ER-positive/ER-negative group (9 vs. 9, p = 0.87) and the TNBC/non-TNBC group (11 vs. 9, p = 0.13). The utilization rate was 27.6% (13/47). CONCLUSION: Our study showed similar ovarian stimulation response and fertility preservation outcomes among breast cancer patients with different prognostic factors.

A Novel Intelligent Fault Diagnosis Method for Bearings with Multi-Source Data and Improved GASA.

In recent years, single-source-data-based deep learning methods have made considerable strides in the field of fault diagnosis. Nevertheless, the extraction of useful information from multi-source data remains a challenge. In this paper, we propose a novel approach called the Genetic Simulated Annealing Optimization (GASA) method with a multi-source data convolutional neural network (MSCNN) for the fault diagnosis of rolling bearing. This method aims to identify bearing faults more accurately and make full use of multi-source data. Initially, the bearing vibration signal is transformed into a time-frequency graph using the continuous wavelet transform (CWT) and the signal is integrated with the motor current signal and fed into the network model. Then, a GASA-MSCNN fault diagnosis method is established to better capture the crucial information within the signal and identify various bearing health conditions. Finally, a rolling bearing dataset under different noisy environments is employed to validate the robustness of the proposed model. The experimental results demonstrate that the proposed method is capable of accurately identifying various types of rolling bearing faults, with an accuracy rate reaching up to 98% or higher even in variable noise environments. The experiments reveal that the new method significantly improves fault detection accuracy.

Impact of Telemedicine on Blood Glucose Control and Ophthalmic Screenings for Patients with Diabetes in Remote Areas During the COVID-19 Pandemic: A Real-World Study in Northern Taiwan.

Introduction: The purpose of this study was to assess the impact of telemedicine on ophthalmic screening and blood glucose control for patients with diabetes in remote areas of Northern Taiwan during the coronavirus disease 2019 (COVID-19) pandemic. Methods: Telemedicine was implemented in Shiding and Wanli Districts using a 5G platform from April 2021 to December 2022. Patients with poorly controlled diabetes received real-time consultations from endocrinologists at Far Eastern Memorial Hospital, 50 km away, for medication adjustment, diet control, and lifestyle recommendations. The study also provided cloud-upload blood glucose meters for self-monitoring and regular medical advice from hospital nurses. Ophthalmic screenings included fundus imaging, external eye image, and intraocular pressure measurement, with instant communication and diagnosis by ophthalmologists through telemedicine. A satisfaction questionnaire survey was conducted. Results: The study enrolled 196 patients with diabetes. Blood glucose and glycosylated hemoglobin levels were significantly reduced after applying telemedicine (p = 0.01 and p = 0.005, respectively). Ophthalmic screenings led to hospital referrals for 16.0% with abnormal fundus images, 15.6% with severe cataract or anterior segment disorders, and 27.9% with ocular hypertension or glaucoma. Fundus screening rates remained high at 86.3% and 80.4% in 2022, mainly using telemedicine, comparable with the traditional screening rate in the past 5 years. The overall satisfaction rate was 98.5%. Conclusions: Telemedicine showed effectiveness and high satisfaction in managing diabetes and conducting ophthalmic screenings in remote areas during the COVID-19 pandemic. It facilitated early diagnosis and treatment of ocular conditions while maintaining good blood glucose control and fundus screening rates.

The Current Understanding of Molecular Mechanisms in Adenomyosis-Associated Infertility and the Treatment Strategy for Assisted Reproductive Technology.

Adenomyosis, endometriosis of the uterus, is associated with an increased likelihood of abnormal endometrial molecular expressions thought to impair implantation and early embryo development, resulting in disrupted fertility, including the local effects of sex steroid and pituitary hormones, immune responses, inflammatory factors, and neuroangiogenic mediators. In the recent literature, all of the proposed pathogenetic mechanisms of adenomyosis reduce endometrial receptivity and alter the adhesion molecule expression necessary for embryo implantation. The evidence so far has shown that adenomyosis causes lower pregnancy and live birth rates, higher miscarriage rates, as well as adverse obstetric and neonatal outcomes. Both pharmaceutical and surgical treatments for adenomyosis seem to have a positive impact on reproductive outcomes, leading to improved pregnancy and live birth rates. In addition, adenomyosis has negative impacts on reproductive outcomes in patients undergoing assisted reproductive technology. This association appears less significant after patients follow a long gonadotropin-releasing hormone agonist (GnRHa) protocol, which improves implantation rates. The pre-treatment of GnRHa can also be beneficial before engaging in natural conception attempts. This review aims to discover adenomyosis-associated infertility and to provide patient-specific treatment options.

Study on Design, Synthesis and Herbicidal Activity of Novel 6-Indazolyl-2-picolinic Acids.

Thirty-eight new 4-amino-3,5-dicholo-6-(1H-indazolyl)-2-picolinic acids and 4-amino-3,5-dicholo-6-(2H-indazolyl)-2-picolinic acids were designed by scaffold hopping and synthesized to discover potential herbicidal molecules. All the new compounds were tested to determine their inhibitory activities against Arabidopsis thaliana and the root growth of five weeds. In general, the synthesized compounds exhibited excellent inhibition properties and showed good inhibitory effects on weed root growth. In particular, compound 5a showed significantly greater root inhibitory activity than picloram in Brassica napus and Abutilon theophrasti Medicus at the concentration of 10 µM. The majority of compounds exhibited a 100% post-emergence herbicidal effect at 250 g/ha against Amaranthus retroflexus and Chenopodium album. We also found that 6-indazolyl-2-picolinic acids could induce the up-regulation of auxin genes ACS7 and NCED3, while auxin influx, efflux and auxin response factor were down-regulated, indicating that 6-indazolyl-2-picolinic acids promoted ethylene release and ABA production to cause plant death in a short period, which is different in mode from other picolinic acids.

Adaptive immune dysfunction in patients with COVID-19 and impaired kidney function during the omicron surge.

BACKGROUND: Little is known about the characteristics of lymphocyte subsets and the association with patient outcomes in COVID-19 with and without impaired kidney function. METHODS: Lymphocyte subsets were compared in COVID-19 patients with or without kidney dysfunction. The primary outcome was a composite of all-cause mortality or intensive care unit admission. Secondary outcomes included duration of viral shedding, length of hospital stay, and acute kidney injury. RESULTS: Lymphocyte subset cell counts demonstrated the lowest in patients with severe/critical COVID-19 and kidney dysfunction. Among all lymphocyte subset parameters, Th cell count was the most significant indicator for outcomes. ROC of the combined model of Th cell count and eGFR presented better predictive value than that of the other parameters. Th cell count <394.5 cells/µl and eGFR <87.5 ml/min/1·73m2 were independently associated with poor outcomes. The propensity score matching analysis revealed consistent results. CONCLUSIONS: Reduced Th cell count and eGFR may be applied as promising predictive indicators for identifying COVID-19 patients with high risk and poor outcomes.

Identification of MYB gene family and functional analysis of GhMYB4 in cotton (Gossypium spp.).

Myeloblastosis (MYB) transcription factors (TFs) form a large gene family involved in a variety of biological processes in plants. Little is known about their roles in the development of cotton pigment glands. In this study, 646 MYB members were identified in Gossypium hirsutum genome and phylogenetic classification was analyzed. Evolution analysis revealed assymetric evolution of GhMYBs during polyploidization and sequence divergence of MYBs in G. hirustum was preferentially happend in D sub-genome. WGCNA (weighted gene co-expression network analysis) showed that four modules had potential relationship with gland development or gossypol biosynthesis in cotton. Eight differentially expressed GhMYB genes were identified by screening transcriptome data of three pairs of glanded and glandless cotton lines. Of these, four were selected as candidate genes for cotton pigment gland formation or gossypol biosynthesis by qRT-PCR assay. Silencing of GH_A11G1361 (GhMYB4) downregulated expression of multiple genes in gossypol biosynthesis pathway, indicating it could be involved in gossypol biosynthesis. The potential protein interaction network suggests that several MYBs may have indirect interaction with GhMYC2-like, a key regulator of pigment gland formation. Our study was the systematic analysis of MYB genes in cotton pigment gland development, providing candidate genes for further study on the roles of cotton MYB genes in pigment gland formation, gossypol biosynthesis and future crop plant improvement.