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Abstract Background The clinical and virological course of patients with coronavirus disease 2019 (COVID-19) are lacking. We aimed to describe the clinical and virological characteristics of COVID-19 patients from 10 designated hospitals in 10 cities of Jiangsu province, China. The factors associated with the clearance of SARS-CoV-2 were investigated. Methods A total of 328 hospitalized patients with COVID-19 were retrospectively recruited. The epidemiological, clinical, laboratory, radiology and treatment data were collected. The associated factors of SARS-CoV-2 clearance were analyzed. Results The median duration of hospitalization was 16.0 days (interquartile range [IQR] 13.0–21.0 days). On multivariate Cox regression analysis, age > 60 years (hazard ratio [HR] 0.643, 95% confidence interval [CI] 0.454–0.911, P = 0.013) was associated with the delayed SARS-CoV-2 clearance, while the atomized inhalation of interferon α-2b could improve the clearance of SARS-CoV-2 (HR, 1.357, 95% CI 1.050–1.755, P = 0.020). Twenty-six (7.9%) patients developed respiratory failure and 4 (1.2%) patients developed ARDS. Twenty (6.1%) patients were admitted to the ICU, while no patient was deceased. Conclusions Our study found that age > 60 years was associated with the delayed SARS-CoV-2 clearance, while treated with atomized inhalation of interferon α-2b could promote the clearance of SARS-CoV-2.

Limited data are available for clinical characteristics of patients with coronavirus disease 2019 (COVID-19) outside Wuhan. This study aimed to describe the clinical characteristics of COVID-19 and identify the risk factors for severe illness of COVID-19 in Jiangsu province, China. Clinical data of hospitalized COVID-19 patients were retrospectively collected in 8 hospitals from 8 cities of Jiangsu province, China. Clinical findings of COVID-19 patients were described and risk factors for severe illness of COVID-19 were analyzed. By Feb 10, 2020, 202 hospitalized patients with COVID-19 were enrolled. The median age of patients was 44.0 years (interquartile range, 33.0-54.0). 55 (27.2%) patients had comorbidities. At the onset of illness, the common symptoms were fever (156 [77.2%]) and cough (120 [59.4%]). 66 (32.7%) patients had lymphopenia. 193 (95.5%) patients had abnormal radiological findings. 11 (5.4%) patients were admitted to the intensive care unit and none of the patients died. 23 (11.4%) patients had severe illness. Severe illness of COVID-19 was independently associated with body mass index (BMI) ≥ 28 kg/m2 (odds ratio [OR], 9.219; 95% confidence interval [CI], 2.731 to 31.126; P

Abstract Background The endosperm serves as the primary source of nutrients for maize (Zea mays L.) kernel embryo development and germination. Positioned at the base of the endosperm, the transfer cells (TCs) of the basal endosperm transfer layer (BETL) generate cell wall ingrowths, which enhance the connectivity between the maternal plant and the developing kernels. These TCs play a crucial role in nutrient transport and defense against pathogens. The molecular mechanism underlying BETL development in maize remains unraveled. Results This study demonstrated that the MYB-related transcription factor ZmMYBR29, exhibited specific expression in the basal cellularized endosperm, as evidenced by in situ hybridization analysis. Utilizing the CRISPR/Cas9 system, we successfully generated a loss-of-function homozygous zmmybr29 mutant, which presented with smaller kernel size. Observation of histological sections revealed abnormal development and disrupted morphology of the cell wall ingrowths in the BETL. The average grain filling rate decreased significantly by 26.7% in zmmybr29 mutant in comparison to the wild type, which impacted the dry matter accumulation within the kernels and ultimately led to a decrease in grain weight. Analysis of RNA-seq data revealed downregulated expression of genes associated with starch synthesis and carbohydrate metabolism in the mutant. Furthermore, transcriptomic profiling identified 23 genes that expressed specifically in BETL, and the majority of these genes exhibited altered expression patterns in zmmybr29 mutant. Conclusions In summary, ZmMYBR29 encodes a MYB-related transcription factor that is expressed specifically in BETL, resulting in the downregulation of genes associated with kernel development. Furthermore, ZmMYBR29 influences kernels weight by affecting the grain filling rate, providing a new perspective for the complementation of the molecular regulatory network in maize endosperm development.

Abstract Aims Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for hematological malignancies. However, viral infections, particularly EBV infection, frequently occur following allo-HSCT and can result in multi-tissue and organ damage. Due to the lack of effective antiviral drugs, these infections can even progress to post-transplant lymphoproliferative disorders (PTLD), thereby impacting the prognosis. In light of this, our objective is to develop a prediction model for EBV infection following allo-HSCT. Methods A total of 466 patients who underwent haploidentical hematopoietic stem cell transplantation (haplo-HSCT) between September 2019 and December 2020 were included in this study. The patients were divided into a development cohort and a validation cohort based on the timing of their transplantation. Our aim was to develop and validate a grading scale using these cohorts to predict the risk of EBV infection within the first year after haplo-HSCT. Additionally, single-cell RNA sequencing (sc-RNAseq) data from the bone marrow of healthy donors were utilized to assess the impact of age on immune cells and viral infection. Results In the multivariate logistic regression model, four predictors were retained: donor age, female-to-male transplant, graft MNC (mononuclear cell) dose, and CD8 dose. Based on these predictors, an EBV reactivation predicting score system was constructed. The scoring system demonstrated good calibration in both the derivation and validation cohorts, as confirmed by the Hosmer–Lemeshow test (p > 0.05). The scoring system also exhibited favorable discriminative ability, as indicated by the C statistics of 0.72 in the derivation cohort and 0.60 in the validation cohort. Furthermore, the clinical efficacy of the scoring system was evaluated using Kaplan–Meier curves based on risk ratings. The results showed significant differences in EBV reactivation rates between different risk groups, with p-values less than 0.001 in both the derivation and validation cohorts, indicating robust clinical utility. The analysis of sc-RNAseq data from the bone marrow of healthy donors revealed that older age had a profound impact on the quantity and quality of immune subsets. Functional enrichment analysis highlighted that older age was associated with a higher risk of infection. Specifically, CD8 + T cells from older individuals showed enrichment in the pathway of “viral carcinogenesis”, while older CD14 + monocytes exhibited enrichment in the pathway of "regulation of viral entry into host cell." These findings suggest that older age may contribute to an increased susceptibility to viral infections, as evidenced by the altered immune profiles observed in the sc-RNAseq data. Conclusion Overall, these results demonstrate the development and validation of an effective scoring system for predicting EBV reactivation after haplo-HSCT, and provide insights into the impact of age on immune subsets and viral infection susceptibility based on sc-RNAseq analysis of healthy donors' bone marrow.

In the realm of genetically transformed crops, the process of plant regeneration holds utmost significance. However, the low regeneration efficiency of several wheat varieties currently restricts the use of genetic transformation for gene functional analysis and improved crop production. This research explores overexpression of TaLAX PANICLE1 (TaLAX1), which markedly enhances regeneration efficiency, thereby boosting genetic transformation and genome editing in wheat. Particularly noteworthy is the substantial increase in regeneration efficiency of common wheat varieties previously regarded as recalcitrant to genetic transformation. Our study shows that increased expression of TaGROWTH-REGULATING FACTOR (TaGRF) genes, alongside that of their co-factor, TaGRF-INTERACTING FACTOR 1 (TaGIF1), enhances cytokinin accumulation and auxin response, which may play pivotal roles in the improved regeneration and transformation of TaLAX1-overexpressing wheat plants. Overexpression of TaLAX1 homologs also significantly increases the regeneration efficiency of maize and soybean, suggesting that both monocot and dicot crops can benefit from this enhancement. Our findings shed light on a gene that enhances wheat genetic transformation and elucidate molecular mechanisms that potentially underlie wheat regeneration.

Gradient refractive index (GRIN) metamaterial lenses can achieve multi-band fusion infrared imaging and has the characteristics of integration, light weight, and achromaticity, compared with existing curved refractive lenses group. Constructing a three-dimensional (3D) GRIN lens for dual-band (3.0–5.0 and 7.5–9.2 µm) mid-infrared imaging is challenging due to the difficulty of fabricating the desired 3D GRIN materials with continuously changing linewidths. Here, we present a 3D self-focusing GRIN lens with a cylindrical symmetry configuration in the mid-infrared band. Such a 3D GRIN lens is designed with gradient woodpile polymer metamaterials based on effective medium theory and fabricated with high fidelity by grayscale two-photon lithography. Simulated and experimental results simultaneously exhibit a 3D GRIN lens possessing dual-band, achromatic, near-diffraction-limit focusing on the wavelengths of 4.5 and 7.5 µm. The protocol for developing the 3D GRIN lens with dual-band fusion imaging would prompt potential applications in integrated light-coupled devices and lightweight infrared imaging devices.

螺杆挤压组织化技术是植物蛋白肉生产加工的主要方式，具有规模化、产业化、连续化、高效节能等优点。旨在对植物蛋白螺杆挤压组织化技术进行梳理，从螺杆挤压组织化技术及其设备方面综述了植物蛋白螺杆挤压组织化技术的研究进展，阐述了螺杆挤压组织化过程的影响因素。螺杆挤出机是植物蛋白挤压组织化加工的主要设备，螺杆为螺杆挤出机的核心部件，螺杆元件及螺杆构型对挤压压力、剪切力、扭矩和平均停留时间具有较大影响。温度、剪切力、压力、原料等都是影响植物蛋白螺杆挤压组织化过程的重要因素。Screw extrusion texturing technology is the main way of vegetable protein meat production, with the advantages of scale, industrialization, continuity, high efficiency and energy saving. To sort out the plant protein screw extrusion texturing technology, the research progress of screw extrusion texturing technology of plant protein was reviewed from the aspects of screw extrusion texturing technology and equipment and the influencing factors of screw extrusion texturing process were elaborated. Screw extruder was the main equipment of plant protein extrusion texturing process with screw as the core component of screw extruder, screw elements and screw configuration had great influence on extrusion pressure, shear force, torque and average residence time. Temperature, shear force, pressure and raw materials were the important factors affecting the plant protein screw extrusion texturing process.

In order to improve the drying rate and rehydration of tilapia meat, the freeze-drying characteristics and quality changes of blanched or steamed fish meat were analyzed. The effect of heat pretreatment on the quality of freeze-dried fish meat was elucidated by considering the denaturation degree of myofibrillar protein, water distribution and microstructural changes in fish meat during the drying process. The results showed that heat pretreatment could effectively improve the drying rate of tilapia meat, shortening the drying time by nine hours compared with the control group; blanching was more effective than steaming. The rehydration temperature range for tilapia meat was expanded by heat pretreatment, and good rehydration was observed at 50–80 ℃. The rehydration temperature for the control samples was 80 ℃, and the rehydration rate of the 10 min heat treatment group was more than 60%, indicating that the dried product can be rapidly rehydrated. The hardness of the rehydrated fish meat was similar to that of cooked fresh fish meat, and it had good mouthfeel. Heat pretreatment caused significant denaturation of myofibrillar protein and consequently changes in water distribution and a conspicuous increase in the peak area of transverse relaxation time T23, indicating that the increase in free water content after heat treatment is an important reason for the increase in freeze-drying rate. The experimental results can provide technical support for the development of ready-to-eat dried fish products that are suitable for rehydration.

Abstract The respiratory system’s complex cellular heterogeneity presents unique challenges to researchers in this field. Although bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) have provided insights into cell types and heterogeneity in the respiratory system, the relevant specific spatial localization and cellular interactions have not been clearly elucidated. Spatial transcriptomics (ST) has filled this gap and has been widely used in respiratory studies. This review focuses on the latest iterative technology of ST in recent years, summarizing how ST can be applied to the physiological and pathological processes of the respiratory system, with emphasis on the lungs. Finally, the current challenges and potential development directions are proposed, including high-throughput full-length transcriptome, integration of multi-omics, temporal and spatial omics, bioinformatics analysis, etc. These viewpoints are expected to advance the study of systematic mechanisms, including respiratory studies.

Abstract ISG15 plays a crucial role in the innate immune response and has been well-studied due to its antiviral activity and regulation of signal transduction, apoptosis, and autophagy. ISG15 is a ubiquitin-like protein that is activated by an E1 enzyme (Uba7) and transferred to a cognate E2 enzyme (UBE2L6) to form a UBE2L6-ISG15 intermediate that functions with E3 ligases that catalyze conjugation of ISG15 to target proteins. Despite its biological importance, the molecular basis by which Uba7 catalyzes ISG15 activation and transfer to UBE2L6 is unknown as there is no available structure of Uba7. Here, we present cryo-EM structures of human Uba7 in complex with UBE2L6, ISG15 adenylate, and ISG15 thioester intermediate that are poised for catalysis of Uba7-UBE2L6-ISG15 thioester transfer. Our structures reveal a unique overall architecture of the complex compared to structures from the ubiquitin conjugation pathway, particularly with respect to the location of ISG15 thioester intermediate. Our structures also illuminate the molecular basis for Uba7 activities and for its exquisite specificity for ISG15 and UBE2L6. Altogether, our structural, biochemical, and human cell-based data provide significant insights into the functions of Uba7, UBE2L6, and ISG15 in cells.

The weathering at the top of bedrock in Jurassic coalfield in northern Shaanxi is strong, and the formed weathered bedrock aquifer is the main water filling source of the mine, which poses a serious threat to the safe mining of the mine. The scientific evaluation of the water abundance of the weathered bedrock aquifer and the advanced drainage of the areas with strong water abundance are essential measures for preventing and controlling water disasters of the roof weathered bedrock. In this paper, taking Nanliang Coal Mine as an example, according to the drilling data, the weathering index, core recovery rate, brittle-plastic rock thickness ratio and rock structure index are selected to construct the evaluation system. The fuzzy analytic hierarchy process and coefficient of variation method are used to weigh comprehensively, and the water abundance of weathered bedrock aquifer in Nanliang Coal Mine is evaluated. The results show that the weathering degree of bedrock in Nanliang Coal Mine is strongly affected by ancient terrain, and the underlying Quaternary gully controls the thickness of the bedrock weathering zone. Combined with the evaluation results of mine water inrush status, the water inflow in the water-rich area is large.

Abstract Despite the importance of English in various aspects of life, students learning English as a foreign language often lack sufficient opportunities to practice speaking in their daily lives. To address these issues, this study proposes an innovative mobile app called Ubiquitous English (UEnglish) that facilitates English speaking learning in authentic contexts anytime and anywhere. Leveraging advanced technologies, UEnglish incorporates automatic speech recognition (ASR), cloud machine translation (MT), and text-to-speech (TTS) functionalities. The primary aim of this study is to assess the impact of UEnglish on students’ English speaking ability, specifically focusing on the quality and quantity of their spoken English when describing comic pictures and authentic pictures. To investigate the learning behaviors and the influence on English speaking learning achievement in this study, 56 fifth-grade students were employed, including 28 students in an experimental group (EG) using UEnglish and 28 students in a control group (CG) with a paper-based teaching method. The results indicated that, after the experiment, EG outperformed CG and EG had significant differences in the quality and quantity of English speaking in the context of describing comic pictures and authentic pictures. Students’ learning portfolios revealed that EG students not only could use more English words and more complex sentences to express their thoughts but also easily applied what they learned when encountering similar contexts. Our findings suggested that authentic contextual English learning with UEnglish was helpful for students to practice speaking English related to their surroundings.

Since the first cloned sheep was produced in 1996, cloning has attracted considerable attention because of its great potential in animal breeding. Somatic cell nuclear transfer (SCNT) is widely used for creating clones. However, SCNT is very complicated to manipulate and inevitably causes intracellular damage during manipulation. Typically, only less than 1% of reconstructed embryos develop into live cloned animals. This low success rate is considered to be the major limitation in the extensive application of cloning techniques. In this study, we proposed an intracellular strain evaluation-based oocyte enucleation method to reduce potential intracellular damage in SCNT. We first calculated the intracellular strain based on the intracellular velocity field and then used the intracellular strain as a criterion to improve the enucleation operation. We then developed a robotic batch SCNT system to apply this micromanipulation method to animal cloning. Experimental results showed that we increased the blastocyst rate from 10.0% to 20.8%, and we successfully produced 17 cloned piglets by robotic SCNT for the first time. The success rate of cloning was significantly increased compared to that of traditional methods (2.50% vs 0.73% on average). In addition to the cloning technique, the intracellular strain evaluation-based enucleation method is expected to be applicable to other biological operations and for establishing a universal cell manipulation protocol to reduce intracellular damage.

In cold regions, the thermal effect of accumulated water on underlying permafrost and permafrost subgrade remains a significant hazard causing engineering risks. Water depth of accumulated water may be an important influence factor of permafrost thermal stability, but there is lack of qualitative and quantitative research about that. In this study, equivalent thermal conductivity theory and solid heat transfer theory have been used to establish the calculation model for simulating heat transfer in water and soil. Thereafter, the accuracy and reliability of the calculation model are checked by monitored data and subsequently used to analyze the thermal erosion of water on underlying permafrost and permafrost under the embankment. These simulation results show that shallow water can protect permafrost and deeper water disrupts the thermal stability of underlying permafrost. The thermal effect extent of water is primarily determined by its depth, and the concept of critical depth and stable depth of accumulated water has been proposed. Moreover, the temperature field of permafrost under embankment can be changed by the slope toe water. In addition, the thermal effect range of the slope toe water is limited by the thermal influence radius, which increases with the depth of standing water. These findings provide support as well as a fundamental base for environmental issues arising from the accumulated water. These observations will, thus, also be valuable to further engineering environment studies in cold regions.

Objective: Dalbergia odorifera has long been used as a Chinese herbal medicine for the treatment of cardiovascular and cerebrovascular diseases. This study aimed to determine the potential myocardial protective effect and possible mechanism of action of D. odorifera essential oil (DOEO). Materials and Methods: The essential oil of D. odorifera was extracted by hydrodistillation. The cardioprotective effects of DOEO were examined by histopathological observation, myocardial enzyme detection, peroxidation, anti-oxidant level detection, and related protein expression. The compounds in the blood were identified by gas chromatography–mass spectrometry. Results: These results showed that DOEO had significant myocardial cell protection, with IC50 values ranging from 17.64 to 24.78 μg/mL in vitro. Compared to the myocardial ischemia group, the DOEO pretreatment groups had lower levels of myocardial injury, creatinine kinase, lactate dehydrogenase, alanine transaminase, aspartate transaminase, hydrogen peroxide, and nitric oxide, and higher levels of glutathione and superoxide dismutase. In addition, DOEO pretreatment significantly increased Na+-K+-ATPase and Ca2+-ATPase levels. Moreover, immunohistochemical experiments showed that DOEO remarkably increased the protein levels of NF-E2-related nuclear factor 2 (Nrf2) and heme oxygenase-1 (HO-1) and reduced the expression of apoptotic caspases, including caspase 3 and caspase 9. The main components of the blood were transnerolidol and nerolidol oxide. Overall, the study showed that DOEO displayed myocardial protection by upregulating the NF-E2-related nuclear factor- antioxidant response element (Nrf2-ARE) and caspase pathways. DOEO has a therapeutic effect on MI by inhibiting the oxidant and apoptotic effects. Conclusions: D. odorifera may be a potential candidate drug for treating myocardial ischemic injury.

The presence of donor-specific antibodies (DSA) are associated with graft failure either following human leukocyte antigen (HLA)-mismatched allogeneic stem cell transplantation or after organ transplantation. Although targeting B cells and plasma cells have been used for desensitization, there have been reports of failure. T-follicular helper (Tfh) cells assist B cells in differentiating into antibody-secreting plasma cells. We used haploidentical allograft as a platform to investigate the possibility of targeting Tfh cells to desensitize DSA. The quantities of circulating Tfh (cTfh) cell subsets in allograft candidates were abnormal, and these cells, including the cTfh2 and cTfhem cell subsets, were positively related to the production of anti-HLA antibodies. Ex vivo experiments showed that the cTfh cells of anti-HLA antibody-positive allograft candidates could induce B cells to differentiate into DSA-producing plasmablasts. The immune synapse could be involved in the assistance of cTfh cells to B cells in antibody production. In vitro experiments and in vivo clinical pilot studies indicated that targeting cTfh cells with sirolimus can inhibit their auxiliary function in assisting B cells. Ex vivo and in vivo studies demonstrated the effect of sirolimus and rituximab on DSA desensitization compared with either sirolimus or rituximab alone (60%, 43.75%, and 30%, respectively). Our findings provide new insight into the role of Tfh cells in the pathogenesis of DSA production in HLA-mismatched transplant candidates. Our data also indicate that targeting Tfh cells is a novel strategy for DSA desensitization and combination of sirolimus and rituximab might be a potential therapy. The prospective cohort of this study is registered at http://www.chictr.org.cn as #ChiCTR-OPC-15006672.

In embryonal rhabdomyosarcoma (ERMS) and generally in sarcomas, the role of wild-type and loss- or gain-of-function TP53 mutations remains largely undefined. Eliminating mutant or restoring wild-type p53 is challenging; nevertheless, understanding p53 variant effects on tumorigenesis remains central to realizing better treatment outcomes. In ERMS, >70% of patients retain wild-type TP53, yet mutations when present are associated with worse prognosis. Employing a kRASG12D-driven ERMS tumor model and tp53 null (tp53-/-) zebrafish, we define wild-type and patient-specific TP53 mutant effects on tumorigenesis. We demonstrate that tp53 is a major suppressor of tumorigenesis, where tp53 loss expands tumor initiation from 97% of animals. Characterizing three patient-specific alleles reveals that TP53C176F partially retains wild-type p53 apoptotic activity that can be exploited, whereas TP53P153Δ and TP53Y220C encode two structurally related proteins with gain-of-function effects that predispose to head musculature ERMS. TP53P153Δ unexpectedly also predisposes to hedgehog-expressing medulloblastomas in the kRASG12D-driven ERMS-model.

Abstract Foggy weather can cause such problems as blurred image information and the loss of image details, which may pose great challenges to road traffic target detection based on images and videos. In this study, we propose a domain‐adaptive road vehicle target detection method to implement domain adaptation for the real foggy scene. We firstly constructed a highway vehicle detection dataset with foggy images (HVFD), which contains normal weather images and foggy images and provides a complete data support for vehicle detection based on computer vision. Secondly, by improving CycleGAN we designed an improved generative confrontation network (CPGAN), which realised the style transfer between foggy images and normal weather images. Finally, we formulated a YOLOv4 target detection framework according to the domain adaptation based on the pre‐trained YOLOv4 fog vehicle detection model. The experimental results show that the method we put forward can effectively improve vehicle detection performance and reduce the work of manually labelling a large number of foggy image tags, which has a strong generalisation ability for computer vision‐based applications in low‐visibility weather.

Abstract The manipulation of surface plasmon polaritons plays a pivotal role in plasmonic science and technology, however, the modulation efficiency of the traditional method suffers from the weak light-matter interaction. Herein, we propose a new method to overcome this obstacle by directly controlling the couple of photon and electron. In this paper, a hybrid graphene-dielectric- interdigital electrode structure is numerically and experimentally investigated. The plasmon is excited due to the confined carrier which is regulated by the potential wells. The frequency of plasmon can be tuned over a range of ~ 33 cm−1, and the obtained maximum extinction ratio is 8% via changing the confined area and the density of carrier. These findings may open up a new path to design the high efficiency all-optical modulator because the electrons can also be driven optically.

BackgroundThe increase in the number of children with global developmental delay and hypotonia is a growing concern. However, clinical rehabilitation for these patients is often carried out using monotherapy approaches, and the period for achieving improvement is relatively long.ObjectiveTo observe the effect of vestibular training with regular rehabilitation on muscle tone and global developmental level in children with global developmental delay with hypotonia, providing evidence for improving treatment options for these children.MethodsSixty children with global developmental delay accompanied by hypotonia who received rehabilitation training in Department of Pediatric Rehabilitation, Rehabilitation Center, the Second Affiliated Hospital of Heilongjiang University of Chinese Medicine from April 2018 to January 2020 were selected, and equally randomized into a control group (regular rehabilitation) and an observation group (vestibular training with regular rehabilitation) . Both groups were treated once daily, 6 days per week, for consecutive 4 weeks. Changes in the normative percentages of Griffiths Mental Development Scales (GMDS) subscales and development quotient, and muscle tone grading of both groups were observed before and after treatment. The overall response rates of muscle tone improvement were compared between the groups.ResultsThe values of normative percentages of GMDS subscales and development quotient were similar in both groups at baseline (P>0.05) , but they were more higher in the observation group after intervention (P0.05) . The observation group had a much higher overall response rate of muscle tone improvement 〔86.7% (26/30) : 17 (56.7%) with significant responses, 9 (30.0%) with fair responses, 4 (13.3%) with no responses〕 than the control group〔56.7% (17/30) : 9 (30.0%) with significant responses, 8 (26.7%) with fair responses, 13 (43.3%) with no responses〕 (χ2=13.658, P

Grain sorghum has been a significant contributor to global food security since the prehistoric period and may contribute even more to the security of both food and energy in the future. Globally, precise management techniques are crucial for increasing grain sorghum productivity. In China, with diverse ecological types, variety introduction occasionally occurs across ecological zones. However, few information is available on the effect of ecological type on genotype performance and how plant spacing configuration influences grain yield in various ecological zones. Hence, a series of two-year field experiments were conducted in 2020 and 2021 in four ecological zones of China, from the northeast to the southwest. The experiments included six widely adapted sorghum varieties under six plant spacing configurations (two row spacing modes: equidistant row spacing (60 cm) mode and wide (80 cm)-narrow (40 cm) row spacing mode; three in-row plant spacings: 10 cm, 15 cm, and 20 cm). Our results indicated that ecological type, variety, and plant spacing configuration had a significant effect on sorghum yield. Ecological type contributed the highest proportion to the yield variance (49.8%), followed by variety (8.3%), while plant spacing configuration contributed 1.8%. Sorghum growth duration was highly influenced by the ecological type, accounting for 87.2% of its total variance, whereas plant height was mainly affected by genotype, which contributed 81.6% of the total variance. All test varieties, developed in the south or north, can reach maturity within 94-108 d, just before fall sowing in central China. Generally, sorghum growth duration becomes longer when a variety is introduced from south to north. A late-maturing variety, developed in the spring sowing and late-maturing regions, possibly could not reach maturity in the early-maturing region. The row spacing modes had no significant affect on sorghum yield, but the equal-row spacing mode consistently caused higher yields with only one exception; this might imply that equal-row spacing mode was more advantageous for boosting sorghum yield potential. In contrast, decreasing in-row plant spacing showed significant positive linear associations with sorghum grain yield in most cases. In addition, these results demonstrated that sorghum is a widely adapted crop and enables success in variety introduction across ecological zones.

The therapy of recurrent hepatocellular carcinoma (RHCC) remains poorly defined. Repeat hepatectomy (RH) and radiofrequency ablation (RFA) have offered as alternative therapy choices. Our study aims to assess survival benefits of RFA versus reresection for RHCC after resection. The electronic databases were used in order to explore the researches analyzing the efficacy of RH vs. RFA in treating RHCC updated to June 2020. After strict evaluation on quality, the interested results were extracted from articles. Totally, a total of 11 publications involving 1515 subjects were included, with 645 conducted RH and 870 taking RHA. We found that RH was associated with better 3-year OS (OR = 1.58, 95% CI = 1.22–2.05, P = 0.0005), while no difference with 1-year (OR = 1.03, 95% CI = 0.07–1.51, P = 0.90) or 5-year OS (OR = 1.66, 95% CI = 0.88–3.14, P = 0.12) in comparison with RFA for RHCC. In terms of DFS, RH was associated with better 3-year DFS (OR = 1.51, 95% CI = 1.11–2.06, P = 0.009) and 5-year DFS (OR = 1.54, 95% CI = 1.14–2.09, P = 0.005) than RFA. Moreover, RH had more morbidity compared with patients who underwent RFA for RHCC patients (OR = 5.61, 95% CI = 3.02–10.42, P

Abstract Graft‐versus‐host disease (GVHD) is a major life‐threatening complication of allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Inflammatory signaling pathways promote T‐cell activation and are involved in the pathogenesis of GVHD. Suppressor of cytokine signaling 1 (SOCS1) is a critical negative regulator for several inflammatory cytokines. However, its regulatory role in T‐cell activation and GVHD has not been elucidated. Multiomics analysis of the transcriptome and chromatin structure of granulocyte‐colony‐stimulating‐factor (G‐CSF)‐administered hyporesponsive T cells from healthy donors reveal that G‐CSF upregulates SOCS1 by reorganizing the chromatin structure around the SOCS1 locus. Parallel in vitro and in vivo analyses demonstrate that SOCS1 is critical for restraining T cell activation. Loss of Socs1 in T cells exacerbates GVHD pathogenesis and diminishes the protective role of G‐CSF in GVHD mouse models. Further analysis shows that SOCS1 inhibits T cell activation not only by inhibiting the colony‐stimulating‐factor 3 receptor (CSF3R)/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway, but also by restraining activation of the inflammasome signaling pathway. Moreover, high expression of SOCS1 in T cells from patients correlates with low acute GVHD occurrence after HSCT. Overall, these findings identify that SOCS1 is critical for inhibiting T cell activation and represents a potential target for the attenuation of GVHD.

Abstract Background Pentatricopeptide repeat (PPR) proteins compose a large protein family whose members are involved in both RNA processing in organelles and plant growth. Previous reports have shown that E-subgroup PPR proteins are involved in RNA editing. However, the additional functions and roles of the E-subgroup PPR proteins are unknown. Results In this study, we developed and identified a new maize kernel mutant with arrested embryo and endosperm development, i.e., defective kernel (dek) 55 (dek55). Genetic and molecular evidence suggested that the defective kernels resulted from a mononucleotide alteration (C to T) at + 449 bp within the open reading frame (ORF) of Zm00001d014471 (hereafter referred to as DEK55). DEK55 encodes an E-subgroup PPR protein within the mitochondria. Molecular analyses showed that the editing percentage of 24 RNA editing sites decreased and that of seven RNA editing sites increased in dek55 kernels, the sites of which were distributed across 14 mitochondrial gene transcripts. Moreover, the splicing efficiency of nad1 introns 1 and 4 and nad4 intron 1 significantly decreased in dek55 compared with the wild type (WT). These results indicate that DEK55 plays a crucial role in RNA editing at multiple sites as well as in the splicing of nad1 and nad4 introns. Mutation in the DEK55 gene led to the dysfunction of mitochondrial complex I. Moreover, yeast two-hybrid assays showed that DEK55 interacts with two multiple organellar RNA-editing factors (MORFs), i.e., ZmMORF1 (Zm00001d049043) and ZmMORF8 (Zm00001d048291). Conclusions Our results demonstrated that a mutation in the DEK55 gene affects the mitochondrial function essential for maize kernel development. Our results also provide novel insight into the molecular functions of E-subgroup PPR proteins involved in plant organellar RNA processing.

Brassica napus cultivars have little or no primary dormancy; however, they are prone to secondary dormancy induction. Secondary dormant seeds can produce volunteer plants, which can result in genetic contamination, reduced quality and biosafety issues. However, information regarding the molecular mechanism underlying secondary dormancy is limited. The MOTHER OF FT AND TFL1 (MFT) gene, which is evolutionarily conserved in the plant kingdom, acts in a complex gene network in the seed dormancy or germination processes. In this study, we identified four B. napus genes that share high homology with AtMFT, named as BnaMFT. Analyses of cis-acting elements showed that BnaMFT promoters contain multiple seed-specific regulatory elements, and various stress- and hormone-responsive elements. Further experiments validated that BnaMFTs were specifically expressed during seed maturation and in the dry seed, with peaks at 35–42 days after pollination. BnaMFTs were not sufficient for primary dormancy; however, they were significantly enhanced by secondary dormancy induction with PEG6000 treatment. Moreover, BnaMFT transcripts were elevated by treatment with abscisic acid (ABA), which is known to be accumulated during secondary dormancy. These results collectively suggest that increased BnaMFT transcription levels are associated with secondary dormancy induction in an ABA-dependent manner in B. napus.

NKG2C+ natural killer (NK) cell plays a vital role in CMV infection control after hematopoietic stem cell transplantation (HSCT). However, the modulation on NKG2C+ NK cell reconstitution is still unclear. NK cell education is affected by the interactions of HLA-I/killer immunoglobulin receptor (KIR). Our aim is to figure out which HLA-I/KIR interaction plays a dominant role in NKG2C+ NK education. Based on allogeneic haploidentical HSCT, we investigated the expansion and function of single KIR positive NKG2C+ NK cells via the interaction of KIR with both donor HLA and recipient HLA at days 30, 90, and 180 after HSCT. KIR2DL2/L3 single-positive/NKG2C+ cells were significantly expanded compared with KIR2DL1 or KIR3DL1 single-positive/NKG2C+ cells when donors and recipients were both HLA-C1/C1 or HLA-C1C1BW4 (p < 0.05), with higher NKp30 expression (p < 0.05). Moreover, the proportion of single KIR positive NK cells increased in both NKG2C+/NKG2A- NK cells and conventional NKG2C-/NKG2A- NK cells over time. We also observed that increased proportion of KIR2DL2/L3 single-positive/NKG2C+ NK cells correlated with higher incidence of acute graft-versus-host disease (aGVHD). Our study allows a better understanding of HLA-I/KIR interaction in the NKG2C+ NK cell education after HSCT.

This study aimed to investigate influence of ultrasonic treatment on physicochemical and antioxidant properties of mung bean protein hydrolysate (MPH). Physicochemical properties of MPH were evaluated by Tricine-SDS-PAGE, particle size distribution, fourier transform infrared spectroscopy (FTIR) and fluorescence spectroscopy, among others. Radicals scavenging activities of ABTS, hydroxyl, superoxide anion, Fe2+ chelating ability and reducing power characterized antioxidant activities of MPH. MPH contained four bands of 25.6, 12.8, 10.6 and 4.9 kDa, in which 4.9 kDa was the most abundant. Ultrasonic treatment increased the contents of aromatic and hydrophobic amino acids in MPH. Ultrasonic treatment decreased the content of α-helix of MPH and increased β-sheet and β-turn compared to MPH. MPH-546 W (ultrasonic treatment 546 W, 20 min) had the lowest average particle size (290.13 nm), zeta potential (-36.37 mV) and surface hydrophobicity (367.95 A.U.). Antioxidant activities of ultrasonicated-MPH increased with the ultrasonic power, achieving the lowest IC50 (mg/mL) of 0.1087 (ABTS), 1.796 (hydroxyl), 1.003 (superoxide anion) and 0.185 (Fe2+ chelating ability) in 546 W power. These results indicated ultrasonic treatment would be a promising method to improve the antioxidant properties of MPH, which would broaden the application scope of MPH as bioactive components in the food industry.

CMV infection remains an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Several investigators have reported that adaptive NKG2C+ NK cells persistently expand during CMV reactivation. In our study, 2 cohorts were enrolled to explore the relationships among the NKG2C genotype, NKG2C+ NK cell reconstitution, and CMV infection. Multivariate analysis showed that donor NKG2C gene deletion was an independent prognostic factor for CMV reactivation and refractory CMV reactivation. Furthermore, adaptive NKG2C+ NK cells’ quantitative and qualitative reconstitution, along with their anti-CMV function after transplantation, was significantly lower in patients grafted with NKG2Cwt/del donor cells than in those grafted with NKG2Cwt/wt donor cells. At day 30 after transplantation, quantitative reconstitution of NKG2C+ NK cells was significantly lower in patients with treatment-refractory CMV reactivation than in patients without CMV reactivation and those with nonrefractory CMV reactivation. In humanized CMV-infected mice, we found that, compared with those from NKG2Cwt/del donors, adaptive NKG2C+ NK cells from NKG2Cwt/wt donors induced earlier and stronger expansion of NKG2C+ NK cells as well as earlier and stronger CMV clearance in vivo. In conclusion, donor NKG2C homozygosity contributes to CMV clearance by promoting the quantitative and qualitative reconstruction of adaptive NKG2C+ NK cells after haploidentical allo-HSCT.

BackgroundThe presence of minimal residual disease (MRD) is an independent risk factor for poor prognosis in patients with acute lymphoblastic leukemia (ALL). Moreover, the role of chimeric antigen receptor T-cell (CAR-T) therapy in patients with MRD is currently unclear.MethodsWe conducted a prospective study to investigate the role of CAR-T therapy in patients with persistent/recurrent MRD-positive ALL in first remission.ResultsA total of 77 patients who had persistent/recurrent MRD were included. Of these patients, 43 were enrolled in the CAR-T group, 20 received chemotherapy as a bridge to allogeneic hematopoietic cell transplantation (allo-HSCT), and 14 patients received intensified chemotherapy. MRD negativity was achieved in 90.7% of the patients after CAR-T infusion. Patients who received CAR-T therapy had a higher 3-year leukemia-free survival (LFS) than patients who did not (77.8% vs. 51.1%, P = 0.033). Furthermore, patients in the CAR-T group had a higher 3-year LFS than those in the chemotherapy bridge-to-allo-HSCT group [77.8% (95% CI, 64.8–90.7%) vs. 68.7% (95% CI, 47.7–89.6%), P = 0.575] and had a significantly higher 3-year LFS than those in the intensified chemotherapy group [77.8% (95% CI, 64.8–90.7%) vs. 28.6% (95% CI, 4.9–52.3%), P = 0.001]. Among the patients who received CAR-T therapy, eight were not bridged to allo-HSCT, and six (75%) remained in remission with a median follow-up of 23.0 months after CAR-T infusion.ConclusionsOur findings show that CAR-T therapy can effectively eliminate MRD and improve survival in patients with a suboptimal MRD response.

Background: Traditional Chinese medicine is promising for managing challenging and complex disorders, including cancer, and in particular, saffron is applied in treating various cancer types. However, its potential therapeutic efficacy and active components in managing squamous cell carcinoma of the head and neck (HNSCC) remain unclear yet. Methods: Using network pharmacology approaches, active ingredients of saffron, their target genes, and HNSCC-related genes were identified. Enrichment analyses were conducted for determining molecular functions and pathways enriched by genes that overlapped between the saffron target gene set and the HNSCC gene set. Among the four known active ingredients of saffron, crocetin was found to have the strongest inhibitory impact on HNSCC, based on the findings of cell viability and migration assays. Therefore, the potential target genes of crocetin in HNSCC cells were examined using molecular docking experiments and were confirmed by qPCR. Results: Four active ingredients of saffron and 184 of their target genes were identified. Further, a total of 34 overlapping saffron-/HNSCC-associated targets related to the four active ingredients were screened, and crocetin was chosen for further investigation because it had the strongest inhibitory effect on HNSCC cells. Molecular docking experiments indicated that ESR1 and CCND1 were the target genes of crocetin. These results were confirmed through qPCR analysis, in which crocetin was found to lower the expression of the ESR1 and CCND1 genes in AMC-HN-8 and FaDu cells. Conclusion: According to our results, crocetin is a primary active anti-cancer component of saffron that may have potential in the development of novel HNSCC-treating medications. However, more thorough molecular research is necessary for confirming these results and elucidating the anti-cancer mechanism underlying saffron. [ABSTRACT FROM AUTHOR]

Identification of reservoir types in deep carbonates has always been a great challenge due to complex logging responses caused by the heterogeneous scale and distribution of storage spaces. Traditional cross-plot analysis and empirical formula methods for identifying reservoir types using geophysical logging data have high uncertainty and low efficiency, which cannot accurately reflect the nonlinear relationship between reservoir types and logging data. Recently, the kernel Fisher discriminant analysis (KFD), a kernel-based machine learning technique, attracts attention in many fields because of its strong nonlinear processing ability. However, the overall performance of KFD model may be limited as a single kernel function cannot simultaneously extrapolate and interpolate well, especially for highly complex data cases. To address this issue, in this study, a mixed kernel Fisher discriminant analysis (MKFD) model was established and applied to identify reservoir types of the deep Sinian carbonates in central Sichuan Basin, China. The MKFD model was trained and tested with 453 datasets from 7 coring wells, utilizing GR, CAL, DEN, AC, CNL and RT logs as input variables. The particle swarm optimization (PSO) was adopted for hyper-parameter optimization of MKFD model. To evaluate the model performance, prediction results of MKFD were compared with those of basic-kernel based KFD, RF and SVM models. Subsequently, the built MKFD model was applied in a blind well test, and a variable importance analysis was conducted. The comparison and blind test results demonstrated that MKFD outperformed traditional KFD, RF and SVM in the identification of reservoir types, which provided higher accuracy and stronger generalization. The MKFD can therefore be a reliable method for identifying reservoir types of deep carbonates. [ABSTRACT FROM AUTHOR]