Evolutionary genomics of climatic adaptation and resilience to climate change in alfalfa.

Given the escalating impact of climate change on agriculture and food security, gaining insights into the evolutionary dynamics of climatic adaptation and uncovering climate-adapted variation can empower the breeding of climate-resilient crops to face future climate change. Alfalfa (Medicago sativa subsp. sativa), the queen of forages, shows remarkable adaptability across diverse global environments, making it an excellent model for investigating species responses to climate change. In this study, we performed population genomic analyses using genome resequencing data from 702 accessions of 24 Medicago species to unravel alfalfa's climatic adaptation and genetic susceptibility to future climate change. We found that interspecific genetic exchange has contributed to the gene pool of alfalfa, particularly enriching defense and stress-response genes. Intersubspecific introgression between M. sativa subsp. falcata (subsp. falcata) and alfalfa not only aids alfalfa's climatic adaptation but also introduces genetic burden. A total of 1671 genes were associated with climatic adaptation, and 5.7% of them were introgressions from subsp. falcata. By integrating climate-associated variants and climate data, we identified populations that are vulnerable to future climate change, particularly in higher latitudes of the Northern Hemisphere. These findings serve as a clarion call for targeted conservation initiatives and breeding efforts. We also identified pre-adaptive populations that demonstrate heightened resilience to climate fluctuations, illuminating a pathway for future breeding strategies. Collectively, this study enhances our understanding about the local adaptation mechanisms of alfalfa and facilitates the breeding of climate-resilient alfalfa cultivars, contributing to effective agricultural strategies for facing future climate change.

Two cases of Kawasaki disease: Clinical characteristics and onset of fever and gastrointestinal symptoms.

BACKGROUND: Kawasaki disease (KD) is a prevalent form of systemic vasculitis that can damage various organs and systems in children. Typical KD is not difficult to diagnose in clinical practice. In recent years, it has been shown that an increasing number of children do not satisfy the diagnostic criteria for typical KD. This condition is known as incomplete KD (IKD). It is challenging to promptly diagnose and treat such children in clinical practice. CASE DESCRIPTION: A 10-year-old girl was admitted to the hospital due to fever and abdominal pain. She presented with shock symptoms. An enhanced abdominal computed tomography scan revealed intestinal pneumatosis, effusion, and gallbladder enlargement, indicating intestinal obstruction. Due to the poor outcome following an emergency laparoscopic cholecystectomy, IKD was suspected. A 3-month-old male pediatric patient was admitted to the hospital due to a fever. Patchy, congestive rashes formed on the patient's body as KD progressed. IKD was suspected based on the clinical signs of fever, rash, and hyperemia of the lips. The two patients were then treated with human immunoglobulin and aspirin treatment. The prognosis for the two children was favorable following prompt treatment. CONCLUSION: Due to the fact that IKD is frequently misdiagnosed, it is vital to (1) improve the patient prognosis for the early identification of children with KD with prolonged fever and anti-infection failure as the initial manifestation and (2) perform timely diagnosis and comprehensive treatment.

The complete reference genome for grapevine (Vitis vinifera L.) genetics and breeding.

Grapevine is one of the most economically important crops worldwide. However, the previous versions of the grapevine reference genome tipically consist of thousands of fragments with missing centromeres and telomeres, limiting the accessibility of the repetitive sequences, the centromeric and telomeric regions, and the study of inheritance of important agronomic traits in these regions. Here, we assembled a telomere-to-telomere (T2T) gap-free reference genome for the cultivar PN40024 using PacBio HiFi long reads. The T2T reference genome (PN_T2T) is 69 Mb longer with 9018 more genes identified than the 12X.v0 version. We annotated 67% repetitive sequences, 19 centromeres and 36 telomeres, and incorporated gene annotations of previous versions into the PN_T2T assembly. We detected a total of 377 gene clusters, which showed associations with complex traits, such as aroma and disease resistance. Even though PN40024 derives from nine generations of selfing, we still found nine genomic hotspots of heterozygous sites associated with biological processes, such as the oxidation-reduction process and protein phosphorylation. The fully annotated complete reference genome therefore constitutes an important resource for grapevine genetic studies and breeding programs.

Development and validation of nomograms predicting overall and cancer-specific survival for non-metastatic primary malignant bone tumor of spine patients.

At present, no study has established a survival prediction model for non-metastatic primary malignant bone tumors of the spine (PMBS) patients. The clinical features and prognostic limitations of PMBS patients still require further exploration. Data on patients with non-metastatic PBMS from 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate regression analysis using Cox, Best-subset and Lasso regression methods was performed to identify the best combination of independent predictors. Then two nomograms were structured based on these factors for overall survival (OS) and cancer-specific survival (CSS). The accuracy and applicability of the nomograms were assessed by area under the curve (AUC) values, calibration curves and decision curve analysis (DCA). Results: The C-index indicated that the nomograms of OS (C-index 0.753) and CSS (C-index 0.812) had good discriminative power. The calibration curve displays a great match between the model's predictions and actual observations. DCA curves show our models for OS (range: 0.09-0.741) and CSS (range: 0.075-0.580) have clinical value within a specific threshold probability range compared with the two extreme cases. Two nomograms and web-based survival calculators based on established clinical characteristics was developed for OS and CSS. These can provide a reference for clinicians to formulate treatment plans for patients.

A population-based nomogram to individualize treatment modality for pancreatic cancer patients underlying surgery.

As the most aggressive tumor, TNM staging does not accurately identify patients with pancreatic cancer who are sensitive to therapy. This study aimed to identify associated risk factors and develop a nomogram to predict survival in pancreatic cancer surgery patients and to select the most appropriate comprehensive treatment regimen. First, the survival difference between radiotherapy and no radiotherapy was calculated based on propensity score matching (PSM). Cox regression was conducted to select the predictors of overall survival (OS). The model was constructed using seven variables: histologic type, grade, T stage, N stage, stage, chemotherapy and radiotherapy. All patients were classified into high- or low-risk groups based on the nomogram. The nomogram model for OS was established and showed good calibration and acceptable discrimination (C-index 0.721). Receiver operating characteristic curve (ROC) and DCA curves showed that nomograms had better predictive performance than TNM stage. Patients were divided into low-risk and high-risk groups according to nomogram scores. Radiotherapy is recommended for high-risk patients but not for low-risk patients. We have established a well-performing nomogram to effectively predict the prognosis of pancreatic cancer patients underlying surgery. The web version of the nomogram https://rockeric.shinyapps.io/DynNomapp/ may contribute to treatment optimization in clinical practice.

Cellulose filter paper immobilized α-glucosidase and its application to screening inhibitors from traditional Chinese medicine.

In this study, α-glucosidase was successfully immobilized on cellulose filter paper and further applied to screening inhibitors from traditional Chinese medicines combined with capillary electrophoresis analysis. For α-glucosidase immobilization, a cellulose filter paper was used as the carrier and grafted with amino groups by coating chitosan, then α-glucosidase was covalently bonded on the amino-modified carrier via epoxy ring-opening reaction using polyethylene glycol diglycidyl ether as the crosslinker. Several parameters influencing the enzyme immobilization were optimized and the optimal values were enzyme concentration of 4 U/mL, polyethylene glycol diglycidyl ether concentration of 1.25%, chitosan concentration of 7.5 mg/mL, immobilization pH 7.0, crosslinking time of 4 h and immobilization time of 2 h. The immobilized α-glucosidase exhibited good batch-to-batch reproducibility (RSD = 2.1%, n = 5), excellent storage stability (73.5% of its initial activity after being stored at 4°C for 15 days), and reusability (75% of its initial activity after 10 repeated cycles). The Michaelis constant of immobilized α-glucosidase and half-maximal inhibitory concentration of acarbose were calculated to be 1.12 mM and 0.38 µM, respectively. Finally, the immobilized α-glucosidase was used for screening inhibitors from 14 kinds of Traditional Chinese Medicine extracts, and Sanguisorbae Radix showed the strongest inhibitory effect on α-glucosidase.

[Wenweishu Capsule alleviates gastric mucosal lesion in rats with chronic gastritis by inhibiting NF-κB pathway].

Objective To investigate the effect of Wenweishu Capsule on the expression of nuclear factor kappa B (NF-κB)-related proteins in chronic gastritis model rats. Methods Wistar rat models of chronic gastritis were constructed by alternant administrations of sodium deoxycholate, ammonia, alcohol solution and the hunger disorder method. The rats were randomly divided into control group, model group, vatacoenayme group, high-, middle- and low-dose Wenweishu Capsule groups. The control group and model group were treated with normal saline (2 mL/d). The other groups were separately treated with 0.3 g/kg vatacoenayme and 0.76, 0.38, 0.19 g/kg Wenweishu Capsule for 4 weeks. Naked eye observation and HE staining were used to evaluate the pathological changes of gastric tissue. ELISA was performed to measure the levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) in the serum. Immunofluorescence staining was employed to observe the expression of NF-κBp65, inhibitor of NF-κBα (IκBα) in the gastric tissue. Simple Western was utilized to detect the protein levels of NF-κBp65, IκBα and COX2 in the gastric tissue. Results Compared with the control group, the model group was found with thinner gastric mucosa, disappeared or shallower folds, obviously infiltrated mucosa inflammatory cells, disordered glands, and significantly increased levels of serum inflammatory cytokines and NF-κBp65, IκBα and COX2 proteins in the gastric tissue. Compared with the model group, the vatacoenayme group, high- and middle-dose Wenweishu Capsule groups showed the alleviated gastric cavity signs, improved histopathological changes, reduced levels of TNF-α and IL-6 in the serum, and decreased expression of NF-κBp65, IκBα and COX2 proteins in the gastric tissue. Conclusion Wenweishu Capsule can reduce the levels of serum inflammatory factors by inhibiting NF-κB pathway in the gastric tissue, so as to alleviate the injury of gastric mucosa in rats with chronic gastritis.

Simultaneous Determination of Dexamethasone, Ondansetron, Granisetron, Tropisetron, and Azasetron in Infusion Samples by HPLC with DAD Detection.

A simple and rapid high-performance liquid chromatography with diode array detector (HPLC-DAD) method has been developed and validated for simultaneous quantification of five antiemetic agents in infusion samples: dexamethasone, ondansetron, granisetron, tropisetron, and azasetron. The chromatographic separation was achieved on a Phenomenex C18 column (4.6 mm × 150 mm, 5 µm) using acetonitrile-50 mM KH2PO4 buffer-triethylamine (25 : 74 : 1; v/v; pH 4.0). Flow rate was 1.0 mL/min with a column temperature of 30°C. Validation of the method was made in terms of specificity, linearity, accuracy, and intra- and interday precision, as well as quantification and detection limits. The developed method can be used in the laboratory to routinely quantify dexamethasone, ondansetron, granisetron, tropisetron, and azasetron simultaneously and to evaluate the physicochemical stability of referred drugs in mixtures for endovenous use.

Living cell intracellular temperature imaging with biocompatible dye-conjugated carbon dots.

Within living cells, the biological functions of subcellular organelles are highly dependent on the distribution of local temperature. In this regard, sensitive and accurate measurement of cellular temperature with subcellular resolution is fundamentally and practically significant. In this work, we demonstrated a fluorescence-based self-calibration method for the quantitative analysis of living cell temperature. A ratiometric temperature sensor was designed by conjugating a temperature sensitive dye, Rhodamine B (RhB), with biocompatible carbon dots (CDs) via a covalent bond. The as-prepared CDs-RhB probe showed excellent ratiometric temperature sensing capability in solution under a single wavelength excitation and displayed a linear temperature sensing range from 5 to 50 °C, which matches the requirement well for the physiologically relevant temperature assay. Furthermore, this probe was applied to map intracellular temperature inside living cells. The fast and accurate temperature response of the probe makes it a promising tool for monitoring the intracellular temperature change, which will promote a better understanding of the temperature relevant biological processes inside living cells.

Physicochemical stability of ternary admixtures of butorphanol, ketamine, and droperidol in polyolefin bags for patient-controlled analgesia use.

BACKGROUND: Delivery of drug admixtures by intravenous patient-controlled analgesia is a common practice for the management of postoperative pain; however, analytical confirmation of the compatibility and stability of butorphanol tartrate, ketamine hydrochloride, and droperidol combined in ternary admixtures is not available. METHODS: Butorphanol tartrate, ketamine hydrochloride, and droperidol have been examined for compatibility and stability when combined with 0.9% sodium chloride injection stored at 4°C and 25°C with light protection for a total of 14 days. Concentrations were 0.067 mg/mL, 1.33 mg/mL, and 0.033 mg/mL for butorphanol tartrate, ketamine hydrochloride, and droperidol, respectively. Drug concentrations were determined using high-performance liquid chromatographic analysis. RESULTS: All three drugs were very stable (>97%) at 4°C and 25°C for 14 days. The ternary admixtures were initially clear and colorless throughout the observation period, and the pH value did not change significantly. CONCLUSION: The results confirm that the ternary admixture of butorphanol tartrate 0.067 mg/mL, ketamine hydrochloride 1.33 mg/mL, and droperidol 0.033 mg/mL in 0.9% sodium chloride injection were stable for 14 days when stored in polyolefin bags at 4°C and 25°C and protected from light.

Incompatibilities of lornoxicam with 4 antiemetic medications in polyolefin bags during simulated intravenous administration.

The administration of drugs by patient-controlled analgesia (PCA) is routinely practiced for the management of postoperative pain. It is common for 2 or more drugs to be combined in PCA solutions. The combination of analgesics and antiemetic agents is frequently required. Unfortunately, the compatibility and stability of lornoxicam and antiemetic agents, such as droperidol, ondansetrone, granisetron, and tropisetron, has not been determined. The aim of this study was to evaluate the compatibility and stability of solutions containing lornoxicam with the 4 antiemetic agents in combination for PCA administration.In our study, test samples were prepared in triplicate by adding 40 mg lornoxicam and 5 mg droperidol, 8 mg ondansetron, 6 mg granisetron, or 5 mg tropisetron to 100-mL polyolefin bags of sodium chloride 0.9% and stored at 25 °C. The analgesic mixture samples were visually inspected for precipitation, cloudiness, and discoloration at each sampling interval. Drug concentrations were determined using high-performance liquid chromatographic (HPLC) analysis.No loss of lornoxicam occurred with any of the 4 antiemetic agents tested for up to 48 hours. However, the contents of droperidol, ondansetron, granisetron, and tropisetron were significant loss >48 hours. After storage of 4.0 to 48.0 hours, the presence of a slight precipitate was observed in all the injection combinations.The results indicate that combinations of lornoxicam with droperidol, ondansetrone, granisetron, or tropisetron in infusion solution during simulated intravenous PCA administration were incompatibility when stored protected from light at 25 °C.

Serum miR-21 level: a potential diagnostic and prognostic biomarker for non-small cell lung cancer.

Because lung cancer is the most common cause of cancer death among both men and women, focused efforts are necessary to identify and develop biomarkers that aid in the detection and treatment of this serious disease. Recent research has been aimed at understanding the roles of microRNAs (miRNAs) in tumorigenesis and their utility as cancer biomarkers. Here, miR-21 was investigated as a potential serum biomarker for non-small cell lung cancer (NSCLC). The relative expression level of miR-21 was detected by real-time PCR in the sera of 80 NSCLC patients; sera were also collected from 60 healthy people as a control. The most suitable cut-off value and the prognostic value of serum miR-21 levels were analyzed using a receiver-operating curve. The relative serum miR-21 level in NSCLC patients was significantly higher than that in healthy people (P<0.05). For relative miR-21 expression, the area under the ROC curve was 0.812 (95% CI: 0.736-0.888) with a sensitivity of 73.8% and a specificity of 71.7%, based on a cut-off value of 1.22. NSCLC patients were divided into two groups based on miR-21 expression; those with higher relative expression (≥1.22) had significantly lower survival time than those in the lower expression group (P<0.05). Further, serum miR-21 level and survival time were negatively correlated in NSCLC patients (P<0.05). Thus, miR-21 may be useful as a diagnostic and prognostic indicator of NSCLC.

Band Structure Engineering and Thermoelectric Properties of Charge-Compensated Filled Skutterudites.

Thermoelectric properties of semiconductors are intimately related to their electronic band structure, which can be engineered via chemical doping. Dopant Ga in the cage-structured skutterudite Co4Sb12 substitutes Sb sites while occupying the void sites. Combining quantitative scanning transmission electron microscopy and first-principles calculations, we show that Ga dual-site occupancy breaks the symmetry of the Sb-Sb network, splits the deep triply-degenerate conduction bands, and drives them downward to the band edge. The charge-compensating nature of the dual occupancy Ga increases overall filling fraction limit. By imparting this unique band structure feature, and judiciously doping the materials by increasing the Yb content, we promote the Fermi level to a point where carriers are in energetic proximity to these features. Increased participation of these heavier bands in electronic transport leads to increased thermopower and effective mass. Further, the localized distortion from Ga/Sb substitution enhances the phonon scattering to reduce the thermal conductivity effectively.

A toll-like receptor 4 (TLR4) variant is associated with asthma severity.

Asthma is a complex airways disease resulting from the input of both biological and environmental factors. Previous studies of single-nucleotide polymorphisms in toll-like receptor 4 (TLR4), which produces a protein involved in regulating T cell populations, have presented conflicting results regarding its role in asthma severity. In the current study, individuals with asthma were genotyped for variants of TLR4, and the genotypes were compared with asthma severity and T cell subpopulations. TLR4 rs11536879 (A>G) and rs1927907 (G>A) genotypes were determined in 350 asthma patients using TaqMan. Asthma severity was graded by clinical symptoms, and blood markers and lung function measures were also collected. T cell subpopulations were identified from peripheral blood by flow cytometry. No significant correlations were observed between genotypes at TLR4 rs11536879 or rs1927907 and eosinophil counts, total serum IgE, serum hypersensitive C-reactive protein, forced expiratory volume in 1 second (FEV1%), or FEV1/forced vital capacity (FVC) in asthma patients (P > 0.05). However, the GG genotype of rs1927907 was correlated with higher asthma severity (P < 0.05). No associations were detected between genotypes at rs11536879 or rs1927907 and CD4(+)CD25(high) regulatory T cell counts in peripheral blood from asthmatic patients (P > 0.05), but the rs1927907 genotype was associated with TLR4 expression on the surface of CD4(+)CD25(high) regulatory T cells (P < 0.05). Therefore, the TLR4 variant rs1927907 appears to be related to asthma severity and TLR4 expression on the surface of CD4(+)CD25(high) regulatory T cells, suggesting the potential influence of TLR4 on T cell population balances.

Stability of butorphanol-tropisetron mixtures in 0.9% sodium chloride injection for patient-controlled analgesia use.

Tropisetron is an adjuvant for butorphanol used in intravenous patient-controlled analgesia (PCA) and has been reported to provide superior pain control. It is efficacious in reducing the incidence of postoperative nausea and vomiting. However, this admixture is not available commercially and stability data applicable to hospital practice are limited. This study aimed to describe the drug compounding and evaluates the long-term (up to 14 days) stability of butorphanol and tropisetron in 0.9% sodium chloride injection for PCA use.In this study, commercial solutions of butorphanol tartrate and tropisetron hydrochloride were combined and further diluted with 0.9% sodium chloride injection to final concentrations of butorphanol tartrate 0.08 mg/mL and tropisetron hydrochloride 0.05 mg/mL. The polyolefin bags and glass bottles were stored at 4°C and 25°C for up to 14 days. The drug stabilities were determined by visual inspection, pH measurement, and high-pressure liquid chromatography assay of drug concentrations.The data obtained for admixtures prepared and stored at temperatures of 25°C and 4°C show the drugs have maintained at least 98% of the initial concentration. All solutions remained clear and colorless over the 14-day period, and the pH value did not change significantly.The results indicate that admixtures of butorphanol tartrate 0.08 mg/mL and tropisetron hydrochloride 0.05 mg/mL in 0.9% sodium chloride injection solution were stable for 14 days when stored in polyolefin bags or glass bottles at 4°C and 25°C and protected from light. The infusion is feasible for manufacturing in pharmacy aseptic units and can be stored for up to 14 days for routine use in PCA infusions.

High current superconductivity in FeSe0.5Te0.5-coated conductors at 30 tesla.

Although high-temperature superconductor cuprates have been discovered for more than 25 years, superconductors for high-field application are still based on low-temperature superconductors, such as Nb(3)Sn. The high anisotropies, brittle textures and high manufacturing costs limit the applicability of the cuprates. Here we demonstrate that the iron superconductors, without most of the drawbacks of the cuprates, have a superior high-field performance over low-temperature superconductors at 4.2 K. With a CeO(2) buffer, critical current densities >10(6) A cm(-2) were observed in iron-chalcogenide FeSe(0.5)Te(0.5) films grown on single-crystalline and coated conductor substrates. These films are capable of carrying critical current densities exceeding 10(5) A cm(-2) under 30 tesla magnetic fields, which are much higher than those of low-temperature superconductors. High critical current densities, low magnetic field anisotropies and relatively strong grain coupling make iron-chalcogenide-coated conductors particularly attractive for high-field applications at liquid helium temperatures.

Stabilizing the optimal carrier concentration for high thermoelectric efficiency.

The band structure of PbTe can be manipulated by alloying with MgTe to control the band degeneracy. This is used to stabilize the optimal carrier concentration, making it less temperature dependent, demonstrating a new strategy to improve overall thermoelectric efficiency over a broad temperature range.

Convergence of electronic bands for high performance bulk thermoelectrics.

Thermoelectric generators, which directly convert heat into electricity, have long been relegated to use in space-based or other niche applications, but are now being actively considered for a variety of practical waste heat recovery systems-such as the conversion of car exhaust heat into electricity. Although these devices can be very reliable and compact, the thermoelectric materials themselves are relatively inefficient: to facilitate widespread application, it will be desirable to identify or develop materials that have an intensive thermoelectric materials figure of merit, zT, above 1.5 (ref. 1). Many different concepts have been used in the search for new materials with high thermoelectric efficiency, such as the use of nanostructuring to reduce phonon thermal conductivity, which has led to the investigation of a variety of complex material systems. In this vein, it is well known that a high valley degeneracy (typically ≤6 for known thermoelectrics) in the electronic bands is conducive to high zT, and this in turn has stimulated attempts to engineer such degeneracy by adopting low-dimensional nanostructures. Here we demonstrate that it is possible to direct the convergence of many valleys in a bulk material by tuning the doping and composition. By this route, we achieve a convergence of at least 12 valleys in doped PbTe(1-x)Se(x) alloys, leading to an extraordinary zT value of 1.8 at about 850 kelvin. Band engineering to converge the valence (or conduction) bands to achieve high valley degeneracy should be a general strategy in the search for and improvement of bulk thermoelectric materials, because it simultaneously leads to a high Seebeck coefficient and high electrical conductivity.