Search

Abstract The nucleolus, a recognized biomolecular condensate, serves as the hub for ribosome biogenesis within the cell nucleus. Its quantity and morphology are discernible indicators of cellular functional states. However, precise identification and quantification of nucleoli remain challenging without specific labeling, particularly for suspended cells, tissue-level analysis and high-throughput applications. Here we introduce a single-cell laser emitting cytometry (SLEC) for label-free nucleolus differentiation through light-matter interactions within a Fabry–Perot resonator. The separated gain medium enhances the threshold difference by 36-fold between nucleolus and its surroundings, enabling selective laser emissions at nucleolar area while maintaining lower-order mode. The laser emission image provides insights into structural inhomogeneity, temporal fluid-like dynamics, and pathological application. Lasing spectral fingerprint depicts the quantity and size of nucleoli within a single cell, showcasing the label-free flow cytometry for nucleolus. This approach holds promise for nucleolus-guided cell screening and drug evaluation, advancing the study of diseases such as cancer and neurodegenerative disorders.

Abstract This study focuses on the ancient bricks of Wei-Jin tombs in Jiayuguan, Gansu, China, analyzing the deterioration of the bricks under the long-term influence of natural environments and human activities. Currently, the ancient bricks exhibit various degradation diseases such as cracks, exfoliation, fracture, weathering, and microbial erosion, severely affecting the integrity of the cultural relics. Through on-site investigation and characterization testing, the physical and mechanical properties, compositional elements, pore size distribution, and thermal characteristics of the ancient bricks were analyzed. Indoor simulation experiments were conducted to study the impact of different types of environmental erosion cycles (such as H2O, HCl, NaOH, Na2SO4) on the performance and structure of the ancient bricks, the patterns and causes of deterioration were also studied. The results indicate that the cyclic effects gradually transform the porosity of the ancient bricks into lateral microcracks, which continue to expand, leading to varying degrees of degradation of performance. The extent of the impact of these cycles on the properties of ancient bricks is in descending order: Na2SO4, HCl, NaOH, H2O. H2O, NaOH, HCl, Na2SO4.

The management of landfill leachate presents a significant environmental challenge, necessitating a comprehensive and dynamic treatment approach. This comprehensive review delves into the critical issue of landfill leachate treatment, exploring its environmental impact, treatment technologies, regulatory frameworks, and the path towards sustainable management practices. This review explores the complexities of landfill leachate, emphasizing the need for sustainable waste management practices to safeguard environmental health. Our analysis highlights the evolution of conventional and advanced treatment technologies designed to mitigate these risks, focusing on membrane technologies, advanced oxidation processes, and the promising potential of emerging techniques such as adsorption and biological nutrient removal. These technologies are evaluated for their efficiency, cost implications, and sustainability impacts, underscoring the challenges and opportunities within the current landscape of leachate treatment. The review aims to provide insights into designing efficient and effective treatment systems through a detailed analysis of conventional and advanced treatment methods. By examining a case study in Changsha City, the effectiveness of a comprehensive treatment system integrating various technologies is demonstrated. The review underscores the interconnectedness of human activities, environmental health, and waste management, emphasizing the importance of a holistic approach. It stresses the continuous improvement of leachate treatment technologies and the adoption of sustainable practices to reduce the environmental footprint of landfills. Ultimately, it calls for integrating multiple treatment processes, economic considerations, and readiness to address future challenges in landfill leachate treatment, contributing to the advancement of sustainable waste management practices.

However, it is still difficult for clinicians to establish prognostic stratifications and therapeutic strategies because of the lack of tools for predicting the survival of triple-negative breast cancer patients with liver metastases (TNBC-LM). Based on clinical data from large populations, a sensitive and discriminative nomogram was developed and validated to predict the prognosis of TNBC patients with LM at initial diagnosis or at the later course. Introduction/background: Liver metastasis (LM) in TNBC patients is associated with significant morbidity and mortality. The objective of this study was to construct a clinical model to predict the survival of TNBC-LM patients. Materials and methods: Clinicopathologic data were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and the Fifth Affiliated Hospital of Sun Yat-Sen University (FAFSYU). Based on patients with newly diagnosed TNBC with LM (nTNBC-LM) from the SEER database, a predictive nomogram was established and validated. Its predictive effect on TNBC patients with LM at later disease course by enrolling TNBC patients from FAFSYU who developed LM later. The prognostic effect of different treatment for nTNBC-LM was further assessed. Results: A prognostic model was developed and validated to predict the prognosis of TNBC-LM patients. For LM patients diagnosed at the initial or later treatment stage, the C-index (0.712, 0.803 and 0.699 in the training, validation and extended groups, respectively) and calibration plots showed the acceptable prognostic accuracy and clinical applicability of the nomogram. Surgical resection on the primary tumour and chemotherapy were found to be associated with significantly better overall survival (OS). Conclusion: A sensitive and discriminative model was developed to predict OS in TNBC-LM patients both at and after initial diagnosis.

A ground-based microwave radiometer (MWR) provides continuous atmospheric profiles under various weather conditions. The change in total precipitable water vapor (PWV) and liquid water path (LWP) before rainfall events is particularly important for the improvement in the rainfall forecast. However, the analysis of the PWV and LWP before rainfall event on the plateau is especially worth exploring. In this study, the MWR installed at Xining, a city located over the northeastern Tibetan Plateau, was employed during September 2021 to August 2022. The results reveal that the MWR-retrieved temperature and vapor density demonstrate reliable accuracy, when compared with radiosonde observations; PWV and LWP values during the summer account for over 70% of the annual totals in the Xining area; both PWV and LWP at the initiating time of rainfall events are higher during summer, especially after sunset (during 20-00 local solar time); and notably, PWV and LWP anomalies are enhanced abruptly 8 and 28 min prior to the initiating time, respectively. Furthermore, the mean of LWP anomaly rises after the turning time (the moment rises abruptly) to the initiating time; as the intensity of rainfall events increases, the occurrence of the turning time is delayed, especially for PWV anomalies; while the occurrence of the turning time is similar for both convective cloud and stratiform cloud rainfall events, the PWV and LWP anomalies jump more the initiating time; as the intensity of rainfall events increases, the occurrence of the turning time is delayed, especially for PWV anomalies; while the occurrence of the turning time is similar for both convective cloud and stratiform cloud rainfall events, the PWV and LWP anomalies jump more dramatically after the turning time in convective cloud events. This study aims are to analyze the temporal characteristics of PWV and LWP, and assess their potential in predicting rainfall event.

The hazard of ice accretion on overhead power circuits is significant, yet predicting it is very difficult. The key reason lies in the shortage of sufficient observational data on ice thickness, and previous studies have also rarely taken into account micro-terrain and micro-meteorological conditions. In response to the challenge of simulating overhead line icing, this study introduces a new icing simulation technique that fully considers the effects of micro-terrain and micro-meteorology. For this technique, typical micro-terrains of overhead line areas are first identified by using high-resolution elevation data, and the icing thickness characteristics in different micro-terrains are analyzed. Subsequently, icing thickness simulations for different micro-terrains are conducted. The results indicate that during the icing process, the icing thickness ranges from 5 mm to 8 mm under three types of micro-terrain, namely, “uplift type”, “alpine drainage divide type” and “canyon wind channel type”, whereas the icing thickness is less than 5 mm in the “flat type” of micro-terrain. This finding suggests that the first three micro-terrain types facilitate icing on overhead transmission lines due to the condensation and uplifting effects of water vapor caused by terrain. However, flat terrain lacks the conditions necessary for water vapor accumulation and thus is not easy to form icing. The results are advantageous for the deployment of overhead power lines in intricate terrain. It is advisable to steer clear of regions susceptible to icing, and endeavor to install circuits in level territories whenever feasible. In addition, the simulated icing thickness under different terrains is in good agreement with the observations. Specifically, the correlation coefficient between simulated and observed icing thickness is significant at the 0.99 confidence level, and the deviations between them are within 0.5 mm. This signifies that the forecasting methodologies employed are dependable and possess significant implications as a reference for disaster prevention and mitigation efforts.

Abstract Sarpagine alkaloids offer signicant opportunities in drug discovery, yet the efficient total syntheses and diverse structural modifications of these natural products remain highly challenging due to the architectural complexity. Here we show a homo-Mannich reaction of cyclopropanol with imines generated via a Bischler-Napieralski reaction enables a protecting-group-free, redox economic, four-step access to the tetracyclic sarpagine core from L-tryptophan esters. Based on this advancement, diversified syntheses of sarpagine alkaloids and analogues are achieved in a short synthetic route. The systematic anticancer evaluation indicates that natural products vellosimine and N a-methyl vellosimine possess modest anticancer activity. Intensive structural optimization of these lead molecules and exploration of the structure−activity relationship lead to the identification of analogue 15ai with an allene unit showing a tenfold improvement in anticancer activities. Further mechanism studies indicate compound 15ai exertes antiproliferation effects by inducing ferroptosis, which is an appealing non-apoptotic cell death form that may provide new solutions in future cancer therapies.

Objective To investigate the effect of evidence-based nursing combined with individualized health education intervention on knowledge about deep vein thrombosis (DVT), self-management ability and discharge readiness of patients with gynecological surgery. Methods A total of 160 patients who underwent gynecological surgery in the hospital from January 2021 to December 2021 were selected as the research subjects. According to different health education methods, they were divided into control group and observation group, 80 cases in each group. The control group received routine health education, and the observation group received evidence-based nursing combined with personalized health education. The self-management ability ［self-care ability measurement scale (ESCA)］, DVT related knowledge (self-made DVT-related knowledge questionnaire), incidence of DVT and discharge readiness level ［Discharge Readiness Assessment Scale (RHDS)］ were compared between the two groups. Results After intervention, the total score and dimensional scores of ESCA in the two groups were increased (P

Objective: To explore the clinical value of whole-body 18F-FDG PET/CT combined with neuroantibody detection in the diagnosis and treatment of paraneoplastic neurological syndromes (PNS). Methods: Clinical, laboratory, and imaging data of 56 hospitalized patients with suspected PNS who underwent systemic 18F-FDG PET/CT and neuropathic tumor antibody detection were retrospectively collected and followed-up on. ROC curve analysis was performed to compare the diagnostic efficacy of PET/CT, neuronal antibodies, and their combined detection results. Results: Among the 56 patients with suspected PNS, there were 20 with malignant tumors, including 19 cases complicated with PNS and 1 patient with spinal cord metastasis which also le d to neurological symptoms. 18F-FDG PET/CT imaging indicated tumors or possible tumors in 23 cases, of which 20 cases were true positive, 3 cases were false positive (the follow-up results were reflux esophagitis, reactive bone changes, or inflammatory lesions in the neck), and the remaining 33 cases were true negative. The sensitivity, specificity, and accuracy of PET/CT were 100%, 91.7%, and 94.6%, respectively. There were 33 cases with positive neuroantibodies, including 8 cases of tumors with PNS (3 cases with anti-amphiphysin antibody encephalitis, 2 cases with anti-GABAb antibody encephalitis, 1 case with anti-Yo antibody encephalitis, and 2 cases with anti-Hu antibody encephalitis). Moreover, there were 25 cases without tumors (10 cases with LGI1 antibody encephalitis, 3 cases with anti-amphiphysin antibody encephalitis, 1 case with anti-Hu antibody encephalitis, 3 cases with anti-GABAb antibody encephalitis, 3 cases with anti-Yo antibody encephalitis, 1 case with Anti-caspr2, 1 case with GAD65, 1 case with NMDA, 1 case with PNMA, and 1 case with SOX1 antibody (1 case each). Of these, 23 cases were negative (12 cases with tumor). The sensitivity, specificity, and accuracy of the neuronal antibody test were 40.0%, 30.6%, and 33.9%, respectively. Furthermore, the sensitivity, specificity, and accuracy of the combined detection were 100.0%, 33.3%, 57.1%, 50%, 94.4%, and 78.6%, respectively. ROC analysis showed that the AUC was 0.958 (P=0.0000.05; 95% CI 0.199~0.506), 0.667 (P=0.040

Abstract Parental genes may indirectly influence offspring psychiatric outcomes through the environment that parents create for their children. These indirect genetic effects, also known as genetic nurture, could explain individual differences in common internalising and externalising psychiatric symptoms during childhood. Advanced statistical genetic methods leverage data from families to estimate the overall contribution of parental genetic nurture effects. This study included up to 10,499 children, 5990 mother–child pairs, and 6,222 father–child pairs from the Norwegian Mother Father and Child Study. Genome-based restricted maximum likelihood (GREML) models were applied using software packages GCTA and M-GCTA to estimate variance in maternally reported depressive, disruptive, and attention-deficit hyperactivity disorder (ADHD) symptoms in 8-year-olds that was explained by direct offspring genetic effects and maternal or paternal genetic nurture. There was no strong evidence of genetic nurture in this sample, although a suggestive paternal genetic nurture effect on offspring depressive symptoms (variance explained (V) = 0.098, standard error (SE) = 0.057) and a suggestive maternal genetic nurture effect on ADHD symptoms (V = 0.084, SE = 0.058) was observed. The results indicate that parental genetic nurture effects could be of some relevance in explaining individual differences in childhood psychiatric symptoms. However, robustly estimating their contribution is a challenge for researchers given the current paucity of large-scale samples of genotyped families with information on childhood psychiatric outcomes.

Most genetic studies of glucose levels have been done on fasting samples, which can be difficult to obtain. Here, the authors identify 156 genetic loci controlling the physiological variation of glucose levels in healthy non-fasting individuals, demonstrating that the results non-fasting samples can be used to predict fasting glucose levels.

Background: Matrilin-2 is a key extracellular matrix protein involved in peripheral nerve regeneration. We sought to develop a biomimetic scaffold to enhance peripheral nerve regeneration by incorporating matrilin-2 within a chitosan-derived porous scaffold. We hypothesized that the use of such a novel biomaterial delivers microenvironmental cues to facilitate Schwann cell (SC) migration and enhance axonal outgrowth during peripheral nerve regeneration.Materials and Methods: The effect of matrilin-2 on SC migration was evaluated with agarose drop migration assay on matrilin-2 coated dishes. SC adhesion was determined with SCs cultured atop tissue culture dishes coated with matrilin-2. Various formulations of chitosan vs matrilin-2 in scaffold constructs were examined with scanning electron microscopy. The effect of the matrilin-2/chitosan scaffold on SC migration in the collagen conduits was determined by capillary migration assays. Neuronal adhesion and axonal outgrowth were evaluated with three-dimensional (3D) organotypic assay of dorsal root ganglions (DRG). DRG axonal outgrowth within the scaffolds was determined by immunofluorescence staining of neurofilaments.Results: Matrilin-2 induced SC migration and enhanced its adhesion. A formulation of 2% chitosan with matrilin-2 demonstrated an optimal 3D porous architecture for SC interaction. Matrilin-2/chitosan scaffold enabled SCs to migrate against gravity within conduits. Chemical modification of chitosan with lysine (K-chitosan) further improved DRG adhesion and axonal outgrowth than the matrilin-2/chitosan scaffold without lysine modification.Conclusion: We developed a matrilin-2/K-chitosan scaffold to mimic extracellular matrix cues and provide a porous matrix to enhance peripheral nerve regeneration. Taking advantage of matrilin-2’s capability to stimulate SC migration and adhesion, we formulated a porous matrilin-2/chitosan scaffold to support axongal outgrowth. Chemical modification of chitosan with lysine further improved matrilin-2 bioactivity in the 3D scaffold. The 3D porous matrilin-2/K-chitosan scaffolds have high potential for enhancing nerve repair by stimulating SC migration, neuronal adhesion, and axonal outgrowth.

The total viable count (TVC) of bacteria is an important index to evaluate the freshness and safety of dishes. To improve the accuracy and robustness of spectroscopic detection of total viable bacteria count in a complex system, a new method based on a near-infrared (NIR) hyperspectral hybrid model and Support Vector Machine (SVM) algorithms was developed to directly determine the total viable count in intact beef dish samples in this study. Diffuse reflectance data of intact and crushed samples were tested by NIR hyperspectral and processed using Multiplicative Scattering Correction (MSC) and Competitive Adaptive Reweighted Sampling (CARS). Kennard–Stone (KS) and Samples Set Partitioning Based on Joint X-Y Distance (SPXY) algorithms were used to select the optimal number of standard samples transferred by the model combined with root mean square error. The crushed samples were transferred into the complete samples prediction model through the Direct Standardization (DS) algorithm. The spectral hybrid model of crushed samples and full samples was established. The results showed that the Determination Coefficient of Calibration (RP2) value of the total samples prediction set increased from 0.5088 to 0.8068, and the value of the Root Mean Square Error of Prediction (RMSEP) decreased from 0.2454 to 0.1691 log10 CFU/g. After establishing the hybrid model, the RMSEP value decreased by 9.23% more than before, and the values of Relative Percent Deviation (RPD) and Reaction Error Relation (RER) increased by 12.12% and 10.09, respectively. The results of this study showed that TVC instewed beef samples can be non-destructively determined based on the DS model transfer method combined with the hybrid model strategy. This study provided a reference for solving the problem of poor accuracy and reliability of prediction models in heterogeneous samples.

As one of the world’s top three popular non-alcoholic beverages, tea is economically and culturally valuable. Xinyang Maojian, this elegant green tea, is one of the top ten famous tea in China and has gained prominence for thousands of years. However, the cultivation history of Xinyang Maojian tea population and selection signals of differentiation from the other major variety Camellia sinensis var. assamica (CSA) remain unclear. We newly generated 94 Camellia sinensis (C. sinensis) transcriptomes including 59 samples in the Xinyang area and 35 samples collected from 13 other major tea planting provinces in China. Comparing the very low resolution of phylogeny inferred from 1785 low-copy nuclear genes with 94 C. sinensis samples, we successfully resolved the phylogeny of C. sinensis samples by 99,115 high-quality SNPs from the coding region. The sources of tea planted in the Xinyang area were extensive and complex. Specifically, Shihe District and Gushi County were the two earliest tea planting areas in Xinyang, reflecting a long history of tea planting. Furthermore, we identified numerous selection sweeps during the differentiation of CSA and CSS and these positive selection genes are involved in many aspects such as regulation of secondary metabolites synthesis, amino acid metabolism, photosynthesis, etc. Numerous specific selective sweeps of modern cultivars were annotated with functions in various different aspects, indicating the CSS and CSA populations possibly underwent independent specific domestication processes. Our study indicated that transcriptome-based SNP-calling is an efficient and cost-effective method in untangling intraspecific phylogenetic relationships. This study provides a significant understanding of the cultivation history of the famous Chinese tea Xinyang Maojian and unravels the genetic basis of physiological and ecological differences between the two major tea subspecies.

Summary: Fungi cause various forms of invasive fungal disease (IFD), and fungal sensitization can contribute to the development of asthma, asthma severity, and other hypersensitivity diseases, such as atopic dermatitis (AD). In this study, we introduce a facile and controllable approach, using homobifunctional imidoester-modified zinc nano-spindle (HINS), for attenuating hyphae growth of fungi and reducing the hypersensitivity response complications in fungi-infected mice. To extend the study of the specificity and immune mechanisms, we used HINS-cultured Aspergillus extract (HI-AsE) and common agar-cultured Aspergillus extract (Con-AsE) as the refined mouse models. HINS composites within the safe concentration range inhibited the hyphae growth of fungi but also reduce the number of fungal pathogens. Through the evaluation of lung and skin tissues from the mice, asthma pathogenesis (lung) and the hypersensitivity response (skin) to invasive aspergillosis were least severe in HI-AsE-infected mice. Therefore, HINS composites attenuate asthma and the hypersensitivity response to invasive aspergillosis.

The musculoskeletal system (MSKS) is composed of specialized connective tissues including bone, muscle, cartilage, tendon, ligament, and their subtypes. The primary function of the MSKS is to provide protection, structure, mobility, and mechanical properties to the body. In the process of fulfilling these functions, the MSKS is subject to wear and tear during aging and after injury and requires subsequent repair. MSKS diseases are a growing burden due to the increasing population age. The World Health Organization estimates that 1.71 billon people suffer from MSKS diseases worldwide. MSKS diseases usually involve various dysfunctions in bones, muscles, and joints, which often result in pain, disability, and a decrease in quality of life. The most common MSKS diseases are osteoporosis (loss of bone), osteoarthritis (loss of cartilage), and sarcopenia (loss of skeletal muscle). Because of the disease burden and the need for treatment, regenerative drug therapies for MSKS disorders are increasingly in demand. However, the difficulty of effective drug delivery in the MSKS has become a bottleneck for developing MSKS therapeutics. The abundance of extracellular matrix and its small pore size in the MSKS present a formidable barrier to drug delivery. Differences of vascularity among various MSKS tissues pose complications for drug delivery. Novel strategies are necessary to achieve successful drug delivery in different tissues composing the MSKS. Those considerations include the route of administration, mechanics of surrounding fluids, and biomolecular interactions, such as the size and charge of the particles and targeting motifs. This review focuses on recent advances in challenges to deliver drugs to each tissue of the MSKS, current strategies of drug delivery, and future ideas of how to overcome drug delivery challenges in the MSKS.

Abstract As the second wave of COVID-19 hits South Asia, an increasing deadly complication ‘fungal infections (such as Mycosis, Candida and Aspergillus) outbreak’ has been raised concern about the insufficient technologies and medicals for its diagnosis and therapy. Biosilica based nano-therapy can be used for therapeutic efficacy, yet their direct role as antibiotic agent with biocompatibility and stability remains unclear. Here, we report that a diatomaceous earth (DE) framework semiconductor composite conjugated DE and in-house synthesized zinc oxide (DE-ZnO), as an antibiotic agent for the enhancement of antibiotic efficacy and persistence. We found that the DE-ZnO composite had enhanced antibiotic activity against fungi (A. fumigatus) and Gram-negative bacteria (E. coli, S. enterica). The DE-ZnO composite provides enhancing large surface areas for enhancement of target pathogen binding affinity, as well as produces active ions including reactive oxygen species and metal ion for breaking the cellular network of fungi and Gram-negative bacteria. Additionally, the toxicity of DE-ZnO with 3 time less amount of dosage is 6 times lower than the commercial SiO2-ZnO. Finally, a synergistic effect of DE-ZnO and existing antifungal agents (Itraconazole and Amphotericin B) showed a better antifungal activity, which could be reduced the side effects due to the antifungal agents overdose, than a single antibiotic agent use. We envision that this DE-ZnO composite can be used to enhance antibiotic activity and its persistence, with less-toxicity, biocompatibility and high stability against fungi and Gram-negative bacteria which could be a valuable candidate in medical science and industrial engineering.

BackgroundIn breast cancer patients with HER2-negative tumors (tHER2-), HER2-positive CTCs (cHER2+) were associated with promising efficacy of HER2-targeted therapy, but controversy has persisted over its prognostic effect. We developed a model including clinicopathologic parameters/blood test variables to predict cHER2 status and evaluated the prognostic value of cHER2+ in tHER2- patients.MethodscHER2+ was detected, blood test results and clinicopathological characteristics were combined, and a nomogram was constructed to predict cHER2 status in tHER2- patients according to logistic regression analysis. The nomogram was evaluated by C-index values and calibration curve. Kaplan–Meier curves, log-rank tests, and Cox regression analyses were performed to evaluate the prognostic value of cHER2 status.ResultsTNM stage, white blood cells (WBCs), neutrophils (NEUs), uric acid (UA), De Ritis ratio [aspartate transaminase (AST)/alanine transaminase (ALT)], and high-density lipoprotein (HDL) were found to be associated with cHER2 status in tHER2- patients in univariate logistic regression analysis, in which UA and De Ritis ratio remained significant in multivariate logistic regression analysis. A model combining these six variables was constructed, the C-index was 0.745 (95% CI: 0.630–0.860), and the calibration curve presented a perfect predictive consistency. In survival analysis, patients of the subgroups “with cHER2+/UA-low” (p = 0.015) and “with cHER2+/De Ritis ratio – high” (p = 0.006) had a significantly decreased disease-free survival (DFS).ConclusionsOur nomogram, based on TNM stage, WBC, NEU, UA, De Ritis ratio, and HDL, may excellently predict the cHER2 status of tHER2- patients. Incorporation with UA and De Ritis ratio may enhance the prognostic value of cHER2 status.

ObjectiveThis study characterizes glucose metabolism and tau protein deposition distribution in patients with Alzheimer’s disease (AD) and to evaluate the relationships between neuropsychological performance and tau protein deposition or glucose metabolism using 18F-FDG and 18F-AV1451 positron emission tomography/computed tomography (PET/CT).MethodsSixty-four patients with β-amyloid-positive (Aβ+) AD and twenty-five healthy participants were enrolled in this study. All participants underwent 18F-FDG and 18F-AV1451 PET/CT. Clinical data and neuropsychological scores were collected. Patients with AD were divided into mild, moderate, and severe groups according to mini-mental state examination (MMSE) scores. The standardized uptake value ratios (SUVRs) for both FDG and AV1451 PET images were calculated using the cerebellar vermis as reference. The SUVRs of the whole cerebral cortex and each brain region were calculated. The volume of interest (VOI) was obtained using automated anatomical atlas (AAL) and Brodmann regions. Student’s t-test was used to perform intergroup comparisons of SUVR. The partial correlation coefficient between SUVR and neuropsychological scores was computed in an inter-subject manner using age and education as covariates.ResultsThe mild subgroup showed a reduction in glucose metabolism and aggregation of tau protein in the temporoparietal cortex. With a decline in neuropsychiatric performance, the SUVR on FDG PET decreased and SUVR on tau PET increased gradually. The areas of glucose metabolism reduction and tau protein deposition appeared first in the parietal cortex, followed by the temporal and frontal cortex, successively. Both FDG and tau SUVRs significantly correlated with MMSE, Montreal cognitive assessment (MOCA), auditory verbal learning test (AVLT), Boston naming test (BNT), clock drawing task (CDT), and verbal fluency test (VFT) (p < 0.05). The SUVR on FDG PET significantly correlated with activities of daily living (ADL) and the Hamilton depression scale (HAMD). There was no significant correlation between the tau SUVRs and ADL or HAMD.ConclusionThe extension of tau protein deposition was similar but not exactly consistent with the area of glucose metabolism reduction. Both tau and FDG SUVRs correlated with cognitive function in domain-specific patterns, and the results of FDG PET more closely correlated with neuropsychological function than tau PET results did.

This study aims to evaluate the performances of two latest released global precipitation measurement (GPM)-era satellite precipitation final run products (integrated merged multisatellite retrievals IMERG-V06B and Global Satellite Mapping of Precipitation GSMaP-V07) and one tropical rainfall measuring mission (TRMM)-era product (TMPA-3B42-V07) at hourly, daily, and monthly scale over the Tibetan plateau (TP), with special focus on the performances at different rain intensities, subbasins, and elevations at daily scales. Besides, hourly scale evaluations were carried out for one grid box value of IMERG-V06B and GSMaP-V07 versus 15 rain gauges on the rainy season, 2019. Results indicated that: First, GSMaP-V07 outperformed TMPA-3B42-V07 and IMERG-V06B with higher correlation coefficient and lower relative bias, mean absolute error, and root-mean-squared error values at daily and monthly scale. Second, satellite products showed overestimation during light rain and underestimation throughout moderate rain, heavy rain, and rainstorm; Third, satellite products have performed relatively better in lower elevation (4000 m). Fourth, satellite precipitation products performed better in the source region of the Yellow River, Yangtze River, Lancang River, and Nujiang River basins, whereas the products greatly overestimated the precipitation in the source region of the Yarlung zangbo River basin. In arid climate regions (Qiangtang Basin and Qaidam Basin), GSMaP-V07 had better performances than other products; and finally, although GSMaP-V07 showed higher overestimation than IMERG-V06B product at hourly scale, it has better consistency with rain-gauge observations. For satellite precipitation data application within the TP, we recommend the GSMaP-V07 over the IMERG-V06B. Furthermore, improvement on the multisatellite rainfall retrieval algorithm is required.

A multi-channel high-throughput chiral molecule determination method based on weak value amplification (WVA) is proposed for the first time. This method can be used for high-throughput and high-precision determination of chiral molecule. Through the design of multi-channel weak measurement system, we realized the real-time, high-throughput, high-sensitivity and high-resolution detection of chiral molecules by selecting proper measurement states. In this work, we have realized a sensitivity of 11.8 nm/° and a resolution of 3.13 × 10-4° for measuring optical rotation. Moreover, the proposed method is successfully applied for detection of lactose content in milk samples. Furthermore, the system has the advantages of simple and robust real-time detection settings, strong stability, high measurement efficiency and good scalability. This method has important significance in clinical diagnosis, food safety and biological system.

Abstract Stretchable hydrogels have been used for a number of biomedical applications. This research focused on the study of a highly stretchable and tough hydrogel made of gelatin and polyacrylamide towards transdermal drug delivery applications. Four drug compounds, nicotine, lidocaine hydrochloride, diltiazem hydrochloride and diclofenac sodium, were used for the evaluation. The release rates of these compounds follow an order: lidocaine > diltiazem > nicotine > diclofenac, which showed a strong correlation between the release rate with their solubility in water at pH 5.5. The kinetics study showed a linear and sustainable release of all tested drugs in the first 8 hours. Experiments were conducted in vitro on replicated human skin. Cytotoxicity studies indicate hydrogel is nontoxic to human cells. The highly stretchable and tough characters of the hydrogel the strength of the hydrogel reduce the severity of wear and tear issues over time for transdermal drug release.

Since acoustic agglomeration is an effective pre-treatment technique for removing fine particles, it can be considered as a potential technology for applications in aerosol pollution control, industrial dust and mist removal, and cloud and precipitation interference. In this study, the cloud-precipitation interference effect was evaluated in situ based on a multi-dimensional multi-scale monitoring system. The variations in the spatial and temporal distribution of rainfall near the surface and the characteristics of precipitation droplets in the air were investigated. The results indicate that strong low-frequency acoustic waves had a significant impact on the macro-characteristics of rainfall clouds, the microphysical structure of rain droplets and near-surface precipitation, and various microwave parameters. In terms of physical structure, the precipitation cloud’s base height decreased significantly upon opening the acoustic device, while agglomeration and de-agglomeration of raindrops were in a dynamic equilibrium. When the sound generator was on, the particle concentration at a sampling attitude of 500−1700 m and the proportion of particles with diameters of 1–1.5 mm decreased significantly (by 1–5 ln [1/m3·mm]). In contrast, the particle concentration increased by 1–3 ln [1/m3·mm] at a sampling attitude below 400 m. Moreover, during acoustic interference, the reflectivity factor surged by 2.71 dBZ within 1200 m of the operation centre. Overall, the spatial and temporal distributions of rainfall rates and cumulative precipitation within 5 km of acoustic operation were uneven and influenced by local terrain and background winds.

Abstract Biological lasers which utilize Fabry–Pérot (FP) cavities have attracted tremendous interest due to their potential in amplifying subtle biological changes. Transverse laser modes generated from cells serve as distinct fingerprints of individual cells; however, most lasing signals lack the ability to provide key information about the cell due to high complexity of transverse modes. The missing key, therefore, hinders it from practical applications in biomedicine. This study reveals the key mechanism governing the frequency distributions of transverse modes in cellular lasers. Spatial information of cells including curvature can be interpreted through spectral information of transverse modes by means of hyperspectral imaging. Theoretical studies are conducted to explore the correlation between the cross‐sectional morphology of a cell and lasing frequencies of transverse modes. Experimentally, the spectral characteristics of transverse modes are investigated in live and fixed cells with different morphological features. By extracting laser modes in frequency domain, the proposed concept is applied for studying cell adhesion process and cell classification from rat cortices. This study expands a new analytical dimension of cell lasers, opening an avenue for subcellular analysis in biophotonic applications.

Vitamin D is a precursor of the steroid hormone 1,25-dihydroxyvitamin D3, and its deficiency is associated with many adverse health outcomes. Here, Revez et al. perform a genome-wide association study for circulating 25-hydroxyvitamin D in 417,580 individuals and test for potential causal relationships with other traits using Mendelian randomization.

The choice of Z-R relationship is an essential source of error in radar Quantitative Precipitation Estimation (QPE). A QPE algorithm combining the Optimization process of precipitation Classification and Dynamical adjustments (OCD) is proposed to improve the accuracy of QPE in Yinchuan city, China. A detailed evaluation and study of Z = 300R1.4 (fixed Z-R), Optimization Processing (OP), Optimization processing of Dynamical Adjustments (ODA) and OCD were performed using various evaluation metrics. The results show that ODA and OCD can significantly reduce the error of QPE, with OCD being the best estimator, reaching a correlation coefficient (CC) of 0.7 and reducing mean absolute error (MAE) and root mean square error (RMSE) by 31% and 34%, respectively. OCD outperforms other algorithms in terms of MAE and RMSE for different rain rates (RR), and the various assessment metrics at hourly scales are also more concentrated in reasonable intervals. OP gives fair results at weaker rain rates (0.2 ≤ RR < 8 mm/h) but underestimates rainfall more incorrectly at stronger rain rates (8 mm/h ≤ RR). Both the OCD and ODA provide a more significant improvement in the estimation of the area and magnitude of strong rainfall, with the OCD providing a better description of the local characteristics of the rainfall distribution, further demonstrating the advantages of the ODA.

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel, predominantly expressed in a subset of peripheral sensory neurons for pain signaling. Topical application of agonist capsaicin for desensitizing TRPV1 currents has been approved for relief of chronic pain. However, the potent TRPV1 capsaicin is not ingestible and even topical capsaicin causes common side effects such as skin irritation, swelling, erythema and pruritus, suggesting that a mild TRPV1 agonist might be helpful for reducing side effects while reliving pain. In this study, we reported on a partial and selective TRPV1 agonist 4-(5-chloropyridin-2-yl)-N-(1H-indazol-6-yl)piperazine-1-carboxamide named CPIPC that was modified based on targeting the residue Arg557, important for conversion between the channel antagonism and agonism. Whole-cell patch clamp recordings indicated a concentration-dependent activation of TRPV1 currents by CPIPC with an EC50 of 1.56 ± 0.13 μM. The maximum efficacy of CPIPC (30 μM) was about 60% of saturated capsaicin (10 μM). Repetitive additions of CPIPC caused TRPV1 current desensitization in both TRPV1-expressing HEK293 cells and dorsal root ganglion (DRG) sensory neurons. Oral administration of CPIPC dose-dependently alleviated inflammatory pain in mice. Further site-directed mutagenesis combined with molecular docking revealed that residue Arg557 is critical for TRPV1 activation by CPIPC. Taken together, we identified a novel partial and selective TRPV1 agonist CPIPC that exhibits antinociceptive activity in mice.

Tea is one of the three most popular nonalcoholic beverages globally and has extremely high economic and cultural value. Currently, the classification, taxonomy, and evolutionary history of the tea family are largely elusive, including phylogeny, divergence, speciation, and diversity. For understanding the evolutionary history and dynamics of species diversity in Theaceae, a robust phylogenetic framework based on 1785 low-copy and 79,103 multi-copy nuclear genes from 91 tea plant genomes and transcriptome datasets had been reconstructed. Our results maximumly supported that the tribes Stewartieae and Gordonieae are successive sister groups to the tribe Theeae from both coalescent and super matrix ML tree analyses. Moreover, in the most evolved tribe, Theeae, the monophyletic genera Pyrenaria, Apterosperma, and Polyspora are the successive sister groups of Camellia. We also yield a well-resolved relationship of Camellia, which contains the vast majority of Theaceae species richness. Molecular dating suggests that Theaceae originated in the late L-Cretaceous, with subsequent early radiation under the Early Eocene Climatic Optimal (EECO) for the three tribes. A diversification rate shift was detected in the common ancestors of Camellia with subsequent acceleration in speciation rate under the climate optimum in the early Miocene. These results provide a phylogenetic framework and new insights into factors that likely have contributed to the survival of Theaceae, especially a successful radiation event of genus Camellia members to subtropic/tropic regions. These novel findings will facilitate the efficient conservation and utilization of germplasm resources for breeding cultivated tea and oil-tea. Collectively, these results provide a foundation for further morphological and functional evolutionary analyses across Theaceae.

Abstract Lasers are the pillars of modern photonics and sensing. Recent advances in microlasers have demonstrated its extraordinary lasing characteristics suitable for biosensing. However, most lasers utilized lasing spectrum as a detection signal, which can hardly detect or characterize nanoscale structural changes in microcavity. Here the concept of amplified structured light‐molecule interactions is introduced to monitor tiny bio‐structural changes in a microcavity. Biomimetic liquid crystal droplets with self‐assembled lipid monolayers are sandwiched in a Fabry–Pérot cavity, where subtle protein‐lipid membrane interactions trigger the topological transformation of output vector beams. By exploiting Amyloid β (Aβ)‐lipid membrane interactions as a proof‐of‐concept, it is demonstrated that vector laser beams can be viewed as a topology of complex laser modes and polarization states. The concept of topological‐encoded laser barcodes is therefore developed to reveal dynamic changes of laser modes and Aβ‐lipid interactions with different Aβ assembly structures. The findings demonstrate that the topology of vector beams represents significant features of intracavity nano‐structural dynamics resulted from structured light‐molecule interactions.

Based on drilling, logging, test production and dynamic monitoring data, the control effects of low-amplitude structure on hydrocarbon accumulation and development performance of ultra-low permeability reservoirs were discussed by using the methods of dense well pattern, multi-factor geological modeling, macro and micro analysis and static and dynamic analysis. The results show that the low-amplitude structure always had a significant control and influence on the distribution and accumulation of original hydrocarbon and water and the evolution trend of water flooding performance in ultra-low permeability reservoirs, and it was not only the direction of oil and gas migration, but also a favorable place for relative accumulation of oil and gas. The controlling effect of low-amplitude structure on ultra-low permeability reservoir mainly depended on its tectonic amplitude and scale; the larger the tectonic amplitude and scale, and the higher the tectonic position of the low amplitude structure, the better the reservoir characteristic parameters, oil and gas enrichment degree and development effect, and the larger the spatial scope it controlled and influenced; water cut and oil well output always fluctuated orderly with the height of the low-amplitude structure; the dynamic response of waterflooding was closely related to the relative structural position of the injection and production wells; the injected water always advanced to the low-lying area of the structure first and then moved up to the high-lying area of the structure gradually; with the continuous expansion of the flooded area, part of the oil and gas in the low-lying part of the structure was forced to be distributed to the high part of the structure, resulting in a new oil and gas enrichment, so that the dynamic reserves of oil wells in the high part increased, and the production capacity remained stable. Key words: ultra-low permeability reservoirs, low-amplitude structure, oil-gas-water enrichment, development dynamics, control effect

Abstract Background The activity of MP1, a pyrrolomycin, was studied in MYCN amplified neuroblastoma (NB) alone and combined with temsirolimus (TEM). Methods Activity of MP1 was tested in MYCN amplified (BE-2c, IMR) and non amplified (SKN-AS) NB cells. The effect of MP1 on MYCN, MCL-1, cleaved PARP, LC3II/LC3I, bcl-2, BAX, and BRD-4 were determined by western blot and RNAseq. The effect of MP1 on metabolism, mitochondrial morphology, and cell cycle was determined. Toxicology and efficacy of MP1 plus TEM were evaluated. Results The IC50 of MP1 was 0.096 μM in BE-2c cells compared to 0.89 μM in IMR, and >50 μM in SKN-AS. The IC50 of MP1 plus TEM in BE-2c cells was 0.023 μM. MP1 inhibited metabolism leading to quiescence and produced a decline in cell cycle S-phase. Electron microscopy showed cristae loss and rounding up of mitochondria. Gene and protein expression for MYCN and MCL-1 declined while LCII and cleaved PARP increased. Protein expression of BAX, bcl-2, and BRD-4 were not significantly changed after MP1 treatment. The in-vivo concentrations of MP1 in blood and tumor were sufficient to produce the biologic effects seen in-vitro. MP1 plus TEM produced a complete response in 3 out of 5 tumor bearing mice. In a second mouse study, the combination of MP1 and TEM slowed tumor growth compared to control. Conclusions MP1 has a potent inhibitory effect on the viability of MYCN amplified NB. Inhibition of metabolism by MP1 induced quiescence and autophagy with a favorable toxicology and drug distribution profile. When combined with TEM anti-tumor activity was potentiated in-vitro and in-vivo.

Quorum sensing in the phycosphere refers to a sensor system in which bacteria secrete bioactive compounds to coordinate group behavior relying on cell density. It is an important way for algae and bacteria to communicate with each other and achieve interactions. It has been determined that quorum sensing is widely presented in the marine phycosphere, which involves a variety of bioactive compounds. Focused on these compounds in marine phycosphere, this review summarizes the types and structures of the compounds, describes the methods in detection and functional evaluation, discusses the ecological functions regulated by the compounds, such as modulating microbial colonization, achieving algae–bacteria mutualism or competition and contributing to marine biogeochemical cycles. Meanwhile, the application prospects of the compounds are also proposed, including controlling harmful algal blooms and producing biofuel. Future research should focus on improving detection techniques, developing more model systems and investigating the effects of climate change on the quorum-sensing pathway to further understand the mechanism and application potential of quorum sensing compounds. This review aims to present an overview of current research carried out in order to provide the reader with perspective on bioactive compounds involved in quorum sensing.

DNA methylation has been reported as one of the most critical epigenetic aberrations during the tumorigenesis and development of breast cancer (BC). This study explored a novel promoter CpG-based signature for long-term survival prediction of BC patients. We used The Cancer Genome Atlas (TCGA) data as training set, and results were validated in an independent dataset from Gene Expression Omnibus (GEO). First, the differential methylation CpG sites were screened in TCGA dataset, of which the candidate promoter CpG sites were preliminarily identified with the univariate Cox regression analysis and the least absolute shrinkage and selection operator regression analysis. Second, the signature was constructed with stepwise regression analysis and multivariate Cox proportional hazards model, which was validated with the survival analysis of two cohorts each from TCGA and GEO databases. The 10-year receiver operating characteristic curves of risk score presented an area under the curve of over 0.7 for both cohorts. A nomogram was also constructed and released. Moreover, Gene Set Enrichment Analysis was performed to identify the more active pathways in high-risk patients. The CpG sites–target gene correlations and differential methylation regions were further explored. In conclusion, the promoter CpG-based signature exhibited good prognostic prediction efficacy in the long-term overall survival of BC patients.

The investigation of atmospheric characteristics is of great significance in properly exploiting air and water resources, and quantitatively estimating and nowcasting precipitation. Microwave radiometers are widely used in this field because they can operate unattended for a long time under almost all weather conditions, and obtain high-quality remote sensing data. This research focuses on the applications of ground-based microwave radiometers in retrieving meteorological characteristics of the Qinghai–Tibet Plateau (QTP) during the East Asian winter monsoon (EAWM), such as humidity and temperature structures, stability/convection indices, and cloud and precipitation retrievals. Vertical structures of atmospheric temperature, pressure, humidity, and other variables were investigated under clear-sky and snowy-sky conditions. The statistical characteristics of stability/convection indices in the QTP region, such as convective available potential energy (CAPE) and convective inhibition (CIN), were investigated, with a special focus on snowy-sky conditions. The relationship between potential cloud water resources and atmospheric and thermodynamics and instability conditions were taken into consideration. The results showed that the peak CAPEs under clear-sky and snowy-sky conditions were 1349.11 J/kg and 1165.12 J/kg, which were relatively larger than the corresponding values during the summer monsoon. CINs during the EAWM were small enough to be negligible. For quantitative precipitation forecasting (QPF), brightness temperatures at 30.0 GHz and 51.24 GHz sampling channels were sensitive to the snowfall process. Within 1 h before snowfall, the precipitable water vapour (PWV) and liquid water content (LWC) increased sharply by 0.05 cm and 0.12 mm, respectively, while the CAPE and downwards CAPE decreased by 225.60 J/kg and 180.31 J/kg, respectively. The findings of this article may be meaningful for characterizing meteorology and precipitation in the QTP and similar regions during the winter monsoon.

Summary: Reliable and sensitive detection of lipase activity is essential for the early diagnosis and monitoring of acute pancreatitis or progression of digestive diseases. However, the available fluorescent probes for detection of lipase activity are only implemented in a hexane-water two-phase system due to the nature of heterogeneous catalysis of lipase, thus limiting their applications in direct imaging of lipase activity in living cells and tissues. Here we designed and synthesized a “turn on” fluorescent probe CPP based on self-assembled micelles for hydrolysis of lipase. The CPP probe exhibits high selectivity and excellent sensitivity for the detection of lipase in such a homogeneous system and is successfully applied for monitoring lipase activity in pancreatic AR42J cells, tissues, and serums. Taken together, the fluorescent CPP probe not only provides a tool for diagnostic potential in pancreatic disease but also demonstrates an application potential for micelle self-assembly-based development of biological probes.

In order to verify the accuracy of precipitable water vapor (PWV) in remote sensing and reanalysis datasets under different climatic conditions and ensure the reliability of analysis results, the performances of ERA-5 reanalysis PWV data and the Atmospheric Infrared Sounder (AIRS) remotely-sensed PWV data were tested in the northern Qinghai-Tibet Plateau by using weather balloon radiosonde data from meteorological stations from 2002 to 2016. The coincidence degree of total cloud cover was also verified, and then the PWV data precision with different levels of cloud cover was analyzed. The results show that: (1) Both ERA-5 and AIRS data underestimate PWV in the studied high plateau region, and higher altitude leads to greater deviation. (2) Compared with AIRS data, ERA-5 data have better consistency with radiosonde data in PWV and total cloud cover. (3) For the long-term trend of PWV, the ERA-5 data are the opposite to the radiosonde data with a clear sky, but both datasets showed a significant increasing trend in cloudy skies. It can be concluded that in high altitude areas, the ERA-5 data can be used for general analysis, but are not well qualified to reflect the changing trend of PWV under climate change.

The characteristics of plateau precipitation and atmosphere, once accurately and comprehensively understood, can be used to inform sound air–water resource development practices. In this study, atmospheric exploration of the Tibet Plateau (TP) was conducted using ground-based microwave radiometer (MWR) data collected during the East Asian summer monsoon. Atmospheric temperature, pressure, humidity, and other variables were gathered under clear-sky, cloudy-sky, and rainy-sky conditions. Statistical characteristics of the air parcel height and stability/convection indices such as convective available potential energy (CAPE) and convective inhibition (CIN) were investigated, with a special focus on the rainy-sky condition. Two retrieval applications for characterizing precipitation, namely short-term precipitation forecast and quantitative precipitation estimation were presented. Results showed that CAPE values in the Darlag region reached extremes around 18:00–20:00 (UTC+8) for cloudy-sky and rainy-sky conditions with corresponding peaks of about 1046.56 J/kg and 703.02 J/kg, respectively. When stratiform or convective–mixed precipitation occurs, the precipitable water vapor (PWV) and CAPE values were generally greater than 1.7 cm and 1000 J/kg, respectively. CAPE values are likely to decrease before the occurrence of precipitation due to the release of the latent heat in the atmosphere.

In this mini-review, we summarize fabrication methods, formation mechanisms, factors that control the characteristics, and applications of self-assembled nanopillars. Nanopillars prepared both in the gas phase and in solutions are discussed.

Both femtosecond and dual-wavelength picosecond operations of Nd,La:SrF2 disordered crystal laser have been demonstrated for the first time. In femtosecond operation, the laser generated mode-locked pulses with pulse duration of 156 fs, which is an average power of 90 mW, and a repetition rate of 108 MHz at the central wavelength of 1057 nm. In dual-wavelength picosecond operation, the laser generated synchronously mode-locked pulses with an average power of 500 mW and pulse duration of 9.9 ps. The mode-locked spectrum clearly shows two peaks at 1050.8 and 1059.0 nm, respectively. A periodic beat frequency of 2.2 THz is observed from the intensity autocorrelation trace, indicating the synchronous dual-wavelength mode-locking. Our experimental results show that Nd,La:SrF2 disordered crystal is an excellent laser material for femtosecond and dual-wavelength lasers near 1 μm wavelength.

In semiarid areas, cereal crops often allocate more biomass to root at the expense of aboveground yield. A pot experiment was conducted to investigate carbon consumption of roots and its impact on grain yield of spring wheat (Triticum aestivum L.) as affected by water and phosphorus (P) supply. A factorial design was used with six treatments namely two water regimes (at 80–75% and 50–45% field capacity (FC)) and three P supply rates (P1=0, P2=44 and P3=109 μg P g−1 soil). At shooting and flowering stages, root respiration and carbon consumption increased with the elevate of P supply rates, regardless of water conditions, which achieved the minimum and maximum at P1 under 50–45% FC and P3 under 80–75% FC, respectively. However, total aboveground biomass and grain yield were higher at P2 under 80–75% FC; and decreased with high P application (P3). The results indicated that rational or low P supply (80–75% of field water capacity and 44 mg P kg−1 soil) should be recommended to improve grain yield by decreasing root carbon consumption in semiarid areas.

The spin-column system for the isolation of nucleic acids (NAs) from multiple samples presents the inconvenience of repeated experimentation, time-consumption, and the risk of contamination in the process of the spin-column exchange. Herein, we propose a convenient and universal assay that can be used to diagnose multiple pathogens using a multi-sample preparation assay. The multi-sample preparation assay combines a 96-well filter/membrane plate, a bio-micromaterial lattice-like micro amine-functional diatomaceous earth (D-APDMS), and homobifunctional imidoesters (HI) for the processing of pathogen enrichment and extraction for multiple samples simultaneously. The purity and quantity of the extracted NAs from pathogens (E. coli and Brucella) using the proposed assay is superior to that of the commercialized spin-column kit. The assay also does not require the replacement of several collection tubes during the reaction processing. For the multi-sample testing, we used as many as six samples simultaneously with the proposed assay. This assay can simultaneously separate up to 96 NAs from one plate, and the use of multichannel pipettes allows faster and simpler experimentation. Therefore, we believe it is a convenient and easy process, and can be easily integrated with other detection methods for clinical diagnostics.

Invasive aspergillosis (IA) is an important cause of morbidity and mortality among immunocompromised people. Imaging and specimen tests used in the clinical diagnosis of aspergillosis with weak and indistinct defects leads to delay in the treatment of early aspergillosis patients. The developing molecular techniques provide a new method for the aspergillosis diagnosis. However, the existing methods are complex, time-consuming and may even be potentially hazardous. In this study, we developed a simple and rapid Aspergillus fumigatus spores DNA isolation assay using synthesized zinc oxide (ZnO). ZnO nanoparticles were used to take the place of the traditional commercial lysis buffer. The quality and quantity of the extracted DNA were sufficient for further diagnostics with polymerase chain reaction (PCR) analysis. This method offers easy, green, and economic alternative DNA isolation for the diagnosis of invasive aspergillosis.

Since the outbreak of the 2019 novel coronavirus disease (COVID-19), the medical research community is vigorously seeking a treatment to control the infection and save the lives of severely infected patients. The main potential candidates for the control of viruses are virally targeted agents. In this short letter, we report our calculations on the inhibitors for the SARS-CoV-2 3CL protease and the spike protein for the potential treatment of COVID-19. The results show that the most potent inhibitors of the SARS-CoV-2 3CL protease include saquinavir, tadalafil, rivaroxaban, sildenafil, dasatinib, etc. Ergotamine, amphotericin b, and vancomycin are most promising to block the interaction of the SARS-CoV-2 S-protein with human ACE-2.

Stretchable and tough hydrogels have drawn a lot of attention recently. Due to their unique properties, they have great potential in the application in areas such as mechanical sensing, wound healing, and drug delivery. In this review, we will summarize recent developments of stretchable and tough hydrogels in these areas.

We report on a passively Q-switched fiber laser with black phosphorus as saturable absorber. By employing the sol-gel fabricated large-mode-area Tm-doped fiber as gain medium, a high-energy Q-switched fiber laser has been demonstrated which delivers the maximum pulse energy of 11.72 μJ with the pulse width of 660 ns at the wavelength of 1954 nm. Our experimental results indicate that BP Q-switched large-mode-area Tm-doped fiber laser is an effective and reliable approach to generate high-energy pulses at 2 μm.

Infectious diseases, especially pathogenic infections, are a growing threat to public health worldwide. Since pathogenic bacteria usually exist in complex matrices at very low concentrations, the development of technology for rapid, convenient, and biocompatible sample enrichment is essential for sensitive diagnostics. In this study, a cucurbit[6]uril (CB) supermolecular decorated amine-functionalized diatom (DA) composite was fabricated to support efficient sample enrichment and in situ nucleic acid preparation from enriched pathogens and cells. CB was introduced to enhance the rate and effectiveness of pathogen absorption using the CB–DA composite. This novel CB–DA composite achieved a capture efficiency of approximately 90% at an Escherichia coli concentration of 106 CFU/mL within 3 min. Real-time PCR analyses of DNA samples recovered using the CB–DA enrichment system showed a four-fold increase in the early amplification signal strength, and this effective method for capturing nucleic acid might be useful for preparing samples for diagnostic systems.

Disassortative mating refers to the phenomenon in which individuals with dissimilar genotypes and/or phenotypes mate with one another more frequently than would be expected by chance. Although the existence of disassortative mating is well established in plant and animal species, the only documented example of negative assortment in humans involves dissimilarity at the major histocompatibility complex (MHC) locus. Previous studies investigating mating patterns at the MHC have been hampered by limited sample size and contradictory findings. Inspired by the sparse and conflicting evidence, we investigated the role that the MHC region played in human mate selection using genome-wide association data from 872 European American spouses from the Health and Retirement Study (HRS). First, we treated the MHC region as a whole, and investigated genomic similarity between spouses using three levels of genomic variation: single-nucleotide polymorphisms (SNPs), classical human leukocyte antigen (HLA) alleles (both four-digit and two-digit classifications), and amino acid polymorphisms. The extent of MHC dissimilarity between spouses was assessed using a permutation approach. Second, we investigated fine scale mating patterns by testing for deviations from random mating at individual SNPs, HLA genes, and amino acids in HLA molecules. Third, we assessed how extreme the spousal relatedness at the MHC region was compared to the rest of the genome, to distinguish the MHC-specific effects from genome-wide effects. We show that neither the MHC region, nor any single SNPs, classic HLA alleles, or amino acid polymorphisms within the MHC region, were significantly dissimilar between spouses relative to non-spouse pairs. However, dissimilarity in the MHC region was extreme relative to the rest of genome for both spousal and non-spouse pairs. Despite the long-standing controversy, our analyses did not support a significant role of MHC dissimilarity in human mate choice.

Medium- and long-term runoff forecasting is essential for hydropower generation and water resources coordinated regulation in the Yellow River headwaters region. Climate change has a great impact on runoff within basins, and incorporating different climate information into runoff forecasting can assist in creating longer lead-times in planning periods. In this paper, a multimodel approach was developed to further improve the accuracy and reliability of runoff forecasting fully considering of large-scale and local-scale climatic factors. First, with four large-scale atmospheric oscillations, sea surface temperature, precipitation, and temperature as the predictors, multiple linear regression (MLR), radial basis function neural network (RBFNN), and support vector regression (SVR) models were built. Next, a Bayesian model averaging (BMA)-based multimodel was developed using weighted MLR, RBFNN, and SVR models, and the performance of the BMA-based multimodel was compared to those of the MLR, RBFNN, and SVR models. Finally, the high-runoff performance of these four models was further analyzed to prove the effectiveness of each model. The BMA-based multimodel performed better than those of the other models, as well as high-runoff forecasting. The results also revealed that the performance of the forecasting models with multiple climatic factors were generally superior to that without climatic factors. The BMA-based multimodel with climatic factors not only provides a promising, reliable method for medium- and long-term runoff forecasting, but also facilitates uncertainty estimation under different confidence intervals.