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BackgroundThe hospital supply chain has revealed increasing vulnerabilities and disruptions in the wake of the COVID-19 pandemic, threatening the healthcare services and patient safety. The resilience of hospital supply chains has emerged as a paramount concern within the healthcare system. However, there is a lack of systematic research to develop an instrument tailored to the healthcare industry that is both valid and reliable for measuring hospital supply chain resilience. Therefore, this study aims to construct and validate a comprehensive scale for assessing hospital supply chain resilience, based on dynamic capability theory.MethodsThis study followed rigorous scale development steps, starting with a literature review and 15 semi-structured interviews to generate initial items. These items were then refined through expert panel feedback and three rounds of Delphi studies. Using data from 387 hospitals in Province S, mainland China, the scale underwent rigorous testing and validation using structural equation modeling. To ensure the most effective model, five alternative models were examined to determine the most suitable parsimonious model.ResultsThe study produced a 26-item scale that captures five dimensions of resilience in line with dynamic capability theory: anticipation, adaptation, response, recovery, and learning, all showing satisfactory consistency, reliability and validity.ConclusionThe multi-dimensional scale offers hospital managers a valuable tool to identify areas needing attention and improvement, benchmark resilience against their counterparts, and ultimately strengthen their supply chains against unexpected risks.

Numerous studies have demonstrated that type 2 diabetes (T2D) is closely linked to the occurrence of Alzheimer’s disease (AD). Nevertheless, the underlying mechanisms for this association are still unknown. Insulin resistance (IR) hallmarked by hyperinsulinemia, as the earliest and longest-lasting pathological change in T2D, might play an important role in AD. Since hyperinsulinemia has an independent contribution to related disease progressions by promoting inflammation in the peripheral system, we hypothesized that hyperinsulinemia might have an effect on microglia which plays a crucial role in neuroinflammation of AD. In the present study, we fed 4-week-old male C57BL/6 mice with a high-fat diet (HFD) for 12 weeks to establish IR model, and the mice treated with standard diet (SD) were used as control. HFD led to obesity in mice with obvious glucose and lipid metabolism disorder, the higher insulin levels in both plasma and cerebrospinal fluid, and aberrant insulin signaling pathway in the whole brain. Meanwhile, IR mice appeared impairments of spatial learning and memory accompanied by neuroinflammation which was characterized by activated microglia and upregulated expression of pro-inflammatory factors in different brain regions. To clarify whether insulin contributes to microglial activation, we treated primary cultured microglia and BV2 cell lines with insulin in vitro to mimic hyperinsulinemia. We found that hyperinsulinemia not only increased microglial proliferation and promoted M1 polarization by enhancing the production of pro-inflammatory factors, but also impaired membrane translocation of glucose transporter 4 (GLUT4) serving as the insulin-responding glucose transporter in the processes of glucose up-taking, reduced ATP production and increased mitochondrial fission. Our study provides new perspectives and evidence for the mechanism underlying the association between T2D and AD.

Genogroup II genotype 4 (GII.4) norovirus causes acute gastroenteritis in children, and its infection is more severe than that of other genotypes. Early and precise detection and treatment are critical for controlling its spread and reducing the severity of infection. In this study, a rapid and efficient isothermal assay for the GII.4 norovirus detection (GII.4-CRISPR detection) was developed based on the CRISPR/Cas13a system. The assay can be applied without expensive instrumentation, and the results can be read via both fluorescence and lateral flow strip (LFS). The analytical sensitivity of this assay was 5 copies/reaction, and there was no cross-reaction with other genotypes of norovirus or other clinically common pathogens. There was a coincidence rate of 100% between our assay and commercial quantitative polymerase chain reaction. GII.4-CRISPR detection improves upon the shortcomings of some previously established molecular methods of detection, particularly with regard to accessibility. It provides an alternative tool for outbreak control and early diagnosis of GII.4 norovirus infection.

The white spot syndrome virus is the most destructive virus threatening the shrimp industry worldwide, causing hundreds of millions of dollars in economic losses each year. There is currently no specific medicine to treat it. Therefore, rapid and accurate detection of WSSV is of great significance for controlling its spread and reducing economic losses. Traditional detection methods, such as polymerase chain reaction (PCR) and quantitative fluorescent PCR, rely on laboratory equipment and are not suitable for field testing. In this study, recombinase polymerase amplification (RPA) combined with a lateral flow strip (LFS) was developed. This method targets the entire genome and designs primers and probes accordingly. The detection can be completed in 30 min at 37°C, and the detection limit of each reaction is 20 copies, which is much more sensitive than other detection methods. The RPA-LFS method is highly specific to the white spot syndrome virus and has no cross-reactivity with other common shrimp viruses or pathogens. In total, 100 field samples were tested and compared to the real-time PCR method. Both methods detected 8 positive results, and the positive detection rate was 100%. The method was fast, simple, specific, and sensitive. It does not rely on laboratory equipment and has broad application prospects for in-field detection, especially in remote areas with underdeveloped medical equipment.

Atherosclerosis is the major pathophysiological basis of cerebrovascular and cardiovascular diseases. Vascular smooth muscle cells (VSMCs) constitute the main structure of vasculature and play important roles in maintaining vascular tone and blood pressure. Many biological processes and cellular signaling events involved in atherosclerogenesis have been shown to converge on deregulating VSMC functions. However, the molecular mechanisms underlying dysfunctional VSMC in atherosclerosis are still poorly defined. Recent evidence revealed that circular RNAs (circRNAs) are closely related to diseases such as degenerative diseases, tumor, congenital diseases, endocrine diseases and cardiovascular diseases. Several studies demonstrated that circRNAs (e.g., circACTA2, Circ-SATB2, circDiaph3, circ_0020397, circTET3, circCCDC66) played critical roles in the regulation of VSMC proliferation, migration, invasion, and contractile-to-synthetic phenotype transformation by sponging microRNAs (e.g., miR-548f-5p, miR-939, miR-148a-5p, miR-138, miR-351-5p, miR-342-3p). This review describes recent progress in the profiling of circRNAs by transcriptome analysis in VSMCs and their molecular functions in regulating VSMC proliferation and migration.

Unlike past health crises that were more localized, the highly contagious coronavirus disease 2019 (COVID-19) crisis is impacting the world to an unprecedented extent. This is the first study examining how and whether the COVID-19 pandemic affects herding behavior in the Eastern European stock markets. Using samples from the stock markets of Russia, Poland, the Czech Republic, Hungary, Croatia, and Slovenia from January 1, 2010 to March 10, 2021, we demonstrate that the COVID-19 pandemic has increased herding behavior in all the sample stock markets. Our results show that the COVID-19 crisis reinforces the impact of global market returns on herding behavior in these specific stock markets. We find that COVID-19 strengthens the spillover effect of regional herding on herding behavior. Thus, financial authorities should monitor investors in the stock market to avoid the increase in herding behavior as well as the reinforcement of the global market returns and regional return dispersion on herding during the period of pandemic.

A continuous increase in ambient temperature caused by global warming has been considered a worldwide threat. As sessile organisms, plants have evolved sophisticated heat shock response (HSR) to respond to elevated temperatures and other abiotic stresses, thereby minimizing damage and ensuring the protection of cellular homeostasis. In particular, for perennial trees, HSR is crucial for their long life cycle and development. HSR is a cell stress response that increases the number of chaperones including heat shock proteins (HSPs) to counter the negative effects on proteins caused by heat and other stresses. There are a large number of HSPs in plants, and their expression is directly regulated by a series of heat shock transcription factors (HSFs). Therefore, understanding the detailed molecular mechanisms of woody plants in response to extreme temperature is critical for exploring how woody species will be affected by climate changes. In this review article, we summarize the latest findings of the role of HSFs and HSPs in the HSR of woody species and discuss their regulatory networks and cross talk in HSR. In addition, strategies and programs for future research studies on the functions of HSFs and HSPs in the HSR of woody species are also proposed.

Hand, foot, and mouth disease (HFMD) is a common infectious disease affecting mainly children under 5 years of age. Coxsackievirus A6 (CVA-6), a major causative pathogen of HFMD, has caused outbreaks in recent years. Currently, no effective vaccine or antiviral treatments are available. In this study, one-step reverse-transcription recombinase polymerase amplification (RT-RPA), combined with a disposable lateral flow strip (LFS) assay, was developed to detect CVA-6. This assay can be performed in less than 35 min at 37°C without expensive instruments, and the result can be observed directly with the naked eye. The sensitivity of the RT-RPA-LFS was 10 copies per reaction, which was comparable to that of the conventional real-time quantitative polymerase chain reaction (qPCR) assays. Moreover, the assay specificity was 100%. The clinical performance of the RT-RPA-LFS assay was evaluated using 142 clinical samples, and the coincidence rate between RT-RPA-LFS and qPCR was 100%. Therefore, our RT-RPA-LFS assay provides a simple and rapid approach for point-of-care CVA-6 diagnosis.

As an important foodborne pathogen, Vibrio vulnificus gives a significant threat to food safety and public health. Rapid and accurate detection methods for V. vulnificus are required to control its spread. The conventional detection methods are time-consuming and labor-intensive, while the polymerase chain reaction (PCR)- and quantitative PCR (qPCR)-based methods are limited because of their dependence on laboratory equipment. Nucleic acid isothermal amplification technologies have been applied to develop simpler assays. In this study, a rapid detection method based on real-time recombinase polymerase amplification (RPA) targeting the extracellular metalloprotease (empV) gene of V. vulnificus has been established. The method finished the detection in 2–14 min at 39°C with good specificity. The limit of detection was 17 gene copies or 1 colony-forming unit (CFU) per reaction, or 1 CFU/10 g of spiked food with enrichment. In a clinical sample detection test, the results of real-time RPA were 100% consistent with bioassay and qPCR. Moreover, the method could resist the effect of food matrix and could tolerate crude templates. The real-time RPA method established in this study is rapid and simple and has the potential to be widely applied for V. vulnificus detection in food safety control.

On-site detection demands are quickly increasing to control foodborne pathogenic bacteria along with the long food supply chains. Combining the isothermal recombinase polymerase amplification (RPA) with lateral flow strips (LFSs) is a promising molecular detection approach for the short reaction time, low isothermal condition, and simple and “instrument-free” procedure. However, the method comes with a non-negligible intrinsic risk of the primer-dependent artifacts. In this study, with an important foodborne pathogenic bacterium Salmonella enterica serotype Typhimurium (S. Typhimurium) as the model, system measures including the careful selection of primers targeting unique virulence genes, use of a probe in the RPA reaction, introducing base substitutions with specific guidelines in the primer and probe sequences, and analyzing and screening the primer–probe complex formation were taken to eliminate the primer-dependent artifacts. The measures were strictly tested for the efficacy, and the standardized method was able to specifically detect S. typhimurium within 30 min at 42°C without any interference of probe–primer signals. The established RPA-LFS method shared high sensitivity with the detection limit of 1 CFU/μl of unpurified culture. Our study provided practical measures for the prevention of false positive signals from primer–dimers or primer–probe complexes when using the RPA–LFS method in pathogen detections, and also established a readily applicable method for S. Typhimurium detection.

Cryptotanshinone (CTs), an active component isolated from the root of Salvia miltiorrhiza (SM), has been shown to exert potent neuroprotective property. We here established an oxygen-glucose deprivation/recovery (OGD/R)-injured Neurovascular Unit (NVU) model in vitro to observe the neuroprotective effects of CTs on cerebral ischemia/reperfusion injury (CIRI), and explore the underlying mechanisms. CTs was observed to significantly inhibit the OGD/R-induced neuronal apoptosis, and decease the activation of Caspase-3 and the degradation of poly-ADP-ribose polymerase (PARP), as well as the increase of Bax/Bcl-2 ratio in neurons under OGD/R condition. The inhibitory effects of CTs on neuron apoptosis were associated with the blocking of mitogen-activated protein kinase (MAPK) signaling pathway. CTs also remarkably ameliorated OGD/R-induced reduction of transepithelial electrical resistance (TEER) values and the increase of transendothelial permeability coefficient (Pe) of sodium fluorescein (SF) by upregulating the expression of ZO-1, Claudin-5, and Occludin in brain microvascular endothelial cells (BMECs), which might be related to the down-regulation of matrix metalloproteinase (MMP)-9 expression. Based on these findings, CTs may play a neuroprotective role in OGD/R injure in NVU models in vitro by inhibiting cell apoptosis and alleviating the damage of blood-brain barrier (BBB).

CO2 uptake and water loss in plants are regulated by microscopic pores on the surface of leaves, called stomata. This enablement of gas exchange by the opening and closing of stomata is one of the most essential processes in plant photosynthesis and transpiration, affecting water-use efficiency (WUE) and thus drought susceptibility. In plant species with crassulacean acid metabolism (CAM) photosynthesis, diel stomatal movement pattern is inverted relative to C3 and C4 photosynthesis species, resulting in much higher WUE and drought tolerance. However, little is known about the molecular basis of stomatal movement in CAM species. The goal of this study is to identify candidate genes that could play a role in stomatal movement in an obligate CAM species, Kalanchoë fedtschenkoi. By way of a text-mining approach, proteins were identified in various plant species, spanning C3, C4, and CAM photosynthetic types, which are orthologous to proteins known to be involved in stomatal movement. A comparative analysis of diel time-course gene expression data was performed between K. fedtschenkoi and two C3 species (i.e., Arabidopsis thaliana and Solanum lycopersicum) to identify differential gene expression between the dusk and dawn phases of the 24-h cycle. A rescheduled catalase gene known to be involved in stomatal movement was identified, suggesting a role for H2O2 in CAM-like stomatal movement. Overall, these results provide new insights into the molecular regulation of stomatal movement in CAM plants, facilitating genetic improvement of drought resistance in agricultural crops through manipulation of stomata-related genes.

Ecto- and endo-mycorrhizal colonization of Populus roots have a positive impact on the overall tree health and growth. A complete molecular understanding of these interactions will have important implications for increasing agricultural or forestry sustainability using plant:microbe-based strategies. These beneficial associations entail extensive morphological changes orchestrated by the genetic reprogramming in both organisms. In this study, we performed a comparative analysis of two Populus species (Populus deltoides and P. trichocarpa) that were colonized by either an arbuscular mycorrhizal fungus (AmF), Rhizophagus irregularis or an ectomycorrhizal fungus (EmF), Laccaria bicolor, to describe the small RNA (sRNA) landscape including small open reading frames (sORFs) and micro RNAs (miRNAs) involved in these mutualistic interactions. We identified differential expression of sRNAs that were, to a large extent, (1) within the genomic regions lacking annotated genes in the Populus genome and (2) distinct for each fungal interaction. These sRNAs may be a source of novel sORFs within a genome, and in this regard, we identified potential sORFs encoded by the sRNAs. We predicted a higher number of differentially-expressed miRNAs in P. trichocarpa (4 times more) than in P. deltoides (conserved and novel). In addition, 44 miRNAs were common in P. trichocarpa between the EmF and AmF treatments, and only 4 miRNAs were common in P. deltoides between the treatments. Root colonization by either fungus was more effective in P. trichocarpa than in P. deltoides, thus the relatively few differentially-expressed miRNAs predicted in P. deltoides might reflect the extent of the symbiosis. Finally, we predicted several genes targets for the plant miRNAs identified here, including potential fungal gene targets. Our findings shed light on additional molecular tiers with a role in Populus-fungal mutualistic associations and provides a set of potential molecular targets for future enhancement.

A greater understanding of biosynthesis, signaling and regulatory pathways involved in determining stem growth and secondary cell wall chemistry is important for enabling pathway engineering and genetic optimization of biomass properties. The present study describes a new functional role of PdIQD10, a Populus gene belonging to the IQ67-Domain1 family of IQD genes, in impacting biomass formation and chemistry. Expression studies showed that PdIQD10 has enhanced expression in developing xylem and tension-stressed tissues in Populus deltoides. Molecular dynamics simulation and yeast two-hybrid interaction experiments suggest interactions with two calmodulin proteins, CaM247 and CaM014, supporting the sequence-predicted functional role of the PdIQD10 as a calmodulin-binding protein. PdIQD10 was found to interact with specific Populus isoforms of the Kinesin Light Chain protein family, shown previously to function as microtubule-guided, cargo binding and delivery proteins in Arabidopsis. Subcellular localization studies showed that PdIQD10 localizes in the nucleus and plasma membrane regions. Promoter-binding assays suggest that a known master transcriptional regulator of secondary cell wall biosynthesis (PdWND1B) may be upstream of an HD-ZIP III gene that is in turn upstream of PdIQD10 gene in the transcriptional network. RNAi-mediated downregulation of PdIQD10 expression resulted in plants with altered biomass properties including higher cellulose, wall glucose content and greater biomass quantity. These results present evidence in support of a new functional role for an IQD gene family member, PdIQD10, in secondary cell wall biosynthesis and biomass formation in Populus.

Crassulacean acid metabolism (CAM) improves photosynthetic efficiency under limited water availability relative to C3 photosynthesis. It is widely accepted that CAM plants have evolved from C3 plants and it is hypothesized that CAM is under the control of the internal circadian clock. However, the role that the circadian clock plays in the evolution of CAM is not well understood. To identify the molecular basis of circadian control over CAM evolution, rhythmic gene sets were identified in a CAM model plant species (Kalanchoë fedtschenkoi) and a C3 model plant species (Arabidopsis thaliana) through analysis of diel time-course gene expression data using multiple periodicity detection algorithms. Based on protein sequences, ortholog groups were constructed containing genes from each of these two species. The ortholog groups were categorized into five gene sets based on conservation and diversification of rhythmic gene expression. Interestingly, minimal functional overlap was observed when comparing the rhythmic gene sets of each species. Specifcally, metabolic processes were enriched in the gene set under circadian control in K. fedtschenkoi and numerous genes were found to have retained or gained rhythmic expression in K. fedtsechenkoi. Additonally, several rhythmic orthologs, including CAM-related orthologs, displayed phase shifts between species. Results of this analysis point to several mechanisms by which the circadian clock plays a role in the evolution of CAM. These genes provide a set of testable hypotheses for future experiments.

Although the precise mechanism underlying initial lesion development in multiple sclerosis (MS) remains unclear, CNS inflammation has long been associated with demyelination, and axonal degeneration. The activation of microglia/macrophages, which serve as innate immune cells in the CNS, is the first reaction to even minor pathologic changes in the CNS and is considered an initial pathogenic event in MS. Microglial activation accompanies a variety of gene expressions, including cystatin F (Cys F), which belongs to the cystatin superfamily and is one of the cathepsin inhibitors. In our previous study we showed that Cys F has a unique expression pattern in microglia/macrophages in the demyelination process. Specifically, the timing of Cys F induction correlated with ongoing demyelination, and the sites of Cys F expression overlapped with areas of remyelination. Cys F induction ceased in chronic demyelination when remyelination capacity was lost, suggesting that Cys F expressed by microglia/macrophages may play an important role in demyelination and/or remyelination. The functional role of Cys F in demyelinating disease of the CNS, however, is unclear. Cys F gene knockout mice were used in the current study to clarify the functional role of Cys F in the demyelination process in a cuprizone-induced demyelination animal model. We demonstrated that absence of the Cys F gene and the resulting disinhibition of cathepsin C (Cat C) aggravates the demyelination, and this finding may be related to the increased expression of the glia-derived chemokine, CXCL2, which may attract inflammatory cells to sites of myelin sheath damage. This effect was reversed by knock down of the Cat C gene. The findings gain further insight to function of Cat C in pathophysiology of MS, which may have implications for therapeutics for the prevention of neuroinflammation-involved neurological disorders in the future.