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Abstract Background The diagnosis of tuberculous pleurisy (TP) presents a significant challenge due to the low bacterial load in pleural effusion (PE) samples. Cell-free Mycobacterium tuberculosis DNA (cf-TB) in PE samples is considered an optimal biomarker for diagnosing TP. This study aimed to evaluate the applicability of cf-TB testing across diverse research sites with a relatively large sample size. Methods Patients suspected of TP and presenting with clinical symptoms and radiological evidence of PE were consecutively enrolled by treating physicians from 11 research sites across 6 provinces in China between April 2020 and August 2022. Following centrifugation, sediments obtained from PE were used for Xpert MTB/RIF (Xpert) and mycobacterial culture, while the supernatants were subjected to cf-TB testing. This study employed a composite reference standard to definite TP, which was characterized by any positive result for Mycobacterium tuberculosis (MTB) through either PE culture, PE Xpert, or pleural biopsy. Results A total of 1412 participants underwent screening, and 1344 (95.2%) were subsequently enrolled in this study. Data from 1241 (92.3%) participants were included, comprising 284 with definite TP, 677 with clinically diagnosed TP, and 280 without TP. The sensitivity of cf-TB testing in definite TP was 73.6% (95% CI 68.2–78.4), significantly higher than both Xpert (40.8%, 95% CI 35.3–46.7, P

The soybean mosaic disease—caused by the soybean mosaic virus (SMV)—significantly impacts soybean quality and yield. Among its various strains, SMV-SC7 is prevalent in China. Therefore, rapid and accurate diagnosis is deemed critical to mitigate the spread of SMV-SC7. In this study, a simple and rapid magnetic bead-based RNA extraction method was optimized. Furthermore, a reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay that requires no specialized equipment such as PCR Amplifier was proposed, employing a lateral flow device (LFD) for visual interpretation of SMV-SC7. The RT-LAMP-LFD approach facilitated specificity testing of SMV-SC7. Moreover, the limit of detection (LOD) of this method was as low as 10−5 ng (2.4 copies). The sensitivity of RT-LAMP-LFD was 10-fold higher than that of the colorimetric RT-LAMP method. In 194 field samples tested, the RT-LAMP-LFD detection of the SMV-SC7 had accuracy of 98.45% in comparison to RT-qPCR. In conclusion, the assay exhibited high specificity, sensitivity, and rapidity, enabling economical and portable detection of SMV-SC7 and providing technical support to identify SMV-SC7-infected soybeans.

ABSTRACT Background Abnormal glycosylation is associated with tumors. The clinical value of serum glycans in assessing progression of hepatocellular carcinoma (HCC) patients remains a challenge. Methods A study dynamically comparing levels of fifteen lectin‐specific glycans between preoperative and postoperative serum of 65 HCC patients was conducted via lectin biochip technology. Multivariable logistic regression analysis was used to address associations between serum glycan levels and clinicopathological characteristics. Kaplan–Meier analysis was used to evaluate the impacts of serum glycan levels on overall survival (OS) and progression‐free survival (PFS) of the HCC patients. Results HCC patients presented significantly higher levels of the lectin‐specific glycans in preoperative serum than disease‐free individuals (p

Abstract Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6–18.0) for the immunotherapy group compared with 9.9 months (8.0–11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40–0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3–32.8) for the control group (HR, 0.57 [95% CI, 0.33–0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

Objective To investigate the ocular clinical features and diagnostic and therapeutic protocol of patients with endogenous endophthalmitis (EE) secondary to Klebsiella pneumoniae liver abscess (KPLA). Methods Six patients (seven eyes) with EE secondary to KPLA who attended our hospital from January 2019 to December 2020 were enrolled and analyzed in terms of clinical manifestation, examination findings, treatment regimen, and prognosis. Results All six patients were male, among whom five had pyrexia. All patients had impaired vision, and at initial diagnosis, there were four patients (five eyes) with no light perception, one patient (one eye) with manual vision, and one case (one eye) with light perception. All patients had the typical clinical manifestations of endophthalmitis such as impaired vision, conjunctival congestion and edema, ocular swelling and pain, and inflammatory response in the anterior chamber, and postoperative microbial culture of intraocular fluid showed positive Klebsiella pneumoniae. At the last visit, four patients (four eyes) had loss of vision, one patient (one eye) did not cooperate in vision check, and one patient (two eyes) was lost to follow-up. Conclusion EE secondary to KPLA is highly destructive to eyeball structure and visual function, and patients with KPLA who develop systemic symptoms (such as fever) or ocular discomfort (such as loss of vision, eye redness, and eye pain) should attend the outpatient service of ophthalmology department and receive regular follow-up examination to be alert to the development of endophthalmitis.

In the study, the authors introduce Qi’s normalized remainder of the Maclaurin power series expansion of the function lnsecx=−lncosx; in view of a monotonicity rule for the ratio of two Maclaurin power series and by virtue of the logarithmic convexity of the function (2x−1)ζ(x) on (1,∞), they prove the logarithmic convexity of Qi’s normalized remainder; with the aid of a monotonicity rule for the ratio of two Maclaurin power series, the authors present the monotonic property of the ratio between two Qi’s normalized remainders.

In this paper, by using q-integers and higher-order generalized Fibonacci numbers, we define the higher-order generalized Fibonacci quaternions with q-integer components. We give some special cases of these newly established quaternions. This article examines q-calculus and quaternions together. We obtain a Binet-like formula, some new identities, a generating function, a recurrence relation, an exponential generating function, and sum properties of quaternions with quantum integer coefficients. In addition, we obtain some new identities for these types of quaternions by using three new special matrices.

In this paper, we investigate a class of non-instantaneous impulsive fractional integral equations. Utilizing the Banach contraction mapping principle, we establish the existence and uniqueness of solutions for the considered problem. Additionally, employing Schauder’s fixed-point theorem, we demonstrate the existence of solutions within the framework of β-Banach spaces. Moreover, we examine the β–Ulam–Hyers stability of the solutions, providing insights into the stability behavior under small perturbations. An illustrative example is presented to demonstrate the practical applicability and effectiveness of the theoretical results obtained.

The CO2-based diblock copolymer, poly(ethylene oxide-b-cyclohexene carbonate) (PEO-b-PCHC), was synthesized via ring opening copolymerization (ROCOP) by using PEO as a macro-chain-transfer agent. Theses diblock copolymers were comprehensive characterized by Fourier-transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) to gain insights into their chemical structures and thermal properties. The microphase separation was induced after blending with phenolic resin through medicated by competitive hydrogen bonding interaction between phenolic hydroxyl (OH) group with ether unit of PEO and CO unit of PCHC based on FTIR analyses. Small angle X-ray scattering (SAXS) analyses also provided the self-assembled structures of specific phenolic/PEO-b-PCHC blends following thermal polymerization at 180 °C because of the reaction-induced microphase separation mechanism. Upon removal of PEO-b-PCHC diblock copolymer templates at 350 °C, mesoporous phenolic resins including cylindrical, spherical and worm-like structures were obtained based on SAXS, transmission electron microscope (TEM) and nitrogen adsorption/desorption analyses. Furthermore, the mesoporous carbons were further obtained from mesoporous phenolic resin thermal calcined at 700 °C under N2 atmosphere. These carbonized mesoporous materials exhibited impressive characteristics such as high surface areas and they demonstrated effective CO2 capture capabilities (4.5 mmol g−1 at 273 K). The captured CO2 could subsequently be employed in ROCOP again for synthesizing CO2-based copolymers, aligning with the principles of a circular economy.

Nonlinear analysis has widespread and significant applications in many areas at the core of many branches of pure and applied mathematics and modern science, including nonlinear ordinary and partial differential equations, critical point theory, functional analysis, fixed point theory, nonlinear optimization, fractional calculus, variational analysis, convex analysis, dynamical system theory, mathematical economics, data mining, signal processing, control theory, and many more [...]

Combination therapy consisting of anticancer drugs has been used to decrease the adverse effects and increase the effectiveness of the drugs. The present study aimed to examine the synergistic effect and potential mechanisms of oxaliplatin and nattokinase (NK) combined treatment for BGC-823, HepG-2, HeLa, and NCI-H460 cells. NK was isolated and purified from black soybean natto by dialysis and gel filtration chromatography, which had a nattokinase activity of 600,391 U/g. MTT experiment, clone formation assay, Hoechst 33,342 staining, DCFH-DA staining, and JC-1 staining showed that NK had no cytotoxicity and oxaliplatin could inhibit cell proliferation. Oxaliplatin combined with NK could enhance its anticancer effect and lead to mitochondrial dysfunction by causing the increase of intracellular ROS, which eventually induced apoptosis. Compared to oxaliplatin alone, nattokinase in combination with oxaliplatin can effectively inhibit DNA synthesis and increase cell uptake, ultimately inhibiting cell proliferation. Transwell and angiogenesis experiments proved that the combination of NK and oxaliplatin could more effectively inhibit cell migration, invasion, and in vitro angiogenesis, thereby preventing the spread and metastasis of tumors. RT-qPCR showed that the mechanism of inhibition of cell proliferation and thus induction of apoptosis by the combination of NK and oxaliplatin may be achieved through the upregulation of BAD, BAX, and Caspase-3 genes. Molecular docking results show that NK could act as the carrier of oxaliplatin. In conclusion, the above results suggested that NK could play a synergistic anticancer role with oxaliplatin by inducing apoptosis through the mitochondrial pathway, enhance the sensitivity of cancer cells to oxaliplatin, and provide a new strategy for cancer treatment.

Studies have shown that phosphatase and tensin homolog deleted on chromosome ten (PTEN) participates in the regulation of cochlear hair cell survival. Bisperoxovanadium protects against neurodegeneration by inhibiting PTEN expression. However, whether bisperoxovanadium can protect against noise-induced hearing loss and the underlying mechanism remains unclear. In this study, we established a mouse model of noise-induced hearing loss by exposure to 105 dB sound for 2 hours. We found that PTEN expression was increased in the organ of Corti, including outer hair cells, inner hair cells, and lateral wall tissues. Intraperitoneal administration of bisperoxovanadium decreased the auditory threshold and the loss of cochlear hair cells and inner hair cell ribbons. In addition, noise exposure decreased p-PI3K and p-Akt levels. Bisperoxovanadium preconditioning or PTEN knockdown upregulated the activity of PI3K-Akt. Bisperoxovanadium also prevented H2O2-induced hair cell death by reducing mitochondrial reactive oxygen species generation in cochlear explants. These findings suggest that bisperoxovanadium reduces noise-induced hearing injury and reduces cochlear hair cell loss.

For all-weather, all-day and multi-task warfare requirements, multi-mode composite guidance technology has gradually become a research hotspot in the field of precision guidance in recent years. Compared with common single-mode guidance technology, multi-mode composite guidance technology has played their own advantages and maken up for their disadvantages. In addition, multi-mode composite guidance technology has improved the adaptability of missiles to small and weak targets, stealth targets and complex backgrounds, and has become an important development direction in the field of precision guidance. Based on a brief introduction of the basic concepts of single-mode and multi-mode composite guidance technology, this paper describes the characteristics and principles of multi-mode composite guidance, lists several well-known multi-mode composite guidance weapons abroad, analyzes the development status and trend of multi-mode composite guidance technology, and summarizes the problems faced by multi-mode composite guidance technology.

This paper presents a comprehensive survey of the generalization of hybrid numbers and hybrid polynomials, particularly in the fields of mathematics and physics. In this paper, by using higher-order generalized Fibonacci polynomials, we introduce higher-order generalized Fibonacci hybrid polynomials called higher-order generalized Fibonacci hybrinomials. We obtain some special cases and algebraic properties of the higher-order generalized Fibonacci hybrinomials, such as the recurrence relation, generating function, exponential generating function, Binet formula, Vajda’s identity, Catalan’s identity, Cassini’s identity and d’Ocagne’s identity. We also present three different matrices whose components are higher-order generalized Fibonacci hybrinomials, higher-order generalized Fibonacci polynomials and Lucas polynomials. By using these matrices, we obtain some identities related to these newly established hybrinomials.

In the paper, the authors introduce two notions, the normalized remainders, or say, the normalized tails, of the Maclaurin power series expansions of the sine and cosine functions, derive two integral representations of the normalized tails, prove the nonnegativity, positivity, decreasing property, and concavity of the normalized tails, compute several special values of the Young function, the Lommel function, and a generalized hypergeometric function, recover two inequalities for the tails of the Maclaurin power series expansions of the sine and cosine functions, propose three open problems about the nonnegativity, positivity, decreasing property, and concavity of a newly introduced function which is a generalization of the normalized tails of the Maclaurin power series expansions of the sine and cosine functions. These results are related to the Riemann–Liouville fractional integrals.

In this paper, we introduce and study new features for 2-variable (p,q)-Hermite polynomials, such as the (p,q)-diffusion equation, (p,q)-differential formula and integral representations. In addition, we establish some summation models and their (p,q)-derivatives. Certain parting remarks and nontrivial examples are also provided.

This paper investigates diverse classes of multidimensional Weyl and Doss ρ-almost periodic functions in a general measure setting. This study establishes the fundamental structural properties of these generalized ρ-almost periodic functions, extending previous classes such as m-almost periodic and (equi-)Weyl-p-almost periodic functions. Notably, a new class of (equi-)Weyl-p-almost periodic functions is introduced, where the exponent p>0 is general. This paper delves into the abstract Volterra integro-differential inclusions, showcasing the practical implications of the derived results. This work builds upon the extensions made in the realm of Levitan N-almost periodic functions, contributing to the broader understanding of mathematical functions in diverse measure spaces.

The main aim of this paper is to study new features and specific properties of the Toeplitz operator with radial symbols in harmonic Fock spaces. A new spectral decomposition of a Toeplitz operator with Wick symbols is also established.

Abstract Purpose This study aimed to investigate the impact of CC chemokine receptor 7 (CCR7) on the recruitment and polarization of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC). Methods We analyzed CCR7 expression pattern, clinicopathological significance, and its association with M2 macrophage infiltration in OSCC by bioinformatic methods. Small interfering RNA (siRNA) was utilized to silence CCR7 in OSCC cells. Conditioned media (CM) was harvested from transfected OSCC cells to establish a co-culture model of THP-1 derived macrophages and OSCC cells. Transwell assay and cell adhesion assay were performed to examine the effect of CCR7 on macrophages recruitment and adhesion. Cytoskeleton was labelled by phalloidin to observe macrophage morphological changes. Moreover, phenotypic alteration of macrophages was measured using quantitative real-time PCR (qRT-PCR), flow cytometry, and immunofluorescence (IF) staining. Ultimately, recombinant human CCL19 and CCL21 were added into the medium of THP-1 derived macrophages to explore their effects on polarization in vitro. Results In OSCC patients, the overexpression of CCR7 positively correlated with lymph node metastasis and M2 macrophage infiltration. Macrophage not only exhibited enhanced migration, invasion and adhesion abilities, but also appeared more spindle and branched in vitro when treated with CM from OSCC cells. However, these phenomena were abrogated with knockdown of CCR7. We also discovered that inhibition of CCR7 in OSCC cells suppressed TAMs polarization to an M2 phenotype. In addition, recombinant human CCL19 and CCL21 promoted macrophage M2-polarization in vitro. Conclusion CCR7 in OSCC cells promoted recruitment and M2-polarization of THP-1 derived macrophages in vitro by regulating production of CCL19 and CCL21.

Animal adaptation to environmental challenges is a complex process involving intricate interactions between the host genotype and gut microbiome composition. The gut microbiome, highly responsive to external environmental factors, plays a crucial role in host adaptability and may facilitate local adaptation within species. Concurrently, the genetic background of host populations influences gut microbiome composition, highlighting the bidirectional relationship between host and microbiome. Despite this, our understanding of gut microbiome plasticity and its role in host adaptability remains limited, particularly in reptiles. To clarify this issue, we conducted a reciprocal translocation experiment with gravid females of the Qinghai toad-headed lizards (Phrynocephalus vlangalii) between high-altitude (2 600 m a.s.l.) and superhigh-altitude (3 600 m a.s.l.) environments on Dangjin Mountain of the Qinghai-Xizang Plateau, China. One year later, we assessed the phenotypes and gut microbiomes of their offspring. Results revealed significant plasticity in gut microbiome diversity and structure in response to contrasting elevations. Highaltitude conditions increased diversity, and maternal effects appeared to enable high-altitude lizards to maintain elevated diversity when exposed to superhigh-altitude environments. Additionally, superhigh-altitude lizards displayed distinct gut microbiome structures with notable host specificity, potentially linked to their lower growth rates. Overall, these findings underscore the importance of the gut microbiome in facilitating reptilian adaptation to rapid environmental changes across altitudinal gradients. Furthermore, this study provides critical insights into microbial mechanisms underpinning local adaptation and adaptative plasticity, offering a foundation for future research on host-microbiome interactions in evolutionary and ecological contexts. [ABSTRACT FROM AUTHOR]

Fractional calculus has played a significant role in modeling complex systems in disciplines such as mathematics, physics, biology, and engineering [...]

Large-scale patterns of biodiversity and the underlying mechanisms that regulate these patterns are central topics in biogeography and macroecology. The Qinghai-Tibet Plateau serves as a natural laboratory for studying these issues. However, most previous studies have focused on the entire Qinghai-Tibet Plateau, leaving independent physical geographic subunits in the region less well understood. We studied the current plant diversity of the Kunlun Mountains, an independent physical geographic subunit located in northwestern China on the northern edge of the Qinghai-Tibet Plateau. We integrated measures of species distribution, geological history, and phylogeography, and analyzed the taxonomic richness, phylogenetic diversity, and community phylogenetic structure of the current plant diversity in the area. The distribution patterns of 1911 seed plants showed that species were distributed mainly in the eastern regions of the Kunlun Mountains. The taxonomic richness, phylogenetic diversity, and genera richness showed that the eastern regions of the Kunlun Mountains should be the priority area of biodiversity conservation, particularly the southeastern regions. The proportion of Chinese endemic species inhabiting the Kunlun Mountains and their floristic similarity may indicate that the current patterns of species diversity were favored via species colonization. The Hengduan Mountains, a biodiversity hotspot, is likely the largest source of species colonization of the Kunlun Mountains after the Quaternary. The net relatedness index indicated that 20 of the 28 communities examined were phylogenetically dispersed, while the remaining communities were phylogenetically clustered. The nearest taxon index indicated that 27 of the 28 communities were phylogenetically clustered. These results suggest that species colonization and habitat filtering may have contributed to the current plant diversity of the Kunlun Mountains via ecological and evolutionary processes, and habitat filtering may play an important role in this ecological process.

By transferring the judgment of convex functions of several variables into the judgment of convex functions of one variable, the authors discuss the convexity of some convex functions of several variables.

Abstract Background Knee osteoarthritis (KOA) is one of the most common musculoskeletal disorders. Acupotomy may be effective for KOA, but the evidence is limited. This trial aims to determine the effectiveness and safety of acupotomy for KOA. Methods/design This is a parallel-group, assessor-blinded randomized controlled trial. Two hundred patients with KOA will be recruited and randomly assigned to two groups (group A or group D) in a 1:1 ratio. Patients in group A will receive acupotomy and topical diclofenac diethylamine for 4 weeks, while patients in group D will receive topical diclofenac diethylamine alone for 4 weeks. The primary outcome will be the response rate—the proportion of patients who achieve the minimal clinically important improvement in pain and function at week 4 compared with baseline. Secondary outcomes will include pain, function, quality of life, the use of rescue medicine (loxoprofen sodium), and adverse events at weeks 4, 8, and 24 after randomization. Besides, joint fluid and serum will be collected to assess the level of inflammatory cytokines, like TNF-α, IL-1β, and MMP-3. Discussion This study will contribute to a better understanding of the effectiveness and safety of acupotomy in combination with topical nonsteroidal anti-inflammatory drugs. If the hypothesis is confirmed, acupotomy may be recommended as adjunctive therapy for patients with KOA. Results of the study will be of great importance for the guidelines of clinical therapy. Trial registration Chinese Clinical Trial Registry ChiCTR2100043005 Registered on 4 February 2021.

Objective To evaluate 4Rs principle applied in animal experiments for research and to optimize training outcomes with animal model. Methods The 4Rs principle was applied in four parts of training process with animal models including “replacing animal experiments with human physiological experiments” “integrating experimental projects, reducing the use of animals” “optimizing experimental process for minimizing animal suffering” and “strengthening ethical concepts, responsibility in research with experimental animals”. After class, feedbacks from students were collected through questionnaire survey and the data was analyzed. Results There were 92.0% medical students showed sympathize for the laboratory animals in the process of animal experiments; took care of the welfare of experimental animals while achieving training objectives. Conclusions The 4Rs principle provides a new idea and method for animal experiment and cultivates learners' animal ethics.

In this paper, we analyze various classes of Stepanov-p-almost periodic functions and Stepanov-p-almost automorphic functions (p>0). The class of Stepanov-p-almost periodic (automorphic) functions in norm (p>0) is also introduced and analyzed. Some structural results for the introduced classes of functions are clarified. We also provide several important theoretical examples, useful remarks and some new applications of Stepanov-p-almost periodic type functions to the abstract (impulsive) first-order differential inclusions and the abstract (impulsive) fractional differential inclusions.

As a powerful tool for models of quantum computing, q-calculus has drawn the attention of many researchers in the discipline of special functions. In this paper, we present new properties and characterize q-Bessel functions of the first kind using some identities of q-calculus. The results presented in this article help us to obtain new expression results related to q-special functions. New summation and integral representations for q-Bessel functions of the first kind are also established. A few examples are also provided to demonstrate the effectiveness of the proposed strategy.

The goal of this paper is to investigate the existence and uniqueness of pseudo S-asymptotically periodic mild solutions for a class of neutral fractional evolution equations with finite delay. We essentially use the fractional powers of closed linear operators, the semigroup theory and some classical fixed point theorems. Furthermore, we provide an example to illustrate the applications of our abstract results.

In the original article [...]

Since the celebrated Brouwer’s fixed point theorem and Banach contraction principle were established, the rapid growth of fixed point theory and its applications have led to a number of scholarly essays studying the importance of its promotion and application in nonlinear analysis, applied mathematical analysis, economics, game theory, integral and differential equations and inclusions, dynamic systems theory, signal and image processing, etc [...]

In the paper, the authors find a sufficient and necessary condition for the power-exponential function 1+1xαx to be a Bernstein function, derive closed-form formulas for the nth derivatives of the power-exponential functions 1+1xαx and (1+x)α/x, and present a closed-form formula of the partial Bell polynomials Bn,k(H0(x),H1(x),⋯,Hn−k(x)) for n≥k≥0, where Hk(x)=∫0∞eu−1−ueuuk−1e−xudu for k≥0 are completely monotonic on (0,∞).

In this paper, we analyze the Bohr ρ-almost periodic type sequences and the generalized ρ-almost periodic type sequences of the form F:I×X→Y, where ∅≠I⊆Zn, X and Y are complex Banach spaces and ρ is a general binary relation on Y. We provide many structural results, observations and open problems about the introduced classes of ρ-almost periodic sequences. Certain applications of the established theoretical results to the abstract Volterra integro-difference equations are also given.

Abstract Background The management of discharge COVID-19 patients with recurrent positive SARS-CoV-2 RNA is challenging. However, there are fewer scientific dissertations about the risk of recurrent positive. The aim of this study was to explore the relationship between SARS-COV-2 RNA positive duration (SPD) and the risk of recurrent positive. Methods This case–control multi-center study enrolled participants from 8 Chinese hospital including 411 participants (recurrent positive 241). Using unadjusted and multivariate-adjusted logistic regression analyses, generalized additive model with a smooth curve fitting, we evaluated the associations between SPD and risk of recurrent positive. Besides, subgroup analyses were performed to explore the potential interactions. Results Among recurrent positive patients, there were 121 females (50.2%), median age was 50 years old [interquartile range (IQR): 38–63]. In non-adjusted model and adjusted model, SPD was associated with an increased risk of recurrent positive (fully-adjusted model: OR = 1.05, 95% CI: 1.02–1.08, P = 0.001); the curve fitting was not significant (P = 0.286). Comparing with SPD 28 days was risen substantially (OR = 3.09, 95% CI: 1.44–6.63, P = 0.004). Interaction and stratified analyses showed greater effect estimates of SPD and risk of recurrent positive in the hypertension, low monocyte count and percentage patients (P for interaction = 0.008, 0.002, 0.036, respectively). Conclusion SPD was associated with a higher risk of recurrent positive and especially SPD > 28 day had a two-fold increase in the relative risk of re-positive as compared with SPD

The recovery of spinal cord injury (SCI) is closely associated with the obstruction of oligodendrocyte progenitor cell (OPC) differentiation, which ultimately induces the inability to generate newly formed myelin. To address the concern, drug-based methods may be the most practical and feasible way, possibly applying to clinical therapies for patients with SCI. In our previous study, we found that clemastine treatment preserves myelin integrity, decreases the loss of axons, and improves functional recovery in the SCI model. Clemastine acts as an antagonist of the muscarinic acetylcholine receptor (muscarinic receptor, MR) identified from a string of anti-muscarinic drugs that can enhance oligodendrocyte differentiation and myelin wrapping. However, the effects of clemastine on OPC differentiation through MRs in SCI and the underlying mechanism remain unclear. To explore the possibility, a rat model of SCI was established. To investigate if clemastine could promote the differentiation of OPCs in SCI via MR, the expressions of OPC and mature OL were detected at 7 days post injury (dpi) or at 14 dpi. The significant effect of clemastine on encouraging OPC differentiation was revealed at 14 dpi rather than 7 dpi. Under pre-treatment with the MR agonist cevimeline, the positive role of clemastine on OPC differentiation was partially disrupted. Further studies indicated that clemastine increased the phosphorylation level of extracellular signal–regulated kinase 1/2 (p-ERK1/2) and the expressions of transcription factors, Myrf and Olig2. To determine the relationship among clemastine, ERK1/2 signaling, specified transcription factors, and OPC differentiation, the ERK1/2 signaling was disturbed by U0126. The inhibition of ERK1/2 in SCI rats treated with clemastine decreased the expressions of p-ERK 1/2, Myrf, Olig2, and mature OLs, suggesting that ERK1/2 is required for clemastine on promoting OPC differentiation and that specified transcription factors may be affected by the activity of ERK1/2. Moreover, the impact of clemastine on modulating the level of p-ERK 1/2 was restricted following cevimeline pre-injecting, which provides further evidence that the role of clemastine was mediated by MRs. Altogether, our data demonstrated that clemastine, mediated by MRs, promotes OPC differentiation under the enhancement of Myrf and Olig2 by activating ERK1/2 signaling and suggests a novel therapeutic prospect for SCI recovery.