Diagnostic Value of SAA Levels and Perianal Symptoms in the Complicated Perianal Abscesses Among Mpox-Infected Patients.

Objective: Precise prediction of the occurrence of complicated perianal abscesses (PAs) in monkeypox (mpox)-infected patients is important for therapeutic optimization. This study sought to identify risk factors of complicated PA. Methods: A total of 48 patients with mpox infection (PA group, n = 10; non-PA (NPA) group, n = 38) were enrolled in our study, who were hospitalized in Hangzhou Xixi Hospital, China from 29 June to 3 September 2023. The data of demographic characteristics, and clinical symptoms, serum SAA, PCT, CRP, and IL-6 levels were collected by the Electronic Medical Record. The diagnostic values of these biomarkers were assessed using multivariate logistic regression and ROC curve analyses. Results: A decrease in serum IL-6, SAA, and CRP levels (all p-value < 0.05), but not PCT, was observed in all mpox-infected patients. A significant positive correlation was also noted between IL-6, SAA, CRP, and PCT levels (all p-value < 0.05). There was a significant increase in IL-6 and SAA levels and the SAA/CRP ratio in serum samples from patients in the PA group. Multivariate logistic regression and ROC curve analyses identified that the combined use of perianal symptoms and SAA was more sensitive than perianal symptoms or SAA alone as predictors of complicated PA. This combination had the highest predictive value for disease progression, with an AUC of 0.920 (p-value < 0.001). Conclusion: The combination of perianal symptoms and SAA levels was strongly linked to the occurrence of complicated PA in mpox-infected patients. These findings may inform the early diagnosis of this patient population.

Type 2 herpes simplex virus-induced anti-N-methyl-D-aspartate receptor encephalitis responsive to immunoglobulin monotherapy.

Herpes simplex virus-2 encephalitis (HSV2E) in immunocompetent adults is exceptionally rare, and the subsequent onset of autoimmune encephalitis after HSV2E is even less common. This report presents the inaugural Chinese case of anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) induced by HSV2E, confirmed via metagenomic next-generation sequencing (mNGS). The patient demonstrated a favorable response to intravenous immunoglobulin (IVIG) monotherapy. This case emphasizes the importance of considering autoimmune encephalitis in patients exhibiting new or recurrent neurological symptoms after HSV2E recovery. Comprehensive mNGS and neuronal antibody testing are essential for timely diagnosis. Moreover, IVIG monotherapy can serve as an effective treatment for NMDARE induced by HSV2, providing a viable alternative, particularly when steroid therapy is contraindicated.

Current and promising applications of MOF composites in the healing of diabetes wounds.

Diabetes mellitus is an exponentially growing chronic metabolic disease identified by prolonged hyperglycemia that leads to a plethora of health problems. It is well established that the skin of diabetic patients is more prone to injury, and hence, wound healing is an utmost critical restorative process for injured skin and other tissues. Diabetes patients have problems with wound healing at all stages, which ultimately results in delays in the healing process. Therefore, it is vital to find new medications or techniques to hasten the healing of wounds. Metal-organic frameworks (MOFs), an assorted class of porous hybrid materials comprising metal ions coordinated to organic ligands, can display great potential in accelerating diabetic wound healing due to their good physicochemical properties. The release of metal ions during the degradation of MOFs can promote the differentiation of fibroblasts into myofibroblasts and subsequently angiogenesis. Secondly, similar to enzyme-like active substances, they can eliminate reactive oxygen species (ROS) overproduction (secondary to the bio-load of wound bacteria), which is conducive to accelerating diabetic wound healing. Subsequently, MOFs can support the slow release of drugs (molecular or gas therapeutics) in diabetic wounds and promote wound healing by regulating pathological signaling pathways in the wound microenvironment or inhibiting the expression of inflammatory factors. In addition, the combination of photodynamic and photothermal therapies using photo-stimulated porphyrin-based MOF nanosystems has brought up a new idea for treating complicated diabetic wound microenvironments. In this review, recent advances affecting diabetic wound healing, current means of rapid diabetic wound healing, and the limitations of traditional approaches are discussed. Further, the diabetic wound healing applications of MOFs have been discussed followed by the future challenges and directions of MOF materials in diabetic wound healing.

Enantioselective Synthesis of Oxazocines via MQ-Phos Enabled Palladium-Catalyzed Asymmetric Formal [4+4]-Cycloadditions.

Oxazocines are key structural intermediates in the synthesis of natural products and pharmaceutical molecules. However, the synthesis of oxazocines especially in a highly enantioselective manner, is a long-standing formidable challenge due to unfavorable energetics involved in cyclization. Herein, a series of new PNP-Ligand P-chiral stereocenter is first designed and synthesized, called MQ-Phos, and successfully applied it in the Pd-catalyzed enantioselective higher-order formal [4+4]-cycloaddition of α, ß-unsaturated imines with 2-(hydroxymethyl)-1-arylallyl carbonates. The reaction features mild conditions, excellent regio- and enantiocontrol and a broad substrate scope (54 examples). Various medium-sized rings can be afforded in moderate to excellent yields (up to 92%) and excellent enantioselectivity (up to 99% ee). The newly developed MQ-Phos is critical for synthesis of the medium-sized ring in excellent catalytic reactivity and enantioselectivity.

Advances in drug delivery-based therapeutic strategies for renal fibrosis treatment.

Renal fibrosis is the result of all chronic kidney diseases and is becoming a major global health hazard. Currently, traditional treatments for renal fibrosis are difficult to meet clinical needs due to shortcomings such as poor efficacy or highly toxic side effects. Therefore, therapeutic strategies that target the kidneys are needed to overcome these shortcomings. Drug delivery can be attained by improving drug stability and addressing controlled release and targeted delivery of drugs in the delivery category. By combining drug delivery technology with nanosystems, controlled drug release and biodistribution can be achieved, enhancing therapeutic efficacy and reducing toxic cross-wise effects. This review discusses nanomaterial drug delivery strategies reported in recent years. Firstly, the present review describes the mechanisms of renal fibrosis and anti-renal fibrosis drug delivery. Secondly, different nanomaterial drug delivery strategies for the treatment of renal injury and fibrosis are highlighted. Finally, the limitations of these strategies are also discussed. Investigating various anti-renal fibrosis drug delivery strategies reveals the characteristics and therapeutic effects of various novel nanosystem-derived drug delivery approaches. This will serve as a reference for future research on drug delivery strategies for renal fibrosis treatment.

Non-Invasive Self-Adaptive Information States' Acquisition inside Dynamic Scattering Spaces.

Pushing the information states' acquisition efficiency has been a long-held goal to reach the measurement precision limit inside scattering spaces. Recent studies have indicated that maximal information states can be attained through engineered modes; however, partial intrusion is generally required. While non-invasive designs have been substantially explored across diverse physical scenarios, the non-invasive acquisition of information states inside dynamic scattering spaces remains challenging due to the intractable non-unique mapping problem, particularly in the context of multi-target scenarios. Here, we establish the feasibility of non-invasive information states' acquisition experimentally for the first time by introducing a tandem-generated adversarial network framework inside dynamic scattering spaces. To illustrate the framework's efficacy, we demonstrate that efficient information states' acquisition for multi-target scenarios can achieve the Fisher information limit solely through the utilization of the external scattering matrix of the system. Our work provides insightful perspectives for precise measurements inside dynamic complex systems.

MOF-Based Platform for Kidney Diseases: Advances, Challenges, and Prospects.

Kidney diseases are important diseases that affect human health worldwide. According to the 2020 World Health Organization (WHO) report, kidney diseases have become the top 10 causes of death. Strengthening the prevention, primary diagnosis, and action of kidney-related diseases is of great significance in maintaining human health and improving the quality of life. It is increasingly challenging to address clinical needs with the present technologies for diagnosing and treating renal illness. Fortunately, metal-organic frameworks (MOFs) have shown great promise in the diagnosis and treatment of kidney diseases. This review summarizes the research progress of MOFs in the diagnosis and treatment of renal disease in recent years. Firstly, we introduce the basic structure and properties of MOFs. Secondly, we focus on the utilization of MOFs in the diagnosis and treatment of kidney diseases. In the diagnosis of kidney disease, MOFs are usually designed as biosensors to detect biomarkers related to kidney disease. In the treatment of kidney disease, MOFs can not only be used as an effective adsorbent for uremic toxins during hemodialysis but also as a precise treatment of intelligent drug delivery carriers. They can also be combined with nano-chelation technology to solve the problem of the imbalance of trace elements in kidney disease. Finally, we describe the current challenges and prospects of MOFs in the diagnosis and treatment of kidney diseases.

Developmental toxicity of the neonicotinoid pesticide clothianidin to the larvae of the crustacean Decapoda, Penaeus vannamei.

The developmental toxicity effects of neonicotinoid pesticides such as clothianidin have not been fully explored in agricultural applications. This is particularly noteworthy because such pesticides significantly impact the survival rates of invertebrates, with arthropod larvae being particularly vulnerable. This study aimed to address this research gap by specifically investigating the toxicological effects of clothianidin on the developmental stages of the larvae of the economically important aquaculture species Penaeus vannamei. In these experiments, shrimp eggs were exposed to seawater containing different concentrations of clothianidin beginning at N1, and each phase was observed and analyzed to determine its toxic impact on larval development. These results revealed that clothianidin induces an increase in deformity rates and triggers abnormal cell apoptosis. It also significantly reduced survival rates and markedly decreased body length and heart rate in the later stages of larval development (P3). Transcriptomic analysis revealed disruptions in larval DNA integrity, protein synthesis, and signal transduction caused by clothianidin. To survive prolonged exposure, larvae may attempt to maintain their viability by repairing cell structures and enhancing signal transduction mechanisms. This study offers the first empirical evidence of the toxicity of clothianidin to arthropod larvae, underscoring the impact of environmental pollution on aquatic health.

A C-type lectin with dual carbohydrate recognition domains functions in innate immune response in Asian corn borer, Ostrinia furnacalis.

C-type lectins (CTLs) act as pattern recognition receptors (PRRs) to initiate the innate immune response in insects. A CTL with dual carbohydrate recognition domains (CRDs) (named immulectin-4 [IML-4]) was selected from the Ostrinia furnacalis transcriptome dataset for functional studies. We cloned the full-length complementary DNA of O. furnacalis IML-4 (OfIML-4). It encodes a 328-residue protein with a Glu-Pro-Asn (EPN) and Gln-Pro-Asp (QPD) motifs in 2 CRDs, respectively. OfIML-4 messenger RNA levels increased significantly upon the bacterial and fungal infection. Recombinant OfIML-4 (rIML-4) and its individual CRDs (rCRD1 and rCRD2) exhibited the binding ability to various microorganisms including Escherichia coli, Micrococcus luteus, Pichia pastoris, and Beauveria bassiana, and the cell wall components including lipopolysaccharide from E. coli, peptidoglycan from M. luteus or Bacillus subtilis, and curdlan from Alcaligenes faecalis. The binding further induced the agglutination of E. coli, M. luteus, and B. bassiana in the presence of calcium, the phagocytosis of Staphylococcus aureus by the hemocytes, in vitro encapsulation and melanization of nickel-nitrilotriacetic acid beads, and a significant increase in phenoloxidase activity of plasma. In addition, rIML-4 significantly enhanced the phagocytosis, nodulation, and resistance of O. furnacalis to B. bassiana. Taken together, our results suggest that OfIML-4 potentially works as a PRR to recognize the invading microorganisms, and functions in the innate immune response in O. furnacalis.

Next-generation neonicotinoid: The impact of cycloxaprid on the crustacean decapod Penaeus vannamei.

Cycloxaprid, a new neonicotinoid pesticide, poses ecological risks, particularly in aquatic environments, due to its unique action and environmental dispersal. This study investigated the ecotoxicological effects of various concentrations of cycloxaprid on Penaeus vannamei over 28 days. High cycloxaprid levels significantly altered shrimp physiology, as shown by changes in the hepatosomatic index and fattening. Indicators of oxidative stress, such as increased serum hemocyanin, respiratory burst, and nitric oxide, as well as decreased phenol oxidase activity, were observed. Additionally, elevated activities of lactate dehydrogenase, succinate dehydrogenase, and isocitrate dehydrogenase indicated disrupted energy metabolism in the hepatopancreas. Notably, analyses of the nervous system revealed marked disturbances in neural signaling, as evidenced by elevated acetylcholine, octopamine, and acetylcholinesterase levels. Transcriptomic analysis highlighted significant effects on gene expression and metabolic processes in the hepatopancreas and nervous system. This study demonstrated that cycloxaprid disrupts neural signaling and oxidative balance in P. vannamei, potentially affecting its growth, and provides key insights into its biochemical and transcriptomic toxicity in aquatic systems.

Morphological and molecular analyses reveal two new species of Grifola (Polyporales) from Yunnan, China.

Species of Grifola are famous edible mushrooms and are deeply loved by consumers around the world. Most species of this genus have been described and recorded in Oceania, Europe and South America, with only Grifolafrondosa being recorded in Asia. In this study, two novel species of Grifola from southwestern China (Asia) are introduced. Macro and micromorphological characters are described. Grifolaedulissp. nov. present medium-size basidiomata with gray to gray-brown lobes upper surface, mostly tibiiform or narrowly clavate, rarely narrowly lageniform or ellipsoid chlamydospores, cuticle hyphae terminal segments slightly enlarged. Grifolasinensissp. nov. has white to grayish white lobes upper surface, mostly ellipsoid, rarely narrowly utriform chlamydospores, and broadly ellipsoid to ellipsoid basidiospores (4.6-7.9 × 3.0-5.9 µm). The two new species are supported by phylogenetic analyses of combined nuclear rDNA internal transcribed spacer ITS1-5.8S-ITS2 rDNA (ITS) and ß-tubulin (TUBB). Moreover, the genetic distance between TUBB sequences of those specimen from GenBank was 1.76-1.9%. Thus, the conspecificity relationship of our specimens remains uncertain, and further specimens are required to conclusively confirm its identity.

Early-stage neutralizing antibody level associated with the re-positive risk of Omicron SARS-CoV-2 RNA in patients recovered from COVID-19.

Post-discharge re-positivity of Omicron SARS-CoV-2 is challenging for the sufficient control of this pandemic. However, there are few studies about the risk of re-positivity. We aimed to explore the association of neutralizing antibodies (nAbs, AU/mL) with the incidence of re-positivity among patients recovered from COVID-19. A retrospective cohort study selected 318 Omicron-infected patients was conducted in China between December 2021 and April 2022. The peak value of nAb levels (nAb-peak) within 14 days of disease onset was defined as the baseline and was mainly used for the subsequent analyses. In the unadjusted, minimally adjusted, fully adjusted, and additionally adjusted for IgG models, a per-standard deviation (SD) increase in the nAb-peak values was significantly associated with a 59 %, 59 %, 50 %, and 75 % decreased risk of Omicron SARS-CoV-2 re-positivity during post-discharge surveillance, respectively. Stratified analyses showed no significant changes in the relationship between nAbs and re-positivity. Our study suggested that the increase in baseline nAb levels independently associated with a low risk of re-positivity in patients recovered from COVID-19.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): contemporary advances and current controversies.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory syndrome with characteristic clinical, radiological, and pathological features, and can be effectively treated with corticosteroid-based immunotherapies. The exact pathogenesis of CLIPPERS remains unclear, and specific diagnostic biomarkers are not available. According to the 2017 diagnostic criteria, probable CLIPPERS should be considered in middle-aged patients with subacute onset of pontocerebellar symptoms and typical punctuate and curvilinear gadolinium enhancement lesions ("salt-and-pepper" appearance) located in the hindbrain (especially pons) on magnetic resonance imaging. In addition, CLIPPERS-mimics, such as central nervous system (CNS) lymphoma, and several antibody-associated autoimmune CNS diseases (e.g., myelin oligodendrocyte glycoprotein antibody-associated disease, autoimmune glial fibrillary acidic protein astrocytopathy, and anti-N-methyl-D-aspartate receptor encephalitis), should be extensively excluded. The prerequisite for definite CLIPPERS is the perivascular T-cell-predominant inflammatory infiltration observed on pathological analysis. A biopsy is strongly suggested when clinical/radiological red flags are present. Most patients with CLIPPERS respond well to corticosteroids and have a good prognosis. Long-term low-dose corticosteroid maintenance therapy or corticosteroids coupled with immunosuppressants are recommended to prevent the recurrence of the syndrome. The potential progression of CLIPPERS to lymphoma has been suggested in some cases; therefore, at least 2-year clinical and radiological follow-up is essential. Here, we critically review the recent developments and provided an update on the clinical characteristics, diagnostic criteria, differential diagnoses, and therapeutic management of CLIPPERS. We also discuss the current controversies in this context that can be resolved in future research studies.

Myelin oligodendrocyte glycoprotein antibody and N-methyl-d-aspartate receptor antibody overlapping syndrome: insights from the recent case reports.

The overlapping of two or more types of neural autoantibodies in one patient has increasingly been documented in recent years. The coexistence of myelin oligodendrocyte glycoprotein (MOG) and N-methyl-d-aspartate receptor (NMDAR) antibodies is most common, which leads to a unique condition known as the MOG antibody and NMDAR antibody overlapping syndrome (MNOS). Here, we have reviewed the pathogenesis, clinical manifestations, paraclinical features, and treatment of MNOS. Forty-nine patients with MNOS were included in this study. They were young males with a median onset age of 23 years. No tumors were observed in the patients, and 24 of them reported prodromal symptoms. The most common clinical presentations were psychiatric symptoms (35/49) and seizures (25/49). Abnormalities on magnetic resonance imaging involved the brainstem (11/49), cerebellum (9/49), and parietal lobe (9/49). Most patients mostly responded to immunotherapy and had a good long-term prognosis. However, the overall recurrence rate of MNOS was higher than that of mono antibody-positive diseases. The existence of concurrent NMDAR antibodies should be suspected in patients with MOG antibody-associated disease having psychiatric symptoms, seizures, movement disorders, or autonomic dysfunction. Similarly, serum MOG antibody testing should be performed when patients with anti-NMDAR encephalitis present with atypical clinical manifestations, such as visual impairment and limb weakness, and neuroradiological findings, such as optic nerve, spinal cord, or infratentorial involvement or meningeal enhancement. Early detection of the syndrome and prompt treatment can be beneficial for these patients, and maintenance immunosuppressive therapy is recommended due to the high overall recurrence rate of the syndrome.

Development and Evaluation of a Nomogram for Predicting the Outcome of Immune Reconstitution Among HIV/AIDS Patients Receiving Antiretroviral Therapy in China.

This study aims to develop and evaluate a model to predict the immune reconstitution among HIV/AIDS patients after antiretroviral therapy (ART). A total of 502 HIV/AIDS patients are randomized to the training cohort and evaluation cohort. Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analysis are performed to identify the indicators and establish the nomogram for predicting the immune reconstitution. Decision curve analysis (DCA) and clinical impact curve (CIC) are used to evaluate the clinical effectiveness of the nomogram. Predictive factors included white blood cells (WBC), baseline CD4+ T-cell counts (baseline CD4), ratio of effector regulatory T cells to resting regulatory T cells (eTreg/rTreg) and low-density lipoprotein cholesterol (LDL-C) and are incorporated into the nomogram. The area under the curve (AUC) is 0.812 (95% CI, 0.767∼0.851) and 0.794 (95%CI, 0.719∼0.857) in the training cohort and evaluation cohort, respectively. The calibration curve shows a high consistency between the predicted and actual observations. Moreover, DCA and CIC indicate that the nomogram has a superior net benefit in predicting poor immune reconstitution. A simple-to-use nomogram containing four routinely collected variables is developed and internally evaluated and can be used to predict the poor immune reconstitution in HIV/AIDS patients after ART.

Recent advances in ligand-enabled palladium-catalyzed divergent synthesis.

Developing efficient and straightforward strategies to rapidly construct structurally distinct and diverse organic molecules is one of the most fundamental tasks in organic synthesis, drug discovery and materials science. In recent years, divergent synthesis of organic functional molecules from the same starting materials has attracted significant attention and has been recognized as an efficient and powerful strategy. To achieve this objective, the proper adjustment of reaction conditions, such as catalysts, solvents, ligands, etc., is required. In this review, we summarized the recent efforts in chemo-, regio- and stereodivergent reactions involving acyclic and cyclic systems catalyzed by palladium complexes. Meanwhile, the reaction types, including carbonylative reactions, coupling reactions and cycloaddition reactions, as well as the probable mechanism have also been highlighted in detail.

Recent Advances in Palladium-Catalyzed [4 + n] Cycloaddition of Lactones, Benzoxazinanones, Allylic Carbonates, and Vinyloxetanes.

Palladium-catalyzed allylation cyclization reaction has recently emerged as an efficient and powerful synthetic platform for the construction of diverse and valuable carbo- and heterocycles. Thus the development of new allylic motifs for achieving this type of transformations in high reactivity and selectivity is of great importance. Generally, these substrates have been utilized as 1,3-, 1,4-, 1,5-, 1,6-dipoles in many reactions, which are applied to prepare highly functionalized products with complete control of chemo-, regio-, diastereo-, and enantioselectivity. In this review, we focus our attention on the development of palladium-catalyzed [4 + n] cycloaddition of allylic motifs and describe a comprehensive and impressive advances in this area. Meanwhile, the related mechanism and the application of these annulation strategies in natural product total synthesis will be highlighted in detail.

Anti-adenylate kinase 5 encephalitis: Clinical characteristics, diagnosis, and management of this rare entity.

The spectrum and understanding of antibody-positive autoimmune encephalitis (AE) have expanded over the past few decades. In 2007, a rare subtype of AE known as anti-adenylate kinase 5 (AK5) encephalitis, was first reported. This disease is more common in elderly males, with limbic encephalitis as the core phenotype (characterized by subacute anterograde amnesia, sometimes with psychiatric symptoms, and rarely with seizures). Brain magnetic resonance imaging typically demonstrated initial temporal lobe T2/fluid-attenuated inversion recovery hyperintensities, and subsequent atrophy. No concomitant tumors have been found yet. AK5 antibody, targeting the intracellular antigen, is a biomarker for a non-paraneoplastic T-cell autoimmunity response, and can be detected in serum and cerebrospinal fluid using tissue-based and cell-based assays. Cytotoxic T-cell-mediating neuronal injury and loss play a pivotal role in the immunopathogenesis of anti-AK5 encephalitis. Patients mostly show poor response to immunotherapy and thus a poor prognosis in the long run. Herein, we review the literature and provide updated knowledge of this less-known entity, focusing on clinical characteristics, paraclinical findings, diagnosis process, and therapeutic approaches.

A rare BCR-ABL1 transcript in chronic myeloid leukemia: Case report and literature review.

BACKGROUND: The purpose of this report is to enhance our scientific understanding of the clinicopathologic features of chronic myeloid leukemia (CML) with the e12a3 transcript and to provide insights into potential treatment options for this rare subtype of CML. CASE SUMMARY: We present the case of a 21-year-old Chinese male patient who was diagnosed with chronic myeloid leukemia (CML) with the e12a3 transcript. Biopsy of his left iliac soft tissue mass indicated that he was in the blast crisis phase of CML. The patient was treated with tyrosine kinase inhibitor (TKI) drugs and achieved remission, but relapsed soon after. Despite receiving prognostic chemotherapy, the disease progressed and eventually led to the patient's death. CONCLUSION: To avoid missed diagnosis and misdiagnosis, it is recommended to conduct a thorough clinical evaluation and actively identify the underlying etiology.