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The syndrome of multiple morphological abnormalities of the sperm flagella (MMAF) is a specific kind of asthenoteratozoospermia with a mosaic of flagellar morphological abnormalities (absent, short, bent, coiled, and irregular flagella). MMAF was proposed in 2014 and has attracted increasing attention; however, it has not been clearly understood. In this review, we elucidate the definition of MMAF from a systematical view, the difference between MMAF and other conditions with asthenoteratozoospermia or asthenozoospermia (such as primary mitochondrial sheath defects and primary ciliary dyskinesia), the knowledge regarding its etiological mechanism and related genetic findings, and the clinical significance of MMAF for intracytoplasmic sperm injection and genetic counseling. This review provides the basic knowledge for MMAF and puts forward some suggestions for further investigations.

Background The purpose of this study was to perform an updated meta-analysis to compare the outcomes of kinematic alignment (KA) and mechanical alignment (MA) in patients undergoing total knee arthroplasty. Methods PubMed, EMBASE, Web of Science, Google Scholar, and the Cochrane Library were systematically searched. Eligible randomized controlled trials regarding the clinical outcomes of patients undergoing total knee arthroplasty with KA and MA were included for the analysis. Results A total of 1112 participants were included in this study, including 559 participants with KA and 553 patients with MA. This study revealed that the Western Ontario and McMaster Universities Osteoarthritis Index, Knee Society Score (knee and combined), and knee flexion range were better in the patients with kinematic alignment than in the mechanical alignment. In terms of radiological results, the femoral knee angle, mechanical medial proximal tibial angle, and joint line orientation angle were significantly different between the two techniques. Perioperatively, the walk distance before discharge was longer in the KA group than in the MA group. In contrast, other functional outcomes, radiological results, perioperative outcomes, and postoperative complication rates were similar in both the kinematic and mechanical alignment groups. Conclusions The KA technique achieved better functional outcomes than the mechanical technique in terms of KSS (knee and combined), WOMAC scores, and knee flexion range. PROSPERO trial registration number CRD42021264519. Date registration: July 28, 2021.

As the world’s largest emitter of carbon, China has implemented a series of environmental regulatory policies to reduce emissions. However, most of these environmental regulations have been at the expense of increased corporate environmental costs. Therefore, research on how to efficiently control these costs is of significant practical importance. This paper uses the China’s carbon trading policy (CTP) implemented in 2013 as a quasi-natural experiment, utilizing data from Chinese listed manufacturing firms between 2008 and 2020. Employing a difference-in-differences (DID) model, the study investigates the impact of market-incentive environmental regulatory policies (ERP) on environmental costs. The findings reveal that CTP significantly reduced the environmental costs of firms, confirming the positive and vital role market-incentive ERP can play in environmental protection and cost control. These conclusions remain robust after a series of stability tests. Mechanism analysis suggests that the cost reductions brought by market-incentive ERP are primarily achieved through increasing green innovation. Heterogeneity analysis shows that non-state-owned enterprises (non-SOEs), key polluting firms, firms with lower financial constraints, and firms with lower total production efficiency benefit more from market-incentive environmental regulatory policies. This study provides new empirical evidence for government policy-making aimed at achieving long-term sustainable development.

In the realm of cancer research, the tumor microenvironment (TME) plays a crucial role in tumor initiation and progression, shaped by complex interactions between cancer cells and surrounding non-cancerous cells. Cytokines, as essential immunomodulatory agents, are secreted by various cellular constituents within the TME, including immune cells, cancer-associated fibroblasts, and cancer cells themselves. These cytokines facilitate intricate communication networks that significantly influence tumor initiation, progression, metastasis, and immune suppression. Pyroptosis contributes to TME remodeling by promoting the release of pro-inflammatory cytokines and sustaining chronic inflammation, impacting processes such as immune escape and angiogenesis. However, challenges remain due to the complex interplay among cytokines, pyroptosis, and the TME, along with the dual effects of pyroptosis on cancer progression and therapy-related complications like cytokine release syndrome. Unraveling these complexities could facilitate strategies that balance inflammatory responses while minimizing tissue damage during therapy. This review delves into the complex crosstalk between cytokines, pyroptosis, and the TME, elucidating their contribution to tumor progression and metastasis. By synthesizing emerging therapeutic targets and innovative technologies concerning TME, this review aims to provide novel insights that could enhance treatment outcomes for cancer patients.

This study aims to explore the effect of hypertension on disease progression and prognosis in patients with coronavirus disease 2019 (COVID-19). A total of 310 patients diagnosed with COVID-19 were studied. A comparison was made between two groups of patients, those with hypertension and those without hypertension. Their demographic data, clinical manifestations, laboratory indicators, and treatment methods were collected and analyzed. A total of 310 patients, including 113 patients with hypertension and 197 patients without hypertension, were included in the analysis. Compared with patients without hypertension, patients with hypertension were older, were more likely to have diabetes and cerebrovascular disease, and were more likely to be transferred to the intensive care unit. The neutrophil count and lactate dehydrogenase, fibrinogen, and D-dimer levels in hypertensive patients were significantly higher than those in nonhypertensive patients (P < 0.05). However, multivariate analysis (adjusted for age and sex) failed to show that hypertension was an independent risk factor for COVID-19 mortality or severity. COVID-19 patients with hypertension were more likely than patients without hypertension to have severe pneumonia, excessive inflammatory reactions, organ and tissue damage, and deterioration of the disease. Patients with hypertension should be given additional attention to prevent worsening of their condition.

Background Periprosthetic joint infection (PJI) is a catastrophic complication after total hip arthroplasty (THA). Our meta-analysis aimed to identify the individual-related risk factors that predispose patients to PJI following primary THA. Methods Comprehensive literature retrieval from Pubmed, Web of Science, and the Cochrane Library was performed from inception to Feb 20th, 2021. Patient-related risk factors were compared as per the modifiable factors (BMI, smoke and alcohol abuse), non-modifiable factors (gender, age), and medical history characteristics, such as diabetes mellitus (DM), avascular necrosis (AVN) of femoral head, femoral neck fracture, rheumatoid arthritis (RA), cardiovascular disease (CVD), and osteoarthritis (OA) etc. The meta-analysis was applied by using risk ratios with 95% corresponding intervals. Sensitivity analysis and publication bias were performed to further assess the credibility of the results. Results Overall, 40 studies with 3,561,446 hips were enrolled in our study. By implementing cumulative meta-analysis, higher BMI was found associated with markedly increased PJI risk after primary THA [2.40 (2.01–2.85)]. Meanwhile, medical characteristics including DM [1.64 (1.25–2.21)], AVN [1.65 (1.07–2.56)], femoral neck fracture [1.75 (1.39–2.20)], RA [1.37 (1.23–1.54)], CVD [1.34 (1.03–1.74)], chronic pulmonary disease (CPD) [1.22 (1.08–1.37)], neurological disease [1.19 (1.05–1.35)], opioid use [1.53 (1.35–1.73)] and iron-deficiency anemia (IDA) [1.15 (1.13–1.17)] were also significantly correlated with higher rate of PJI. Conversely, dysplasia or dislocation [0.65 (0.45–0.93)], and OA [0.70 (0.62–0.79)] were protective factors. Of Note, female gender was protective for PJI only after longer follow-up. Besides, age, smoking, alcohol abuse, previous joint surgery, renal disease, hypertension, cancer, steroid use and liver disease were not closely related with PJI risk. Conclusion Our finding suggested that the individual-related risk factors for PJI after primary THA included high BMI, DM, AVN, femoral neck fracture, RA, CVD, CPD, neurological disease, opioid use and IDA, while protective factors were female gender, dysplasia/ dislocation and OA.

Pediatric cancers are the driving cause of death for children and adolescents. Due to safety requirements and considerations, treatment strategies and drugs for pediatric cancers have been so far scarcely studied. It is well known that tumor cells tend to progressively evade cell death pathways, which is known as apoptosis resistance, one of the hallmarks of cancer, dominating tumor drug resistance. Recently, treatments targeting nonapoptotic cell death have drawn great attention. Pyroptosis, a newly specialized form of cell death, acts as a critical physiological regulator in inflammatory reaction, cell development, tissue homeostasis and stress response. The action in different forms of pyroptosis is of great significance in the therapy of pediatric cancers. Pyroptosis could be induced and consequently modulate tumorigenesis, progression, and metastasis if treated with local or systemic therapies. However, excessive or uncontrolled cell death might lead to tissue damage, acute inflammation, or even cytokine release syndrome, which facilitates tumor progression or recurrence. Herein, we aimed to describe the molecular mechanisms of pyroptosis, to highlight and discuss the challenges and opportunities for activating pyroptosis pathways through various oncologic therapies in multiple pediatric neoplasms, including osteosarcoma, neuroblastoma, leukemia, lymphoma, and brain tumors.

Advances in mass spectrometry accelerates the characterization of HLA ligandome, necessitating the development of efficient methods for immunopeptidomics analysis and (neo)antigen prediction. We develop ImmuneApp, an interpretable deep learning framework trained on extensive HLA ligand datasets, which improves the prediction of HLA-I epitopes, prioritizes neoepitopes, and enhances immunopeptidomics deconvolution. ImmuneApp extracts informative embeddings and identifies key residues for pHLA binding. We also present a more accurate model-based deconvolution approach and systematically analyzed 216 multi-allelic immunopeptidomics samples, identifying 835,551 ligands restricted to over 100 HLA-I alleles. Our investigation reveals the effectiveness of the composite model, denoted as ImmuneApp-MA, which integrates mono- and multi-allelic data to enhance predictive performance. Leveraging ImmuneApp-MA as a pre-trained model, we built ImmuneApp-Neo, an immunogenicity predictor that outperforms existing methods for prioritizing immunogenic neoepitope. ImmuneApp demonstrates its utility across various immunopeptidomics datasets, which will promote the discovery of novel neoantigens and the development of new immunotherapies. The identification of HLA epitopes is essential for vaccine and immunotherapy development. Here, authors develop ImmuneApp using deep learning on extensive immunopeptidomics data, advancing antigen presentation prediction, neoepitope prioritisation, and immunopeptidomics deconvolution.

While lymphocytopenia is a common characteristic of coronavirus disease 2019 (COVID-19), the mechanisms responsible for this lymphocyte depletion are unclear. Here, we retrospectively reviewed the clinical and immunological data from 18 fatal COVID-19 cases, results showed that these patients had severe lymphocytopenia, together with high serum levels of inflammatory cytokines (IL-6, IL-8 and IL-10), and elevation of many other mediators in routine laboratory tests, including C-reactive protein, lactate dehydrogenase, α-hydroxybutyrate dehydrogenase and natriuretic peptide type B. The spleens and hilar lymph nodes (LNs) from six additional COVID-19 patients with post-mortem examinations were also collected, histopathologic detection showed that both organs manifested severe tissue damage and lymphocyte apoptosis in these six cases. In situ hybridization assays illustrated that SARS-CoV-2 viral RNA accumulates in these tissues, and transmission electronic microscopy confirmed that coronavirus-like particles were visible in the LNs. SARS-CoV-2 Spike and Nucleocapsid protein (NP) accumulated in the spleens and LNs, and the NP antigen restricted in angiotensin-converting enzyme 2 (ACE2) positive macrophages and dendritic cells (DCs). Furthermore, SARS-CoV-2 triggered the transcription of Il6 , Il8 and Il1b genes in infected primary macrophages and DCs in vitro , and SARS-CoV-2-NP + macrophages and DCs also manifested high levels of IL-6 and IL-1β, which might directly decimate human spleens and LNs and subsequently lead to lymphocytopenia in vivo . Collectively, these results demonstrated that SARS-CoV-2 induced lymphocytopenia by promoting systemic inflammation and direct neutralization in human spleen and LNs.

Diabetic microangiopathy is among the most common complications affecting patients with diabetes, and includes both diabetic retinopathy (DR) and diabetic nephropathy (DKD). Diabetic microangiopathy remains a persistent threat to the health and quality of life of affected patients. Mechanistically, the severity of DR and DKD is tied to mitochondrial and glucose metabolism abnormalities, with the activation of the glycolytic enzyme pyruvate kinase M2 (PKM2) contributing to mitochondrial and glomerular dysfunction, abnormal renal hemodynamics, and retinopathy. PKM2 can activate inflammatory bodies in macrophages to promote the release of inflammatory mediators, and serves as a key regulator of inflammatory factors, chemokines and adhesion molecules. As such, there is sufficient evidence that PKM2 can be used as a biomarker for the diagnosis of diabetes and diabetic microangiopathy. Here, we survey the mechanisms whereby PKM2 contributes to diabetes-related microvascular diseases, associated regulatory roles, post-translational modifications, and the potential utility of PKM2 as a therapeutic target. Through this literature review, we have determined that PKM2 offers promise as both a diagnostic marker and therapeutic target with direct relevance to research pertaining to diabetic microangiopathy.