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Abstract The Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 system, a groundbreaking innovation in genetic engineering, has revolutionized our approach to surmounting complex diseases, culminating in CASGEVY™ approved for sickle cell anemia. Derived from a microbial immune defense mechanism, CRISPR/Cas9, characterized as precision, maneuverability and universality in gene editing, has been harnessed as a versatile tool for precisely manipulating DNA in mammals. In the process of applying it to practice, the consecutive exploitation of novel orthologs and variants never ceases. It’s conducive to understanding the essentialities of diseases, particularly cancer, which is crucial for diagnosis, prevention, and treatment. CRISPR/Cas9 is used not only to investigate tumorous genes functioning but also to model disparate cancers, providing valuable insights into tumor biology, resistance, and immune evasion. Upon cancer therapy, CRISPR/Cas9 is instrumental in developing individual and precise cancer therapies that can selectively activate or deactivate genes within tumor cells, aiming to cripple tumor growth and invasion and sensitize cancer cells to treatments. Furthermore, it facilitates the development of innovative treatments, enhancing the targeting efficiency of reprogrammed immune cells, exemplified by advancements in CAR-T regimen. Beyond therapy, it is a potent tool for screening susceptible genes, offering the possibility of intervening before the tumor initiative or progresses. However, despite its vast potential, the application of CRISPR/Cas9 in cancer research and therapy is accompanied by significant efficacy, efficiency, technical, and safety considerations. Escalating technology innovations are warranted to address these issues. The CRISPR/Cas9 system is revolutionizing cancer research and treatment, opening up new avenues for advancements in our understanding and management of cancers. The integration of this evolving technology into clinical practice promises a new era of precision oncology, with targeted, personalized, and potentially curative therapies for cancer patients.

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder characterized by abnormal protein deposition. With an alarming 30 million people affected worldwide, AD poses a significant public health concern. While inhibiting key enzymes such as β-site amyloid precursor protein-cleaving enzyme 1 and γ-secretase or enhancing amyloid-β clearance, has been considered the reasonable strategy for AD treatment, their efficacy has been compromised by ineffectiveness. Furthermore, our understanding of AD pathogenesis remains incomplete. Normal aging is associated with a decline in glucose uptake in the brain, a process exacerbated in patients with AD, leading to significant impairment of a critical post-translational modification: glycosylation. Glycosylation, a finely regulated mechanism of intracellular secondary protein processing, plays a pivotal role in regulating essential functions such as synaptogenesis, neurogenesis, axon guidance, as well as learning and memory within the central nervous system. Advanced glycomic analysis has unveiled that abnormal glycosylation of key AD-related proteins closely correlates with the onset and progression of the disease. In this context, we aimed to delve into the intricate role and underlying mechanisms of glycosylation in the etiopathology and pathogenesis of AD. By highlighting the potential of targeting glycosylation as a promising and alternative therapeutic avenue for managing AD, we strive to contribute to the advancement of treatment strategies for this debilitating condition.

Lung metastasis of breast cancer is rapidly becoming a thorny problem in the treatment of patients with breast cancer and an obstacle to long-term survival. The main challenges of treatment are the absence of therapeutic targets and drug resistance, which promotes the development of nanotechnology in the diagnosis and treatment process. Taking advantage of the controllability and targeting of nanotechnology, drug-targeted delivery, controlled sustained release, multi-drug combination, improved drug efficacy, and reduced side effects can be realized in the process of the diagnosis and treatment of metastatic breast cancer (MBC). Several nanotechnology-based theranostic strategies have been investigated in breast cancer lung metastases (BCLM): targeted drug delivery, imaging analysis, immunotherapy, gene therapy, and multi-modality combined therapy, and some clinical applications are in the research phase. In this review, we present current nanotechnology-based diagnosis and treatment approaches for patients of incurable breast cancer with lung metastases, and we hope to be able to summarize more effective and promising nano-drug diagnosis and treatment systems that aim to improve the survival of patients with advanced MBC. We describe nanoplatform-based experimental studies and clinical trials targeting the tumor and the tumor microenvironment (TME) for BCLM to obtain more targeted treatment and in the future treatment steps for patients to provide a pioneering strategy.

Abstract This study aims to investigate the mechanism of platelet activation‐induced thrombosis in patients with acute non‐ST segment elevation myocardial infarction (NSTEMI) by detecting the expression of autophagy‐associated proteins in platelets of patients with NSTEMI. A prospective study was conducted on 121 patients with NSTEMI who underwent emergency coronary angiography and optical coherence tomography. The participants were divided into two groups: the ST segment un‐offset group (n = 64) and the ST segment depression group (n = 57). We selected a control group of 60 patients without AMI during the same period. The levels of autophagy‐associated proteins and the expression of autophagy‐associated proteins in platelets were measured using immunofluorescence staining and Western blot. In NSTEMI, the prevalence of red thrombus was higher in the ST segment un‐offset myocardial infarction (STUMI) group, whereas white thrombus was more common in the ST segment depression myocardial infarction (STDMI) group. Furthermore, the platelet aggregation rate was significantly higher in the white thrombus group compared with the red thrombus group. Compared with the control group, the autophagy‐related protein expression decreased, and the expression of αIIbβ3 increased in NSTEMI. The overexpression of Beclin1 could activate platelet autophagy and inhibit the expression of αIIbβ3. The results suggested that the increase in platelet aggregation rate in patients with NSTEMI may be potentially related to the change in autophagy. And the overexpression of Beclin1 could reduce the platelet aggregation rate by activating platelet autophagy. Our findings demonstrated that Beclin1 could be a potential therapeutic target for inhibiting platelet aggregation in NSTEMI.

Introduction: Given the high prevalence of thyroid nodules and the potential for malignancy, it is imperative to understand the various factors that contribute to their development. This study aimed to explore the relationship between metabolic syndrome, lifestyle, and thyroid nodules in adult men in southern China. Methods: This study enrolled a total of 183,990 subjects at a medical examination center in a general hospital in southern China between January 1, 2015, and December 31, 2020. Multivariate logistic regression analysis was utilized to evaluate the relationship between metabolic syndrome, lifestyle factors, and thyroid nodules. Furthermore, structural equation modeling elucidated the intricate relationships among these variables. Results: The prevalence of thyroid nodules among Chinese adult males was 14.9%. Several factors were identified as risk factors for thyroid nodules, including advanced age, irregular meal time, smoking or quitting smoking, quitting drinking, heavy manual labor, hypertension, diabetes, dyslipidemia and centripetal obesity, and those belonging to ethnic minorities and drinking alcohol were found to be protective factors against thyroid nodules. Structural equation modeling highlighted metabolic syndrome's mediating role amidst lifestyle influences on thyroid nodules. Conclusion: The prevalence of thyroid nodules in Chinese adult males is relatively moderate to low. The factors identified in this study can help clinicians identify high-risk patients and develop targeted screening strategies for the timely detection of thyroid nodules. However, further mechanistic research and longitudinal studies are necessary to explore the underlying causes and establish causal relationships.

In order to obtain the higher expression of cannabinoid acid synthase (CBDAS) through the microbial chassis, the recombinant enzyme for the in vitro synthesis of cannabinoid (CBD) was studied. The CBDAS gene was firstly cloned from cannabis leaves with higher content of CBD, its basic physicochemical properties of proteins were then analyzed by bioinformatics methods. After construction of the recombinant plasmid pPIC9K-CBDAS and transformation into Pichia pastoris, conditions of the recombinant protein CBDAS were optimized and its catalytic activities were finally analyzed. The results indicated that the constructed pPIC9K-CBDAS fusion protein expression system could be successfully expressed in P. pastoris. Under conditions of 1% of methanol addition, pH6.0 of medium, 48 h of induction, the maximum expression was obtained. At 4 h reaction, the product of cannabigerol acid (CBGA) was significantly increased, in which attributed to catalysis of substrate CBGA by the recombinant CBDAS. In the following, contents of CBD were significantly increased at 8 h (P

In this study, a novel human-size handheld magnetic particle imaging (MPI) system was developed for the high-precision detection of sentinel lymph nodes for breast cancer. The system consisted of a highly sensitive home-made MPI detection probe, a set of concentric coils pair for spatialization, a solenoid coil for uniform excitation at 8 kHz@1.5 mT, and a full mirrored coil set positioned far away from the scanning area. The mirrored coils formed an extremely effective differential pickup structure which suppressed the system noise as high as 100 dB. The different combination of the inner and outer gradient current made the field free point (FFP) move in the Z direction with a uniform intensity of 0.54T/m, while the scanning in the XY direction was implemented mechanically. The third-harmonic signal of the Superparamagnetic Iron Oxide Nanoparticles (SPIONs) at the FFP was detected and then reconstructed synchronously with the current changes. Experiment results showed that the tomographic detection limit was 30 mm in the Z direction, and the sensitivity was about 10 μg Fe SPIONs at 40 mm distance with a spatial resolution of about 5 mm. In the rat experiment, 54 μg intramuscular injected SPIONs were detected successfully in the sentinel lymph node, in which the tracer content was about 1.2% total injected Fe. Additionally, the effective detection time window was confirmed from 4 to 6 min after injection. Relevant clinical ethics are already in the application process. Large mammalian SLNB MPI experiments and 3D preoperative SLNB imaging will be performed in the future.

Since breast cancer is a heterogeneous disease, there are currently a variety of treatment methods available, including chemotherapy, endocrine therapy, molecular targeted therapy, immunotherapy, radiation therapy, etc. Breast cancer recurrence and metastasis, despite many treatment modalities, constitute a considerable threat to patients’ survival time and pose a clinical challenge that is difficult to tackle precisely. Exosomes have a very special and crucial role in the treatment of drug resistance in breast cancer as a carrier of intercellular communication in the tumor microenvironment. Exosomes and breast cancer treatment resistance have been linked in a growing number of clinical investigations in recent years. This paper covers the status of research on exosomes in the treatment of breast cancer drug resistance and offers theoretical guidance for investigating new strategies to treat breast cancer drug resistance.

Summary: CD9 is a member of the tetraspanin protein family, which has been widely studied in inflammation and cancer, but not in pathological cardiac hypertrophy. In this study, we found that the expression of CD9 was increased in transaortic constriction (TAC) myocardial tissue. Knockdown of CD9 alleviated damage to cardiac function in the TAC model and reduced heart weight, cardiomyocyte size, and degree of fibrosis, and vice versa. Mechanistically, co-immunoprecipitation results showed that CD9 and GP130 can bind to each other in cardiomyocytes, and knockdown of CD9 can reduce the protein level of GP130 and the phosphorylation of STAT3 in vivo and in vitro, and vice versa. GP130 knockdown reversed the aggravating effects of CD9 on pathological cardiac hypertrophy. Therefore, we conclude that CD9 exacerbates pathological cardiac hypertrophy by regulating the GP130/STAT3 signaling pathway and may serve as a therapeutic target for pathological cardiac hypertrophy.

Abstract Background 2-Phenylethanol (2-PE), a higher alcohol with a rose-like odor, inhibits growth of the producer strains. However, the limited knowledge regarding 2-PE tolerance mechanisms renders our current knowledge base insufficient to inform rational design. Results To improve the growth phenotype of Saccharomyces cerevisiae under a high 2-PE concentration, adaptive laboratory evolution (ALE) was used to generate an evolved 19–2 strain. Under 2-PE stress, its OD600 and growth rate increased by 86% and 22% than that of the parental strain, respectively. Through whole genome sequencing and reverse engineering, transcription factor Pdr1p mutation (C862R) was revealed as one of the main causes for increased 2-PE tolerance. Under 2-PE stress condition, Pdr1p mutation increased unsaturated fatty acid/saturated fatty acid ratio by 42%, and decreased cell membrane damage by 81%. Using STRING website, we identified Pdr1p interacted with some proteins, which were associated with intracellular ergosterol content, reactive oxygen species (ROS), and the ATP-binding cassette transporter. Also, the results of transcriptional analysis of genes encoded these proteins confirmed that Pdr1p mutation induced the expression of these genes. Compared with those of the reference strain, the ergosterol content of the PDR1_862 strain increased by 72%–101%, and the intracellular ROS concentration decreased by 38% under 2-PE stress. Furthermore, the Pdr1p mutation also increased the production of 2-PE (11% higher). Conclusions In the present work, we have demonstrated the use of ALE as a powerful tool to improve yeast tolerance to 2-PE. Based on the reverse engineering, transcriptional and physiological analysis, we concluded that Pdr1p mutation significantly enhanced the 2-PE tolerance of yeast by regulating the fatty acid proportion, intracellular ergosterol and ROS. It provides new insights on Pdr1p mediated 2-PE tolerance, which could help in the design of more robust yeasts for natural 2-PE synthesis.

Exosomes derived from human adipose-derived stem cells (hADSCs-Exos) have shown potential as an effective therapeutic tool for repairing bone defects. Although metal-organic framework (MOF) scaffolds are promising strategies for bone tissue regeneration, their potential use for exosome loading remains unexplored. In this study, motivated by the potential advantages of hADSCs-Exos and Mg-GA MOF, we designed and synthesized an exosome-functionalized cell-free PLGA/Mg-GA MOF (PLGA/Exo-Mg-GA MOF) scaffold, taking using of the benefits of hADSCs-Exos, Mg2+, and gallic acid (GA) to construct unique nanostructural interfaces to enhance osteogenic, angiogenic and anti-inflammatory capabilities simultaneously. Our in vitro work demonstrated the beneficial effects of PLGA/Exo-Mg-GA MOF composite scaffolds on the osteogenic effects in human bone marrow-derived mesenchymal stem cells (hBMSCs) and angiogenic effects in human umbilical endothelial cells (HUVECs). Slowly released hADSCs-Exos from composite scaffolds were phagocytosed by co-cultured cells, stabilized the bone graft environment, ensured blood supply, promoted osteogenic differentiation, and accelerated bone reconstruction. Furthermore, our in vivo experiments with rat calvarial defect model showed that PLGA/Exo-Mg-GA MOF scaffolds promoted new bone formation and satisfactory osseointegration. Overall, we provide valuable new insights for designing exosome-coated nanocomposite scaffolds with enhanced osteogenesis property.

Abstract Background High morbidity and mortality of influenza virus infection have made it become one of the most lethal diseases threatening public health; the lack of drugs with strong antiviral activity against virus strains exacerbates the problem. Methods Two independent researchers searched relevant studies using Embase, PubMed, Web of Science, Google Scholar, and MEDLINE databases from its inception to December 2022. Results Based on the different antiviral mechanisms, current antiviral strategies can be mainly classified into virus‐targeting approaches such as neuraminidase inhibitors, matrix protein 2 ion channel inhibitors, polymerase acidic protein inhibitors and other host‐targeting antivirals. However, highly viral gene mutation has underscored the necessity of novel antiviral drug development. Arbidol (ARB) is a Russian‐made indole‐derivative small molecule licensed in Russia and China for the prevention and treatment of influenza and other respiratory viral infections. ARB also has inhibitory effects on many other viruses such as severe acute respiratory syndrome coronavirus 2, Coxsackie virus, respiratory syncytial virus, Hantaan virus, herpes simplex virus, and hepatitis B and C viruses. ARB is a promising drug which can not only exert activity against virus at different steps of virus replication cycle, but also directly target on hosts before infection to prevent virus invasion. Conclusion ARB is a broad‐spectrum antiviral drug that inhibits several viruses in vivo and in vitro, with high safety profile and low resistance; the antiviral mechanisms of ARB deserve to be further explored and more high‐quality clinical studies are required to establish the efficacy and safety of ARB.

Background Lung cancer is one of the most common malignant tumors in the world. It has become an increasingly important public health problem in China. In this study, we systematically assessed the lung cancer situation in China from 1990 to 2019 and provided an epidemiological knowledge base for the revision of health policies. The relevant data were extracted from the Global Burden of Disease (GBD) database. Methods Based on GBD 2019 data, we evaluated the incidence, prevalence, and death rates of lung cancer in China and their change trends from 1990 to 2019, making comparisons by gender and age. Results The age-standardized incidence and death rates (ASIR and ASDR, respectively) of lung cancer in China were higher than the average levels in Asia, Africa, Europe, and Oceania and also higher than those of neighboring Asian countries. Lung cancer rose from the seventh leading cause of death in 1990 to the fourth leading one in 2019, indicating that the disease burden of lung cancer is increasing. In 2019, the incidence, prevalence, and death rates of lung cancer were all higher in men than in women across all age groups. All three indices were lower in men and women 50 years. From 1990 to 2019, the ASIR, age-standardized prevalence rate (ASPR), and ASDR showed trends of increase ( P < .05), and the rise in the ASPR (average annual percentage change [AAPC] = 1.9) was greater than those in the ASIR (AAPC = 1) and ASDR (AAPC = .8). Conclusions From 1990 to 2019, the incidence, prevalence, and death rates of lung cancer continued to increase in China. To reduce this burden, prevention and management of known risk factors should be promoted through national policies.

ABSTRACT This study investigated the resistance mechanisms and the distribution and proportions of virulence genes, including exoU, in 182 imipenem-nonsusceptible Pseudomonas aeruginosa (INS-PA) strains collected from China in 2019. There was no obvious prevalent sequence type or concentrated evolutionary multilocus sequence typing (MLST) type on the INS-PA phylogenetic tree in China. All of the INS-PA isolates harbored β-lactamases with/without other antimicrobial mechanisms, such as gross disruption of oprD and overexpression of efflux genes. Compared with exoU-negative isolates, exoU-positive isolates (25.3%, 46/182) presented higher virulence in A549 cell cytotoxicity assays. The southeast region of China had the highest proportion (52.2%, 24/46) of exoU-positive strains. The most frequent exoU-positive strains belonged to sequence type 463 (ST463) (23.9%, 11/46) and presented multiple resistance mechanisms and higher virulence in the Galleria mellonella infection model. The complex resistance mechanisms in INS-PA and the emergence of ST463 exoU-positive, multidrug-resistant P. aeruginosa strains in southeast China indicated a challenge that might lead to clinical treatment failure and higher mortality. IMPORTANCE This study investigates the resistance mechanisms and distribution and proportions of virulence genes of imipenem-nonsusceptible Pseudomonas aeruginosa (INS-PA) isolates in China in 2019. Harboring PDC and OXA-50-like genes is discovered as the most prevalent resistance mechanism in INS-PA, and the virulence of exoU-positive INS-PA isolates was significantly higher than that of exoU-negative INS-PA isolates. There was an emergence of ST463 exoU-positive INS-PA isolates in Zhejiang, China, most of which presented multidrug resistance and hypervirulence.

Florfenicol (FLO) is a widely used antibacterial drug, which is often detected in the environment. In this paper, the photolysis mechanism of FLO in water was investigated using density functional theory (DFT) and time-dependent density functional theory (TDDFT). The focus of the study is to elucidate the direct photolysis mechanism of FLO in the water environment and the indirect photolysis of free radicals (·OH, ·NO3, and ·SO4−) as active species. The effect of metal ions Ca2+/Mg2+/Zn2+ on the indirect photolysis was also investigated. The results show that the direct photolysis of FLO involves C–C/C–N/C–S bond cleavage, the C5–S7 bond cleavage is most likely to occur, and the C17–C18 cleavage reaction is not easy to occur during the direct photodegradation of FLO. The indirect photolysis of FLO is more likely to occur in the environment than direct photolysis. The main indirect photolysis involves OH-addition, NO3-addition, and SO4-addition on benzene ring. The order of difficulty in the indirect photolysis with ·OH is C2 > C3 > C4 > C5 > C6 > C1, Ca2+ can promote the indirect photolysis with ·OH, and Mg2+/Zn2+ has a dual effect on the indirect photolysis with ·OH. In other words, Mg2+ and Zn2+ can inhibit or promote the indirect photolysis with ·OH. These studies provide important information for theoretical research on the environmental behavior and degradation mechanism of drug molecules.

Cell division in eukaryotes is a highly regulated process that is critical to the life of a cell. Dysregulated cell proliferation, often driven by anomalies in cell Cyclin-dependent kinase (CDK) activation, is a key pathological mechanism in cancer. Recently, selective CDK4/6 inhibitors have shown clinical success, particularly in treating advanced-stage estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This review provides an in-depth analysis of the action mechanism and recent advancements in CDK4/6 inhibitors, categorizing them based on their structural characteristics and origins. Furthermore, it explores proteolysis targeting chimers (PROTACs) targeting CDK4/6. We hope that this review could be of benefit for further research on CDK4/6 inhibitors and PROTACs.

In this work, novel lignin-based nanoparticles (LβNPs) with high acidic tolerance were successfully prepared via electrostatic interaction between β-alanine and lignin nanoparticles. The effects of the mass ratio of lignin nanoparticles to β-alanine and pH value on the morphology and particle sizes of LβNPs were investigated with the aim of obtaining the ideal nanoparticles. The optimized LβNPs were spherical in shape with an average particle size of 41.1 ± 14.5 nm and exhibited outstanding structure stability under high acidic conditions (pH < 4). Subsequently, Pickering emulsions stabilized by LβNPs were prepared using olive oil as the oil phase. Additionally, the effects of pH value, droplet size, morphology, and storage stability on Pickering emulsions were also analyzed. The emulsions displayed excellent stability, and were stable against strongly acidic conditions (pH < 4) after 30 days of storage. The study presented a promising approach to preparing lignin-based nanoparticles with high acidic tolerance (an ideal type of stabilizer to prepare emulsions), and exhibited extremely high potential application values in the fields of drug delivery, food additives, and oily wastewater treatment.

BackgroundIn addition to the COVID-19 waves, the globe is recently facing global monkeypox (MPX) outbreak. As the daily confirmed cases of MPX infection across epidemic and nonepidemic countries are increasing, taking measures to control global pandemic remains crucial. Therefore, this review aimed to provide fundamental knowledge for the prevention and control of future outbreaks of this emerging epidemic.MethodsThe review was conducted using PubMed and Google Scholar databases; the search terms used were "monkeypox," "MPX tropism," "replication signaling of MPX," "biology and pathogenicity of MPX," "diagnosis of MPX," "treatment of MPX," "prevention of MPX," etc. The update epidemic data were collected from the websites of the World Health Organization (WHO), United States Centers for Disease Control and Prevention (CDC), and Africa Center for Disease Control and Prevention (ADCC). High-quality research results published in authoritative journals were summarized and preferred cited. Excluding all duplicates, non-English published references, and irrelevant literature, totally 1,436 articles were assessed for eligibility.ResultsIt is still difficult to diagnose the patient as MPX simply based on clinical manifestations; therefore, under this situation, employing polymerase chain reaction (PCR) technology to provide confirmed evidence for the diagnosis of MPX seems to be the preferred and indispensable strategy. The treatment approach for MPX infection is mainly symptomatic and supportive; anti-smallpox virus drugs including tecovirimat, cidofovir, and brincidofovir can be employed in severe cases. Timely identification and isolation of confirmed cases, cutting off dissemination routes, and vaccination of close contacts are effective measures to control MPX. Also, smallpox vaccines (JYNNEOS, LC16m8, and ACAM2000) can be under consideration due to their immunological cross-protection among Orthopoxvirus. Nevertheless, given the low quality and scarcity of relevant evidence of current antiviral drugs and vaccines, deeply seeking for the MAPK/ERK, PAK-1, PI3K/Akt signaling, and other pathways involved in MPX invasion may provide potential targets for the treatment, prevention, and control of the epidemic.ConclusionsIn response to the current MPX epidemic, the development of vaccines and antiviral drugs against MPX, as well as the rapid and precise diagnostic methods are still urgently needed. Sound monitoring and detection systems should be established to limit the rapid spread of MPX worldwide.

Extracellular vesicles (EVs) are nanoscale extracellular particles that have received widespread scientific attention for carrying a variety of biomolecules such as nucleic acids and proteins and participating in the process of intercellular information exchange, making them become a research hotspot due to their potential diagnostic value. Breast cancer is the leading cause of cancer-related death in women, approximately 90% of patient deaths are due to metastasis complications. Brain metastasis is an important cause of mortality in breast cancer patients, about 10–15% of breast cancer patients will develop brain metastasis. Therefore, early prevention of brain metastasis and the development of new treatments are crucial. Small EVs have been discovered to be involved in the entire process of breast cancer brain metastasis (BCBM), playing an important role in driving organ-specific metastasis, forming pre-metastatic niches, disrupting the blood-brain barrier, and promoting metastatic tumor cell proliferation. We summarize the mechanisms of small EVs in the aforementioned pathological processes at the cellular and molecular levels, and anticipate their potential applications in the treatment of breast cancer brain metastasis, with the hope of providing new ideas for the precise treatment of breast cancer brain metastasis.

Introduction Cancer diagnosis and treatment can impair fertility, and younger female patients with cancer have a particularly strong need for fertility preservation. Fertility preservation decision aids are thought to help patients make proactive and informed treatment decisions. This systematic review aims to assess the effectiveness and feasibility of online fertility preservation decision aids for young female patients with cancer.Methods and analysis PubMed, Web of Science Core Collection, Embase, The Cochrane Central Register of Controlled Trials, PsycINFO and CHINAL, along with three grey literature sources (Google Scholar, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform), will be searched from each database’s establishment to 30 November 2022. Two trained reviewers will independently screen the articles, and the data extraction and methodological quality of eligible randomised controlled trials and quasiexperimental studies will be assessed. A meta-analysis will be performed using Review Manager V.5.4 (Cochrane Collaboration) software, and heterogeneity will be assessed using I² statistics. If a meta-analysis is not possible, a narrative synthesis will be done.Ethics and dissemination Since this systematic review is based on published data, no ethical approval is required. The study’s findings will be disseminated through peer-reviewed publications and conference presentations.PROSPERO registration number CRD42022363287.

Heavy metals have attracted much attention due to their irreversibility, persistence, concealment and bioaccumulation. Biomonitoring method combined chemical analysis can be well evaluate health risks of heavy metals in the environment. In this study, eleven sediments and water samples were collected along Xihe River, which was polluted by heavy metals in Shenyang city of China. The content of multiple heavy metals in these samples was determined by inductively coupled plasma mass spectrometry. 18S rRNA gene sequencing was performed to identify the composition and diversity of nematodes in fine River sediments. The biological toxicity of water-soluble extracts from the samples was further assessed by referring to different endpoints of Caenorhabditis Elegans. The results indicated that the risk of heavy metals in Xihe River was high (potential ecological risk index = 308.75), in which Hg and Cd are the main contributing factors. The relative abundance of nematodes complemented the chemical analysis result, Enoplida, Mononchida, Triplonchida, and Chromadorida nematodes presented a significant positive correlation with the concentration of heavy metals. Specially, Chromadorida nematodes were sensitive to changes in heavy metals in Xihe River, which was significant positively correlated with As, Pb and V. Therefore, nematodes such as Chromadorida can be applied in environmental monitoring to evaluate the health risks of heavy metals.

T cell receptor β-chain constant (TRBC) is a promising class of cancer targets consisting of two highly homologous proteins, TRBC1 and TRBC2. Developing targeted antibody therapeutics against TRBC1 or TRBC2 is expected to eradicate the malignant T cells and preserve half of the normal T cells. Recently, several antibody engineering strategies have been used to modulate the TRBC1 and TRBC2 specificity of antibodies. Here, we used molecular simulation and artificial intelligence methods to quantify the affinity difference in antibodies with various mutations for TRBC1 and TRBC2. The affinity of the existing mutants was verified by FEP calculations aided by the AI. We also performed long-time molecular dynamics simulations to reveal the dynamical antigen recognition mechanisms of the TRBC antibodies.

Bacillus subtilis is a model organism for studying Gram-positive bacteria and serves as a cell factory in the industry for enzyme and chemical production. Additionally, it functions as a probiotic in the gastrointestinal tract, modulating the gut microbiota. Its lytic phage SPO1 is also the most studied phage among the genus Okubovrius, including Bacillus phage SPO1 and Camphawk. One of the notable features of SPO1 is the existence of a “host-takeover module”, a cluster of 24 genes which occupies most of the terminal redundancy. Some of the gene products from the module have been characterized, revealing their ability to disrupt host metabolism by inhibiting DNA replication, RNA transcription, cell division, and glycolysis. However, many of the gene products which share limited similarity to known proteins remain under researched. In this study, we highlight the involvement of Gp49, a gene product from the module, in host RNA binding and heme metabolism—no observation has been reported in other phages. Gp49 folds into a structure that does not resemble any protein in the database and has a new putative RNA binding motif. The transcriptome study reveals that Gp49 primarily upregulates host heme synthesis which captures cytosolic iron to facilitate phage development.

Abstract Background Cerebral small vascular disease (CSVD) is one of the leading causes of death in the aged population and is closely related to abnormalities in low-density lipoprotein cholesterol (LDL-C). Our study aims to clarify the relationship between small and dense low-density lipoprotein cholesterol (sdLDL-C) (a subcomponent of LDL-C) and neuroimaging markers of CSVD. Methods In total, 1211 Chinese adults aged ≥45 years with cranial magnetic resonance imaging (MRI) were recruited in this retrospective study from January 2018 to May 2021. Serum lipids and other baseline characteristics were investigated in relation to the occurrence of CSVD. A logistic regression model was performed to analyze the relationships between LDL subtypes and CSVD risk, and the Pearson correlation coefficient was used to analyze the correlation between clinical characteristics and CSVD risk. ROC curves and AUCs were created and depicted to predict the best cutoff value of LDL-C subtypes for CSVD risk. Based on these data, we performed comprehensive analyses to investigate the risk factors for CSVD. Results Ultimately, 623 eligible patients were included in the present study. Of the 623 eligible patients, 487 were included in the CSVD group, and 136 were included in the group without CSVD (control group). We adjusted for confounders in the multivariate logistic regression model, and LDL-C3 was still higher in the CSVD patients than in the group of those without CSVD (OR (95% CI), 1.22(1.08–1.38), P 0.15, P

ObjectivesTo assess and summarize current evidence on the effectiveness and safety of ertapenem for treatment of childhood infections, in consideration of high infection prevalence in children and wide use of ertapenem.MethodsThe following 8 databases were searched on 13th May 2021: Web of Science, Embase via Ovid SP, PubMed, The Cochrane Library (CENTRAL), Chinese BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), VIP and Wanfang. The primary outcome was treatment success rate. Risk ratios (RRs) and 95% confidence interval (CI) were estimated using random-effect models. Subgroup analysis was conducted where heterogeneity was found.ResultsFifteen studies (8 randomized controlled trials, 1 observational comparative study, and 6 before and after studies) involving 2,528 patients were included in the final review. Ertapenem had similar treatment success rates with β-lactam antibiotics [relative risk (RR) = 1.08, 95% CI: 0.99–1.19]. In a subgroup analysis, similar efficacy (RR = 1.08, 95% CI: 0.97–1.20) between ertapenem and other carbapenems. Compared with β-lactam antibiotics, ertapenem did not increase the risk of any adverse events (RR = 1.02, 95%CI: 0.71–1.48), drug-related diarrhea (all non-Asian children, RR = 0.62, 95%CI: 0.31–1.25), or injection site pain (all non-Asian children, RR = 1.66, 95%CI: 0.59–4.68). Subgroup analysis showed no obvious difference between ertapenem group and carbapenems or non-carbapenems group on risk of adverse events.ConclusionOur findings suggest that ertapenem is effective and safe in treatment for children with infection. Further comparative real-world data is needed to supplement clinical evidence on the overall benefits of ertapenem in this population.

ObjectiveTo determine the prevalence of thyroid nodules in Chinese adult women. To analyze the relationships between lifestyle, metabolic syndrome and thyroid nodules.MethodsWe conducted a retrospective cross-sectional study in the tertiary hospital from 2017 to 2019. Included participants underwent thyroid color Doppler ultrasonography, lipids examination, and dietary evaluation.ResultsTotally 2,784 participants were included, and 933 participants were found to have thyroid nodule(s) by B-ultrasound. The prevalence of thyroid nodules was 33.3%. Women in 50-59 years (OR: 1.746, 95% CI [1.356-2.249]), older than 60 (2.147 [1.540-2.993]) and occupations with mainly manual work (1.780 [1.367-2.317]) were risk factors for thyroid nodules, while moderate dietary diversity (0.624 [0.476-0.817]) and normal triglycerides level (0.739 [0.604-0.905]) were protective factors.ConclusionWomen over 50 and those whose jobs are mainly manual should enhance screening, follow-up and health management of thyroid nodules. Higher dietary diversity is protective measures against thyroid nodules for adult women and should consider dietary balance and the food varieties, not just increased quantities.

(1) Background: Green and open spaces are conducive to physical activity for the elderly. However, it is unclear how different landscape characteristics relate to the physical activity of the elderly. (2) Methods: following the PRISMA method, this study reviewed the existing literature on the landscape characteristics correlated with the elderly’s physical activity (PA) from Web of Science, Scopus, and PubMed. We conducted a systematic full-text review of 25 eligible reports and studies related to the linkage between the characteristics of green and open spaces and the elderly’s physical activity (PA); (3) Results: Nature/greenery, safety, road/path conditions, aesthetics, PA facilities, accessibility, amenity, water, and elderly accessibility facilities were found to be positively associated with elderly’s PA. Pavement conditions (gravel), the presence of water, poor maintenance, neighborhood aesthetics, and GVI are negatively correlated with the elderly’s PA; (4) Conclusions: We close the paper by making a few recommendations for future policy-making, practice, and research. It is suggested that the landscape characteristics be applied in evidence-based policy-making and design, and in tackling health inequality. Future research should be more specific about the impact of site-scale factors, include landscape characteristics specifically needed by the elderly to conduct PA, and involve a wider scope of green and open space on top of neighborhood green and open space and parks. Additionally, these studies should take into consideration different cultural settings and geographical scales to reveal the different effects of various aspects of green and open space.

Human brain-related disorders, such as autism spectrum disorder (ASD), are often characterized by cell heterogeneity, as the cell atlas of brains consists of diverse cell types. There are commonality and specificity in gene expression among different cell types of brains; hence, there may also be commonality and specificity in dysregulated gene expression affected by ASD among brain cells. Moreover, as genes interact together, it is important to identify shared and cell-type-specific ASD-related gene modules for studying the cell heterogeneity of ASD. To this end, we propose integrative regularized non-negative matrix factorization (iRNMF) by imposing a new regularization based on integrative non-negative matrix factorization. Using iRNMF, we analyze gene expression data of multiple cell types of the human brain to obtain shared and cell-type-specific gene modules. Based on ASD risk genes, we identify shared and cell-type-specific ASD-associated gene modules. By analyzing these gene modules, we study the commonality and specificity among different cell types in dysregulated gene expression affected by ASD. The shared ASD-associated gene modules are mostly relevant to the functioning of synapses, while in different cell types, different kinds of gene functions may be specifically dysregulated in ASD, such as inhibitory extracellular ligand-gated ion channel activity in GABAergic interneurons and excitatory postsynaptic potential and ionotropic glutamate receptor signaling pathway in glutamatergic neurons. Our results provide new insights into the molecular mechanism and pathogenesis of ASD. The identification of shared and cell-type-specific ASD-related gene modules can facilitate the development of more targeted biomarkers and treatments for ASD.

BCL9 is an activator of oncogenic Wnt/β-catenin. Here, the authors show a β-catenin independent function of BCL9 in a subtype of colorectal cancers, where it interacts with paraspeckle proteins to enhance the mRNA stability of calcium signalling and neural associated genes to promote communication with tumour cells and its microenvironment.