Clinical Diagnostic Challenge in a Case of Disseminated Talaromyces marneffei Infection Misdiagnosed Initially as Pulmonary Tuberculosis: A Case Report and Literature Review.

This case reports a middle-aged male patient who was HIV-negative and initially misdiagnosed as pulmonary tuberculosis but was eventually diagnosed with disseminated Talaromyces marneffei (T. marneffei) infection by next-generation sequencing. The patient presented with respiratory symptoms, recurrent bone pain, and subcutaneous masses as the main symptoms. After one year of antifungal treatment, the symptoms improved obviously, but the symptoms recurred after two weeks of drug withdrawal, and the symptoms were relieved after re-administration of antifungal drugs again. This report highlights the need for the rapid evaluation of fungal infections with metagenomic next-generation sequencing (mNGS) in patients with an inadequate diagnostic basis for tuberculosis infection or a poor response to antituberculosis drugs. In addition, long-term follow-up is needed to observe disease recurrence in patients with disseminated T. marneffei infection.

Effects of climate change and deep fertilization on the growth and yield of winter wheat in the Loess Plateau of China.

BACKGROUND: Global temperature is projected to rise continuously under climate change, negatively impacting the growth and yield of winter wheat. Optimizing traditional agricultural measures is necessary to mitigate potential winter wheat yield losses caused by future climate change. This study aims to explore the variations in winter wheat growth and yield on the Loess Plateau of China under future climate change, identify the key meteorological factors affecting winter wheat growth and yield, and analyze the differences in winter wheat yield and root characteristics under different fertilization depths. RESULTS: Meteorological data from 20 General Circulation Models were applied to drive the Decision Support System for Agrotechnology Transfer model, simulating the future growth characteristics of winter wheat under various fertilization depths. The Random Forest model was used to determine the relative importance of meteorological factors influencing winter wheat yield, root length density and leaf area index. The results showed that temperature and high emission concentration were primary factors influencing crop yield under future climate change. The temperature increase projected from 2021 to 2100 would be anticipated to shorten the phenology period of winter wheat by 2-16 days and reduce grain yield by 2.9-12.7% compared to the period from 1981 to 2020. Conversely, the root length density and root weight of winter wheat would increase by 1.2-10.9% and 0.2-24.1%, respectively, in the future, and excessive allocation of root system resources was identified as a key factor contributing to the reduction in winter wheat yield. Compared with the shallow fertilization treatment (N5), the deep fertilization treatments (N15 and N25) increased the proportion of roots in the deep soil layer (30-60 cm) by 2.7-10.2%. Because of the improvement in root structure, the decline in winter wheat yield under deep fertilization treatments in the future is expected to be reduced by 1.2% to 6.5%, whereas water use efficiency increases by 1.1% to 2.4% compared to the shallow fertilization treatment. CONCLUSION: The deep fertilization treatment can enhance the root structure of winter wheat and increase the proportion of roots in the deep soil layer, thereby effectively mitigating the decline in winter wheat yield under future climate change. Overall, optimizing fertilization depth effectively addresses the reduced winter wheat yield risks and agricultural production challenges under future climate change. © 2024 Society of Chemical Industry.

Association of seminal plasma zinc levels with human semen quality and its toxic effects on sperm motility.

Infertility has become one of the most common chronic diseases among reproductive- aged individuals, and male factors account for about 50 %. Zinc is a trace element that is essential for sperm quality and male reproductive system. Although several current studies with small sample sizes have investigated this relationship, the conclusions have been still controversial. Here, using a large population sample involved 25,915 participants from Changzhou Maternity and Child Health Care Hospital, we revealed an inverted "U"-shaped trend between seminal plasma zinc concentrations and sperm motility PR/PR + NP (PR, progressive motility; NP, non-progressive motility). The results showed that the highest values of sperm PR/PR + NP observed in the group with intermediate concentrations of zinc (Group 2, 0.25-2.11 mmol/L). The mean values were 43.17 ± 19.03 % and 56.64 ± 20.28 %, respectively. And the lowest values came out in the highest zinc levels group (Group 4, > 3.04 mmol/L). In vitro cell experiments also showed that zinc caused dose-dependent cytotoxicity for GC-2 cells at a threshold value. Furthermore, RNA-seq analysis demonstrated that high concentrations of zinc exerted toxic effects on GC-2 cells through immune injury. Taken together, our findings suggested that moderate amounts of zinc are crucial for human reproduction and excessive concentrations may have adverse effects on male fertility.

Autologous exosomes loaded with a rationally designed photosensitizer for enhanced photodynamic therapy.

We present generalizing statistical surrogate models to select an optimized photosensitizer, TPP, which is subsequently loaded into autologous exosomes by ultrasonic mixing to achieve tumor targeting with enhanced therapeutic efficacy by photodynamic therapy (PDT). This work contributes to the exploration of PDT enhancement strategies, and provides new prospects for using autologous exosomes as a delivery system.

[Progress and perspectives of natural cell factories for chemical production from methanol].

Methanol has been considered one of the most important alternative carbon sources for the next-generation biomanufacturing due to its low price, mature production processes, and potential sustainability. Constructing microbial cell factories for methanol to chemical biotransformation has become a research hotspot in the green biomanufacturing industry. Focusing on the microorganisms that can naturally use methanol, we compare them with non-natural cell factories for chemical production from methanol. We discuss the key issues and challenges associated with natural cell factories for chemical production from methanol, summarize recent research progress surrounding these issues, and propose possible solutions to these challenges. This review helps to generate feasible guidelines and research strategies for the modification of natural cell factories for efficient methanol to chemical production in the future.

Pim-1 kinase protects the liver from ischemia reperfusion injury by regulating dynamics-related protein 1.

Hepatic ischemia-reperfusion (IR) injury significantly impacts liver transplantation success, yet current treatments remain inadequate. This study explores the role of Proto-oncogene serine/threonine-protein kinase (Pim-1) in liver IR, an area previously unexplored. Utilizing a mouse liver IR in vivo model and a MIHA cell hypoxia-reoxygenation in vitro model, we observed that Pim-1 expression increases following IR, inversely correlating with serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Increased Pim-1 expression stabilizes mitochondrial membranes by modifying Drp1 phosphorylation, reducing mitochondrial fission and apoptosis, thereby mitigating liver damage. Additionally, we discovered that elevated Pim-1 expression is dependent on the trimethylation of histone H3 lysine 9 during liver IR. These findings underscore the importance and potential clinical application of targeting Pim-1 in treating hepatic IR, presenting a novel therapeutic avenue.

Self-Sensing Electromechanical System Integrated with the Embedded Displacement Sensor.

Conventionally, the electromechanical system requires the installation of auxiliary displacement sensors and only the amount on the drive part and motion end, which increases volume, cost, and measurement error in the system. This paper presents an integrated measurement method with a sensing head, which takes the equal division characteristics of mechanical structures as part of the sensor, thus, the so-called self-sensing system. Moreover, the displacement is measured by counting the time pulses. The sensing head is integrated with the entire electromechanical system, including the driving, transmitting, and moving parts. Thus, the integration of the sensing part is greatly improved. Taking the rotary table as a special example, and the sensing head embedded into each part of the system, displacement information is obtained by the common processing system and fused by the adaptive weighted average method. The results of the experiment show that the fusion precision of each component is higher than only the motor position information as the feedback. The proposed method is a practical self-sensing technology with significant volume reduction and intelligent control benefits in the industry, especially suitable for extremely small and narrow spaces.

Demethylase FTO-mediated m6A modification of SIK1 modulates placental cytotrophoblast syncytialization in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) represents a common complication during pregnancy that affects fetoplacental development. We demonstrated the existence of impaired trophoblast syncytialization under hyperglycemic conditions. However, the exact mechanism remains unknown. RNA N6-methyladenosine (m6A) is an emerging regulatory mechanism of mRNA and participates in various biological processes. We described the global m6A modification pattern in T2DM placenta by the combined analysis of methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and RNA sequencing (RNA-Seq). Both the m6A modification and expression of SIK1, which is critical for syncytialization, were significantly decreased in trophoblast exposed to hyperglycemic conditions. In addition, the m6A demethylase fat mass and obesity-associated protein (FTO) affects the expression and mRNA stability of SIK1 by binding to its 3'-untranslated region (UTR) m6A site. This work reveals that the FTO-m6A-SIK1 axis plays critical roles in regulating syncytialization in the placenta.

Visible-Light Self-Powered Photodetector with High Sensitivity Based on the Type-II Heterostructure of CdPSe3/MoS2.

Transition metal thiophosphates (MTPs) are a group of emerging van der Waals materials with widely tunable band gaps. In the MTP family, CdPSe3 is demonstrated to possess a wide energy band gap and high carrier mobility, making it a potential candidate in optoelectronic applications. Here, we reported photoelectric response behaviors of both CdPSe3- and CdPSe3/MoS2-based photodetectors (noted as CPS and CM, respectively); these showed prominent photoelectric performances, and the latter proved to be significantly superior to the former. These devices exhibited ultralow dark current at a magnitude order of 10-12 A and fine cycle and air stabilities. Compared with CPS, CM demonstrated the highest responsivity (91.12 mA/W) and detectivity (1.74 × 1011 Jones) at 5 V under 425 nm light illumination. Besides, CM showed self-powered photoelectric responses at zero bias, which was attributed to the improved separation efficiency of photogenerated carriers by the built-in electric field at the interface of the p-n junction. This work proves a prospect for the CM device in portable, self-powered optoelectronic device applications.

Characterization and efficacy against carbapenem-resistant Acinetobacter baumannii of a novel Friunavirus phage from sewage.

Carbapenem-resistant Acinetobacter baumannii (CRAB) has become a new threat in recent years, owing to its rapidly increasing resistance to antibiotics and new effective therapies are needed to combat this pathogen. Phage therapy is considered to be the most promising alternative for treating CRAB infections. In this study, a novel phage, Ab_WF01, which can lyse clinical CRAB, was isolated and characterized from hospital sewage. The multiplicity of infection, morphology, one-step growth curve, stability, sensitivity, and lytic activity of the phage were also investigated. The genome of phage Ab_WF01 was 41, 317 bp in size with a GC content of 39.12% and encoded 51 open reading frames (ORFs). tRNA, virulence, and antibiotic resistance genes were not detected in the phage genome. Comparative genomic and phylogenetic analyses suggest that phage Ab_WF01 is a novel species of the genus Friunavirus, subfamily Beijerinckvirinae, and family Autographiviridae. The in vivo results showed that phage Ab_WF01 significantly increased the survival rate of CRAB-infected Galleria mellonella (from 0% to 70% at 48 h) and mice (from 0% to 60% for 7 days). Moreover, after day 3 post-infection, phage Ab_WF01 reduced inflammatory response, with strongly ameliorated histological damage and bacterial clearance in infected tissue organs (lungs, liver, and spleen) in mouse CRAB infection model. Taken together, these results show that phage Ab_WF01 holds great promise as a potential alternative agent with excellent stability for against CRAB infections.

Emerging roles of FOXK2 in cancers and metabolic disorders.

FOXK2, a member of the Forkhead box K (FOXK) transcription factor family, is widely expressed in various tissues and organs throughout the body. FOXK2 plays crucial roles in cell proliferation, differentiation, autophagy, de novo nucleotide biosynthesis, DNA damage response, and aerobic glycolysis. Although FOXK2 is recognized as an oncogene in colorectal cancer and hepatocellular carcinoma, it acts as a tumor suppressor in breast cancer, cervical cancer, and non-small cell lung cancer (NSCLC). This review provides an overview of the recent progress in understanding the regulatory mechanisms of FOXK2 and its downstream targets, highlights the significant impact of FOXK2 dysregulation on cancer etiology, and discusses the potential of targeting FOXK2 for cancer treatment.

Ovarian Hyperstimulation syndrome combined with hypothyroidism: a comprehensive review.

Ovarian Hyperstimulation Syndrome (OHSS) is a systemic condition marked by the enlargement of the ovaries and heightened vascular permeability. And hypothyroidism (HT) emerges as a potential risk factor for OHSS occurrence. This review presented a comprehensive summary of pertinent case reports involving patients diagnosed with both HT and OHSS. Detailed exploration was conducted into their clinical presentations, diagnostic methodologies, and treatment modalities. Additionally, the review delved into potential interaction mechanisms between HT and OHSS, encompassing various aspects including hormone levels. Moreover, management strategies for mitigating the risk of OHSS in HT patients were thoroughly reviewed and the importance of monitoring thyroid function in those experiencing OHSS was emphasized. This review indicated that the association between HT and OHSS, underscoring its multifaceted complexity. It could accentuate the ongoing necessity for rigorous research and clinical refinement to deepen our comprehension of this association and to bolster diagnostic and therapeutic methodologies for optimal patient care. In conclusion, this review offered valuable insights for future research directions and clinical practices for patients afflicted with OHSS and HT.

Interactions between host and gut microbiota in gestational diabetes mellitus and their impacts on offspring.

Gestational diabetes mellitus (GDM) is characterized by insulin resistance and low-grade inflammation, and most studies have demonstrated gut dysbiosis in GDM pregnancies. Overall, they were manifested as a reduction in microbiome diversity and richness, depleted short chain fatty acid (SCFA)-producing genera and a dominant of Gram-negative pathogens releasing lipopolysaccharide (LPS). The SCFAs functioned as energy substance or signaling molecules to interact with host locally and beyond the gut. LPS contributed to pathophysiology of diseases through activating Toll-like receptor 4 (TLR4) and involved in inflammatory responses. The gut microbiome dysbiosis was not only closely related with GDM, it was also vital to fetal health through vertical transmission. In this review, we summarized gut microbiota signature in GDM pregnancies of each trimester, and presented a brief introduction of microbiome derived SCFAs. We then discussed mechanisms of microbiome-host interactions in the physiopathology of GDM and associated metabolic disorders. Finally, we compared offspring microbiota composition from GDM with that from normal pregnancies, and described the possible mechanism.

Hydroxytyrosol acetate from olive leaves (Olea Europaea L.) induces apoptosis via mitochondrial pathway in BEL7402 cell line.

Hydroxytyrosol acetate is one of the polyphenolic compounds in olive leaves. Hydroxytyrosol acetate has a variety of biological activities, such as antibacterial, antioxidant, anti-inflammatory, cognitive improvement and neuroprotective effects. However, there is no report on the antitumor activity and the antitumor mechanism of hydroxytyrosol acetate. In our study, we studied the antitumor activity of hydroxytyrosol acetate by MTT assay and determined the antitumor mechanism by DNA ladder assay, mitochondrial membrane potential assay and western blot assay. We found that hydroxytyrosol acetate could inhibit cell proliferation, and the inhibition rate was 78.08%. The further researches showed that hydroxytyrosol acetate could downregulate Bcl-2 protein while upregulate Bax protein. It also could induce mitochondrial depolarisation and release of cytochrome C. These results indicated that hydroxytyrosol acetate might induce BEL7402 cells apoptosis via mitochondrial pathway.

Deacylases-structure, function, and relationship to diseases.

Reversible S-acylation plays a pivotal role in various biological processes, modulating protein functions such as subcellular localization, protein stability/activity, and protein-protein interactions. These modifications are mediated by acyltransferases and deacylases, among which the most abundant modification is S-palmitoylation. Growing evidence has shown that this rivalrous pair of modifications, occurring in a reversible cycle, is essential for various biological functions. Aberrations in this process have been associated with various diseases, including cancer, neurological disorders, and immune diseases. This underscores the importance of studying enzymes involved in acylation and deacylation to gain further insights into disease pathogenesis and provide novel strategies for disease treatment. In this Review, we summarize our current understanding of the structure and physiological function of deacylases, highlighting their pivotal roles in pathology. Our aim is to provide insights for further clinical applications.

Carbon Dots Derived from Curcumae Radix and Their Heartprotective Effect.

Background: Acute myocardial infarction (AMI) is a common cardiovascular disease in clinic. Currently, there is no specific treatment for AMI. Carbon dots (CDs) have been reported to show excellent biological activities, which hold promise for the development of novel nanomedicines for the treatment of cardiovascular diseases. Methods: In this study, we firstly prepared CDs from the natural herb Curcumae Radix Carbonisata (CRC-CDs) by a green, simple calcination method. The aim of this study is to investigate the cardioprotective effect and mechanism of CRC-CDs on isoproterenol (ISO) -induced myocardial infarction (MI) in rats. Results: The results showed that pretreatment with CRC-CDs significantly reduced serum levels of cardiac enzymes (CK-MB, LDH, AST) and lipids (TC, TG, LDL) and reduced st-segment elevation and myocardial infarct size on the ECG in AMI rats. Importantly, cardiac ejection fraction (EF) and shortening fraction (FS) were markedly elevated, as was ATPase activity. In addition, CRC-CDs could significantly increase the levels of superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and reduce the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in myocardial tissue, thereby exerting cardioprotective effect by enhancing the antioxidant capacity of myocardial tissue. Moreover, the TUNEL staining image showed that positive apoptotic cells were markedly declined after CRC-CDs treatment, which indicate that CRC-CDs could inhibit cardiomyocyte apoptosis. Importantly, The protective effect of CRC-CDs on H2O2 -pretreated H9c2 cells was also verified in vitro. Conclusion: Taken together, CRC-CDs has the potential for clinical application as an anti-myocardial ischemia drug candidate, which not only provides evidence for further broadening the biological application of cardiovascular diseases, but also offers potential hope for the application of nanomedicine to treat intractable diseases.

Research Progress on the Correlation between Acetaldehyde Dehydrogenase 2 and Hepatocellular Carcinoma Development.

Hepatocellular carcinoma (HCC) is the predominant pathologic type of primary liver cancer. It is a malignant tumor of liver epithelial cells. There are many ways to treat HCC, but the survival rate for HCC patients remains low. Therefore, understanding the underlying mechanisms by which HCC occurs and develops is critical to explore new therapeutic targets. Aldehyde dehydrogenase 2 (ALDH2) is an important player in the redox reaction of ethanol with endogenous aldehyde products released by lipid peroxidation. Increasing evidence suggests that ALDH2 is a crucial regulator of human tumor development, including HCC. Therefore, clarifying the relationship between ALDH2 and HCC is helpful for formulating rational treatment strategies. This review highlights the regulatory roles of ALDH2 in the development of HCC, elucidates the multiple potential mechanisms by which ALDH2 regulates the development of HCC, and summarizes the progress of research on ALDH2 gene polymorphisms and HCC susceptibility. Meanwhile, we envision viable strategies for targeting ALDH2 in the treatment of HCC SIGNIFICANCE STATEMENT: Numerous studies have aimed to explore novel therapeutic targets for HCC, and ALDH2 has been reported to be a critical regulator of HCC progression. This review discusses the functions, molecular mechanisms, and clinical significance of ALDH2 in the development of HCC and examines the prospects of ALDH2-based therapy for HCC.

Simultaneous Pore Detection and Morphological Features Extraction in Laser Powder Bed Fusion with Image Processing.

Internal pore defects are inevitable during laser powder bed fusion (LPBF), which have a significant impact on the mechanical properties of the parts. Therefore, detecting pores and obtaining their morphology will contribute to the quality of LPBF parts. Currently, supervised models are used for defect image detection, which requires a large amount of LPBF sample data, image labeling, and computing power equipment during the training process, resulting in high detection costs. This study extensively collected LPBF sample data and proposed a method for pore defect classification by obtaining its morphological features while detecting pore defects in optical microscopy (OM) images under various conditions. Compared with other advanced models, the proposed method achieves better detection accuracy on pore defect datasets with limited data. In addition, quickly detecting pore defects in a large number of labeling ground truth images will also contribute to the development of deep learning. In terms of image segmentation, the average accuracy scores of this method in the test images exceed 85%. The research results indicate that the algorithm proposed in this paper is suitable for quickly and accurately identifying pore defects from optical microscopy images.

The role of transcriptional regulators in metal ion homeostasis of Mycobacterium tuberculosis.

Metal ions are essential trace elements for all living organisms and play critical catalytic, structural, and allosteric roles in many enzymes and transcription factors. Mycobacterium tuberculosis (MTB), as an intracellular pathogen, is usually found in host macrophages, where the bacterium can survive and replicate. One of the reasons why Tuberculosis (TB) is so difficult to eradicate is the continuous adaptation of its pathogen. It is capable of adapting to a wide range of harsh environmental stresses, including metal ion toxicity in the host macrophages. Altering the concentration of metal ions is the common host strategy to limit MTB replication and persistence. This review mainly focuses on transcriptional regulatory proteins in MTB that are involved in the regulation of metal ions such as iron, copper and zinc. The aim is to offer novel insights and strategies for screening targets for TB treatment, as well as for the development and design of new therapeutic interventions.

The role of perioperative sedative anesthetics in preventing postoperative delirium: a systematic review and network-meta analysis including 6679 patients.

OBJECTIVE: Postoperative delirium is a common and debilitating complication that significantly affects patients and their families. The purpose of this study is to investigate whether there is an effective sedative that can prevent postoperative delirium while also examining the safety of using sedatives during the perioperative period. METHODS: The net-meta analysis was used to compare the incidence of postoperative delirium among four sedatives: sevoflurane, propofol, dexmedetomidine, and midazolam. Interventions were ranked according to their surface under the cumulative ranking curve (SUCRA). RESULTS: A total of 41 RCT studies involving 6679 patients were analyzed. Dexmedetomidine can effectively reduce the incidence of postoperative delirium than propofol (OR 0.47 95% CI 0.25-0.90), midazolam (OR 0.42 95% CI 0.17-1.00), normal saline (OR 0.42 95% CI 0.33-0.54) and sevoflurane (OR 0.39 95% CI 0.18-0.82). The saline group showed a significantly lower incidence of bradycardia compared to the group receiving dexmedetomidine (OR 0.55 95% CI 0.37-0.80). In cardiac surgery, midazolam (OR 3.34 95%CI 2.04-5.48) and normal saline (OR 2.27 95%CI 1.17-4.39) had a higher rate of postoperative delirium than dexmedetomidine, while in non-cardiac surgery, normal saline (OR 1.98 95%CI 1.44-2.71) was more susceptible to postoperative delirium than dexmedetomidine. CONCLUSION: Our analysis suggests that dexmedetomidine is an effective sedative in preventing postoperative delirium whether in cardiac surgery or non-cardiac surgery. The preventive effect of dexmedetomidine on postoperative delirium becomes more apparent with longer surgical and extubation times. However, it should be administered with caution as it was found to be associated with bradycardia.