Association between atherogenic index of plasma and depressive symptoms in US adults: Results from the National Health and Nutrition Examination Survey 2005 to 2018.

OBJECTIVE: This study, utilizing data from the U.S. National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018, investigates the association between the atherogenic index of plasma (AIP), a lipid biomarker, and symptoms of depression in American adults. METHODS: In this cross-sectional study of 12,534 adults aged 20 years and older, depressive symptoms were measured utilizing the Patient Health Questionnaire-9 (PHQ-9) scale. Weighted logistic regression models were employed to scrutinize the independent relationship between AIP levels and the likelihood of developing such symptoms. Moreover, a series of subgroup analyses were conducted to delve deeper into these relationships. RESULTS: Following adjustment for confounders, logistic regression by grouping AIP into quartiles revealed a significant association between AIP and an augmented likelihood of self-reported depression. Participants in the fourth quartile (Q4) exhibited a higher odds ratio (OR = 1.34, 95 % CI: 1.02-1.75, p < 0.05) compared to those in the first quartile (Q1). Notably, subgroup analysis unveiled significant interactions involving the smoking and diabetes subgroups, indicating that smoking status and diabetes may modify the relationship between AIP and depression incidence. CONCLUSION: This study reveals a positive correlation between AIP and the self-reported likelihood of depression among US adults, thereby underscoring AIP's potential clinical utility as a biomarker for depressive disorders. Our findings emphasize the necessity to consider and optimize cardiovascular health factors within depression management strategies and offer fresh insights into the development of risk stratification and intervention methods for psychiatric conditions.

Epidemiological investigation of Entamoeba in wild rhesus macaques in China: A novel ribosomal lineage and genetic differentiation of Entamoeba nuttalli.

Wild rhesus macaques are a potential source of zoonotic parasites for humans, and Entamoeba spp. are common intestinal parasites. To investigate the prevalence of Entamoeba in wild rhesus macaques in China and explore the genetic differentiation of the potentially pathogenic species Entamoeba nuttalli, a total of 276 fecal samples from five populations at high altitudes (HAG, 2,800-4,100 m above sea level) and four populations at low altitudes (LAG, 5-1,000 m above sea level) were collected. PCR methods based on the ssrRNA gene were used to detect Entamoeba infection. Genotyping of E. nuttalli was performed based on six tRNA-linked short tandem repeat (STR) loci for further genetic analyses. The results revealed that Entamoeba infection (69.2%) was common in wild rhesus macaques in China, especially in LAG which had a significantly higher prevalence rate than that in HAG (P < 0.001). Three zoonotic species were identified: Entamoeba chattoni (60.9%) was the most prevalent species and distributed in all the populations, followed by Entamoeba coli (33.3%) and Entamoeba nuttalli (17.4%). In addition, a novel Entamoeba ribosomal lineage named RL13 (22.8%) was identified, and phylogenetic analysis revealed a close genetic relationship between RL13 and Entamoeba. hartmanni. Genotyping of E. nuttalli obtained 24 genotypes from five populations and further analysis showed E. nuttalli had a high degree of genetic differentiation (FST > 0.25, Nm < 1) between the host populations. The result of analysis of molecular variance (AMOVA) revealed that observed genetic differences mainly originate from differences among populations (FST = 0.91). Meanwhile, the phylogenetic tree showed that these genotypes of E. nuttalli were clustered according to geographical populations, indicating a significant phylogeographic distribution pattern. Considering the potential pathogenicity of E. nuttalli, attention should be paid to its risk of zoonotic transmission.

Cmtm4 deficiency exacerbates colitis by inducing gut dysbiosis and S100A8/9 expression.

The dysfunction of innate immunity components is one of the major drivers for ulcerative colitis (UC), and increasing reports indicate that gut microbiome serves as an intermediate between genetic mutations and UC development. Here, we find that the IL-17 receptor subunit, CMTM4, is reduced in UC patients and DSS-induced colitis. The deletion of CMTM4 (Cmtm4-/-) in mice leads to a higher susceptibility to DSS-induced colitis in comparison to wildtype, and the gut microbiome significantly changes in the composition. The causal role of gut microbiome is confirmed with co-housing experiment. We further identify that S100a8/9 is significantly up-regulated in Cmtm4-/- colitis, with the block of its receptor RAGE that reverses the phenotype associated with the CMTM4 deficiency. CMTM4 deficiency rather suppresses S100a8/9 expression in vitro via the IL17 pathway, further supporting that the elevation of S100a8/9 in vivo is most likely a result of microbial dysbiosis. Taken together, the results suggest that CMTM4 is involved in the maintenance of the intestinal homeostasis, suppression of S100a8/9, and prevention of the colitis development. Our study further shows CMTM4 as a crucial innate immunity component, confirming its important role in the UC development and providing insights into potential targets for development of future therapies.

Bioluminescence Imaging of Potassium Ion Using a Sensory Luciferin and an Engineered Luciferase.

Bioluminescent indicators are power tools for studying dynamic biological processes. In this study, we present the generation of novel bioluminescent indicators by modifying the luciferin molecule with an analyte-binding moiety. Specifically, we have successfully developed the first bioluminescent indicator for potassium ions (K+), which are critical electrolytes in biological systems. Our approach involved the design and synthesis of a K+-binding luciferin named potassiorin. Additionally, we engineered a luciferase enzyme called BRIPO (bioluminescent red indicator for potassium) to work synergistically with potassiorin, resulting in optimized K+-dependent bioluminescence responses. Through extensive validation in cell lines, primary neurons, and live mice, we demonstrated the efficacy of this new tool for detecting K+. Our research demonstrates an innovative concept of incorporating sensory moieties into luciferins to modulate luciferase activity. This approach has great potential for developing a wide range of bioluminescent indicators, advancing bioluminescence imaging (BLI), and enabling the study of various analytes in biological systems.

Target proteins-regulated DNA nanomachine-electroactive substance complexes enable separation-free electrochemical detection of clinical exosome.

Simple and reliable profiling of tumor-derived exosomes (TDEs) holds significant promise for the early detection of cancer. Nonetheless, this remains challenging owing to the substantial heterogeneity and low concentration of TDEs. Herein, we devised an accurate and highly sensitive electrochemical sensing strategy for TDEs via simultaneously targeting exosomal mucin 1 (MUC1) and programmed cell death ligand 1 (PD-L1). This approach employs high-affinity aptamers as specific recognition elements, utilizes rolling circle amplification and DNA nanospheres as effective bridges and signal amplifiers, and leverages methylene blue (MB) and doxorubicin (DOX) as robust signal reporters. The crux of this separation- and label-free method is the specific response of MB and DOX to G-quadruplex structures and DNA nanospheres, respectively. Quantifying TDEs using this strategy enabled precise discrimination of lung cancer patients (n = 25) from healthy donors (n = 12), showing 100% specificity (12/12), 92% sensitivity (23/25), and an overall accuracy of 94.6% (35/37), with an area under the receiver operating characteristic curve (AUC) of 0.97. Furthermore, the assay results strongly correlated with findings from computerized tomography and pathological analyses. Our approach could facilitate the early diagnosis of lung cancer through TDEs-based liquid biopsy.

Functional roles of circular RNAs in lung injury.

Lung injury leads to respiratory dysfunction, low quality of life, and even life-threatening conditions. Circular RNAs (circRNAs) are endogenous RNAs produced by selective RNA splicing. Studies have reported their involvement in the progression of lung injury. Understanding the roles of circRNAs in lung injury may aid in elucidating the underlying mechanisms and provide new therapeutic targets. Thus, in this review, we aimed to summarize and discuss the characteristics and biological functions of circRNAs, and their roles in lung injury from existing research, to provide a theoretical basis for the use of circRNAs as a diagnostic and therapeutic target for lung injury.

Chinese herbal medicines for the treatment of depression: a systematic review and network meta-analysis.

Objectives: Amidst rising global burden of depression and the associated challenges with conventional antidepressant therapies, there is a growing interest in exploring the efficacy and safety of alternative treatments. This study uses a Bayesian network meta-analysis to rigorously evaluate the therapeutic potential of Chinese herbal medicines in the treatment of depression, focusing on their comparative efficacy and safety against standard pharmacological interventions. Methods: Five databases (PubMed, Wanfang Data, EMBASE, CNKI, and the Cochrane Library) and grey literature were searched from inception to end of July 2023 to identify studies that assessed the efficacy and safety of Chinese herbal medicines in treating depression. The response rate, Hamilton Depression Scale (HAMD) scores, and rates of adverse events were assessed through both direct and indirect comparisons. Data extraction and risk of bias assessment were meticulously performed. Statistical analysis used Markov chain Monte Carlo methods, with effect size estimates provided as odd ratios and their 95% confidence intervals. Results: A total of 198 RCTs involving 8,923 patients were analyzed, assessing 17 Chinese herbal medicines. Surface Under the Cumulative Ranking results indicated that the top three treatments with the best response rate were possibly Guipiwan, Ease Pill, and Chaihu Jia Longgu Muli Decoction; the top three treatments on the reduction of HAMD scores were Chai Hu Shu Gan San, Xingnao Jieyu Decoction, and Xiaoyao Powder; and the top three treatments with the lowest adverse effects rates were Xiaoyao Powder, Alprazolam, and Xingnao Jieyu Decoction. Interestingly, commonly used synthetic drugs such as Fluoxetine, Escitalopram, Amitriptyline, Sertraline, Flupentixol and Melitracen, and Venlafaxine, not only appeared to be less effective than specific Chinese herbal medicines (Gan Mai Da Zao Decoction, Chaihu Jia Longgu Muli Decoction, Chai Hu Shu Gan San, Danzhi-Xiaoyao-San, and Xingnao Jieyu Decoction), but they were also related to substantially higher risk of adverse events. Conclusion: Our findings elucidate the promising therapeutic potential of Chinese herbal medicines as viable alternatives in the treatment of depression, with certain herbs demonstrating enhanced efficacy and safety profiles. The outcomes of this study advocate for the integration of these alternative modalities into contemporary depression management paradigms. However, it underscores the necessity for larger, methodologically robust trials to further validate and refine these preliminary findings. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023452109.

Clinical Characteristics and Analysis of Associated Risk Factors in Patients with Severe and Non-Severe COVID-19 Infection.

Objective: Our aim was to highlight the clinical characteristics and determine the risk factors associated with severe and non-severe COVID-19 infection. Study Method: A retrospective review was conducted on clinical data obtained from patients with COVID-19 infection, admitted to the emergency department between November 2022 and January 2023. Total of 1684 participants were categorized into severe (312 cases,18.53%) and non-severe (1,372 cases,81.47%) cohorts. Logistic regression was utilized for multivariate analysis, with a P-value less than 0.05 signifying a significant difference between the groups. Results: The study consisted of 952 males (56.53%) and 732 females (43.47%) participants. The age distribution ranged from 18 to 93 years in both cohorts. There were statistically significant differences between the clinical symptoms of the severe and non-severe cohorts (P < 0.05). According to the multivariate statistical analysis, patients with more pronounced clinical manifestations had significantly elevated values related to age(P < 0.05), diabetes(P < 0.01), hypertension(P < 0.01), C-reactive protein (CRP) (P < 0.05), and lactate dehydrogenase (LDH) (P < 0.01) as compared to those presenting with milder symptoms. Conclusion: The primary clinical presentations in both the cohorts were mostly similar. Predominant factors contributing to the severity of COVID-19 infection were age, diabetes, hypertension, elevated CRP levels, and increased LDH.

Serum proteomic profiling of precancerous gastric lesions and early gastric cancer reveals signatures associated with systemic inflammatory response and metaplastic differentiation.

The noninvasive detection technique using serum for large-scale screening is useful for the early diagnosis of gastric cancer (GC). Herein, we employed liquid chromatography mass spectrometry to determine the serum proteome signatures and related pathways in individuals with gastric precancerous (pre-GC) lesions and GC and explore the effect of Helicobacter pylori (H. pylori) infection. Differentially expressed proteins in GC and pre-GC compared with non-atrophic gastritis (NAG) group were identified. APOA4, a protein associated with metaplastic differentiation, and COMP, an extracellular matrix protein, were increased in the serum of patients with pre-GC lesions and GC. In addition, several inflammation-associated proteins, such as component C3, were decreased in the GC and pre-GC groups, which highlight a tendency for the inflammatory response to converge at the gastric lesion site during the GC cascade. Moreover, the abundance of proteins associated with oxidant detoxification was higher in the GC group compared with that in the NAG group, and these proteins were also increased in the serum of the H. pylori-positive GC group compared with that in the H. pylori-negative GC patients, reflecting the importance of oxidative stress pathways in H. pylori infection. Collectively, the findings of this study highlight pathways that play important roles in GC progression, and may provide potential diagnostic biomarkers for the detection of pre-GC lesions.

Supramolecular salicylic acid combined with niacinamide in chloasma: A randomized controlled trial.

BACKGROUND: No trial of supramolecular salicylic acid (SSA) for chloasma is available yet. OBJECTIVE: The purpose of this study was to assess the efficacy and safety of Bole DA 30% supramolecular salicylic acid (SSA) combined with 10% niacinamide in treating chloasma. METHODS: This multicenter (n=15), randomized, double-blind, parallel placebo-controlled trial randomized the subjects (1:1) to Bole DA 30% SSA or placebo. The primary endpoint was the effective rate after 16 weeks using the modified melasma area severity index (mMASI) [(pretreatment-posttreatment)/pretreatment×100%]. RESULTS: This study randomized 300 subjects (150/group in the full analysis set, 144 and 147 in the per-protocol set). The total mMASI score, overall Griffiths 10 score, left Griffiths 10 score, and right Griffiths 10 score were significantly lower in the Bole DA 30% SSA group than in the placebo group (all P<0.001). One study drug-related AE and one study drug-unrelated adverse events (AE) were reported in the Bole DA 30% SSA group. No AE was reported in the placebo group. CONCLUSION: Bole DA 30% SSA combined with 10% niacinamide is effective and safe for treating chloasma. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2200065346.

Imaging and quantification of neuropeptides in mouse pituitary tissue by atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry.

RATIONALE: Atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) mass spectrometry has enabled the untargeted analysis and imaging of neuropeptides and proteins in biological tissues under ambient conditions. Sensitivity in AP-MALDI can be improved by using sample-specific preparation methods. METHODS: A comprehensive and detailed optimization strategy including instrument parameters, matrix spraying and sample tissue washing pretreatment was implemented to enhance the sensitivity and coverage of neuropeptides in mouse pituitary tissues by commercial AP-MALDI mass spectrometry imaging (MSI). RESULTS: The sensitivity of a commercial AP-MALDI system for endogenous neuropeptides in mouse pituitary was enhanced by up to 15.2-fold by shortening the transmission gap from the sample plate to the inlet, attaching copper adhesive tape to an indium tin oxide-coated glass slide, optimizing the matrix spray solvent and using sample tissue washing pretreatment. Following careful optimization, the distributions of nine endogenous neuropeptides were successfully visualized in the pituitary. Furthermore, the quantitative capability of AP-MALDI for neuropeptides was evaluated and the concentrations of neuropeptides oxytocin and vasopressin in the pituitary posterior lobe were increased approximately twofold under hypertonic saline stress. CONCLUSION: Mouse pituitary neuropeptides have emerged as important signaling molecules due to their role in stress response. This work indicates the potential of modified AP-MALDI as a promising AP MSI method for in situ visualization and quantification of neuropeptides in complex biological tissues.

Imaging features of ALK-positive histiocytosis with neurological involvement: a case report and literature review.

Background: ALK-positive histiocytosis is an exceptionally rare neoplasm of histiocytes that predominantly involves the nervous system and can also affect the skin and other parts of the body. Previous relevant literature has provided limited information regarding the imaging manifestations of this disease with neurological involvement. Methods: We reported a case of ALK-positive histiocytosis with multisystem involvement. Together with a comprehensive literature review, the imaging characteristics of this disease in the nervous system were summarized. Results: A 3-year-old girl with abdominal pain and ambulation difficulty checked in at the Department of Pediatric Neurology. The initial diagnosis was "acute cerebellitis with ataxia" based on the elevated protein level in the cerebrospinal fluid (CSF). However, despite 3 months of treatment, her condition deteriorated. MRI showed an oval-shaped, intradural extramedullary nodule at the T6-T7 level. The patient was ultimately diagnosed as ALK-positive histiocytosis, accompanied by cauda equina and skin involvement. The literature review showed a total of 23 patients who had involvement of the nervous system and provided imaging descriptions. Together with our case, the imaging features were summarized as follows: iso-dense or slightly hyperdense on computed tomography (CT), isointense or iso-hypointense on T2-weighted imaging (T2WI), moderate homogeneous enhancement with mildly/markedly punctate enhancement or/and smooth ring enhancement on contrast-enhanced T1-weighted imaging (T1WI), restricted diffusion on diffuse weighted imaging (DWI), and elevated fluorodeoxyglucose (FDG) uptake on positron-emission tomography/computed tomography (PET/CT). Conclusion: The multimodal imaging findings of ALK-positive histiocytosis exhibit distinct characteristics, familiarity with which will enhance radiologists' expertise and facilitate accurate diagnosis of this disease.

Metabolic and microbial changes in light-vented bulbul during recent northward range expansion.

Endotherms recently expanding to cold environments generally exhibit strong physiological acclimation to sustain high body temperature. During this process, gut microbes likely play a considerable role in host physiological functions, including digestion and thermogenesis. The light-vented bulbul Pycnonotus sinensis represents one such species. It used to be restricted to the Oriental realm but expanded its distribution range north to the Palearctic areas during the past few decades. Here, we explored the seasonal dynamics of the resting metabolic rate (RMR) and microbiota for local and newly colonized populations of the species. Our results showed that the mass-adjusted RMR and body mass were positively correlated with latitude variations in both seasons. Consistently, the gut microbiota showed a corresponding variation to the northern cold environments. In the two northern populations, the alpha diversity decreased compared with those of the two southern populations. Significant differences were detected in dominant phyla, such as Firmicutes, Bacteroidetes, Proteobacteria, and Desulfobacterota in both seasons. The core microbiota showed geographic differences in the winter, including the elevated relative abundance of 5 species in northern populations. Finally, to explore the link between microbial communities and host metabolic thermogenesis, we conducted a correlation analysis between microbiota and mass-adjusted RMR. We found that more genera were significantly correlated with mass-adjusted RMR in the wintering season compared to the breeding season (71 vs. 23). These results suggest that microbiota of the lighted-vented bulbul linked with thermogenesis in diversity and abundance under northward expansion.

Highly Reactive Graphene Dispersant and Its Effective Reinforcement for Phase Change Coatings.

High efficient dispersant that meanwhile possesses additional functions is highly desirable for the fabrication of graphene-based composite. In this paper, a new reactive dispersant, multi-silanols grafted naphthalenediamine (MSiND), is synthesized, which shows superiority compared with conventional dispersants. It can not only stabilize graphene in water at a high concentration of up to 16 mg mL-1 , but also simultaneously be applicable for ethanol medium, in which the graphene concentration can be as high as 12 mg mL-1 at the weight ratio of 1:1 (MSiND:graphene). The dispersion is compatible with multi-matrixes and affinity to various substrates. In addition, MSiND exhibits excellent reactivity due to the existence of high-density silanol groups. Tough graphene coatings are constructed on glass slides and non-woven fabric simply by direct painting and dip-coating. Moreover, with the assistance of MSiND, graphene-doped phase-change coatings on hydrophobic non-woven fabric (e.g., functional mask) are prepared via the spray method. The composite coatings show enhanced mechanical strength and excellent energy storage performance, exhibiting great potential in heat preservation and thermotherapy.

A Novel Grading System for Diffuse Chorioretinal Atrophy in Pathologic Myopia.

INTRODUCTION: This study aims to quantitatively assess diffuse chorioretinal atrophy (DCA) in pathologic myopia and establish a standardized classification system utilizing artificial intelligence. METHODS: A total of 202 patients underwent comprehensive examinations, and 338 eyes were included in the study. The methodology involved image preprocessing, sample labeling, employing deep learning segmentation models, measuring and calculating the area and density of DCA lesions. Lesion severity of DCA was graded using statistical methods, and grades were assigned to describe the morphology of corresponding fundus photographs. Hierarchical clustering was employed to categorize diffuse atrophy fundus into three groups based on the area and density of diffuse atrophy (G1, G2, G3), while high myopic fundus without diffuse atrophy was designated as G0. One-way analysis of variance (ANOVA) and nonparametric tests were conducted to assess the statistical association with different grades of DCA. RESULTS: On the basis of the area and density of DCA, the condition was classified into four grades: G0, G1 (0 < density ≤ 0.093), G2 (0.093 < density ≤ 0.245), and G3 (0.245 < density ≤ 0.712). Fundus photographs depicted a progressive enlargement of atrophic lesions, evolving from punctate-shaped to patchy with indistinct boundaries. DCA atrophy lesions exhibited a gradual shift in color from brown-yellow to yellow-white, originating from the temporal side of the optic disc and extending towards the macula, with severe cases exhibiting widespread distribution throughout the posterior pole. Patients with DCA were significantly older [34.00 (27.00, 48.00) vs 29.00 (26.00, 34.00) years], possessed a longer axial length (28.85 ± 1.57 vs 27.11 ± 1.01 mm), and exhibited a more myopic spherical equivalent [- 13.00 (- 16.00, - 10.50) vs - 9.09 ± 2.41 D] compared to those without DCA (G0) (all P < 0.001). In eyes with DCA, a trend emerged as grades increased from G1 to G3, showing associations with older age, longer axial length, deeper myopic spherical equivalent, larger area of parapapillary atrophy, and increased fundus tessellated density (all P < 0.001). CONCLUSIONS: The novel grading system for DCA, based on assessments of area and density, serves as a reliable measure for evaluating the severity of this condition, making it suitable for widespread application in the screening of pathologic myopia.

Endothelial POFUT1 controls injury-induced liver fibrosis by repressing fibrinogen synthesis.

BACKGROUND & AIMS: NOTCH signaling in liver sinusoidal endothelial cells (LSECs) regulates liver fibrosis, a pathological feature of chronic liver diseases. POFUT1 is an essential regulator of NOTCH signaling. Here, we investigated the role of LSEC-expressed POFUT1 in liver fibrosis. METHODS: Endothelial-specific Pofut1 knockout mice were generated and experimental liver fibrosis was induced by chronic carbon tetrachloride exposure or common bile duct ligation. Liver samples were assessed by ELISA, histology, electron microscopy, immunostaining and RNA in situ hybridization. LSECs and hepatic stellate cells (HSCs) were isolated for gene expression analysis by RNA sequencing, qPCR, and western blotting. Signaling crosstalk between LSECs and HSCs was investigated by treating HSCs with supernatant from LSEC cultures. Liver single-cell RNA sequencing datasets from patients with cirrhosis and healthy individuals were analyzed to evaluate the clinical relevance of gene expression changes observed in mouse studies. RESULTS: POFUT1 loss promoted injury-induced LSEC capillarization and HSC activation, leading to aggravated liver fibrosis. RNA sequencing analysis revealed that POFUT1 deficiency upregulated fibrinogen expression in LSECs. Consistently, fibrinogen was elevated in LSECs of patients with cirrhosis. HSCs treated with supernatant from LSECs of Pofut1 null mice showed exacerbated activation compared to those treated with supernatant from control LSECs, and this effect was attenuated by knockdown of fibrinogen or by pharmacological inhibition of fibrinogen receptor signaling, altogether suggesting that LSEC-derived fibrinogen induced the activation of HSCs. Mechanistically, POFUT1 loss augmented fibrinogen expression by enhancing NOTCH/HES1/STAT3 signaling. CONCLUSIONS: Endothelial POFUT1 prevents injury-induced liver fibrosis by repressing the expression of fibrinogen, which functions as a profibrotic paracrine signal to activate HSCs. Therapies targeting the POFUT1/fibrinogen axis offer a promising strategy for the prevention and treatment of fibrotic liver diseases. IMPACT AND IMPLICATIONS: Paracrine signals produced by liver vasculature play a major role in the development of liver fibrosis, which is a pathological hallmark of most liver diseases. Identifying those paracrine signals is clinically relevant in that they may serve as therapeutic targets. In this study, we discovered that genetic deletion of Pofut1 aggravated experimental liver fibrosis in mouse models. Moreover, fibrinogen was identified as a downstream target repressed by Pofut1 in liver endothelial cells and functioned as a novel paracrine signal that drove liver fibrosis. In addition, fibrinogen was found to be relevant to cirrhosis and may serve as a potential therapeutic target for this devastating human disease.

Homozygous variant in COQ7 causes autosomal recessive hereditary spastic paraplegia.

Biallelic mutations in the coenzyme Q7 (COQ7) encoding gene were recently identified as a genetic cause of distal hereditary motor neuropathy. Here, we explored the clinical, electrophysiological, pathological, and genetic characteristics of a Chinese patient with spastic paraplegia associated with recessive variants in COQ7. This patient carried a novel c.322C>A (p.Pro108Thr) homozygous variant. Sural biopsy revealed mild mixed axonal and demyelinating degeneration. Immunoblotting showed a significant decrease in the COQ7 protein level in the patient's fibroblasts. This study confirmed that COQ7 variant as a genetic cause of HSP, and further extended spastic paraplegia to the phenotypic spectrum of COQ7-related disorders.

Development of Transmission Ambient Pressure Laser Desorption Ionization/Postphotoionization Mass Spectrometry Imaging.

Laser-based high-resolution mass spectrometry imaging at ambient conditions has promising applications in life science. However, the ion yield during laser desorption/ablation is poor. Here, transmission atmospheric pressure laser desorption ionization combined with a compact postphotoionization (t-AP-LDI/PI) assembly with a krypton discharge lamp was developed for the untargeted imaging of various biomolecules. The spatial distributions of numerous lipid classes, fatty acids, neurotransmitters, and amino acids in the subregions of mouse cerebellum tissue were obtained. Compared with single laser ablation, the sensitivities for most analytes were increased by 1 to 3 orders of magnitude by dopant-assisted postphotoionization. After careful optimization, a spatial resolution of 4 µm could be achieved for the metabolites in mouse hippocampus tissue. Finally, the melanoma tissue slices were analyzed using t-AP-LDI/PI MSI, which revealed the metabolic heterogeneity of the melanoma microenvironment and exhibited the phenomenon of abnormal proliferation and invasion trends in tumor cells.

PANoptosis: bridging apoptosis, pyroptosis, and necroptosis in cancer progression and treatment.

This comprehensive review explores the intricate mechanisms of PANoptosis and its implications in cancer. PANoptosis, a convergence of apoptosis, pyroptosis, and necroptosis, plays a crucial role in cell death and immune response regulation. The study delves into the molecular pathways of each cell death mechanism and their crosstalk within PANoptosis, emphasizing the shared components like caspases and the PANoptosome complex. It highlights the significant role of PANoptosis in various cancers, including respiratory, digestive, genitourinary, gliomas, and breast cancers, showing its impact on tumorigenesis and patient survival rates. We further discuss the interwoven relationship between PANoptosis and the tumor microenvironment (TME), illustrating how PANoptosis influences immune cell behavior and tumor progression. It underscores the dynamic interplay between tumors and their microenvironments, focusing on the roles of different immune cells and their interactions with cancer cells. Moreover, the review presents new breakthroughs in cancer therapy, emphasizing the potential of targeting PANoptosis to enhance anti-tumor immunity. It outlines various strategies to manipulate PANoptosis pathways for therapeutic purposes, such as targeting key signaling molecules like caspases, NLRP3, RIPK1, and RIPK3. The potential of novel treatments like immunogenic PANoptosis-initiated therapies and nanoparticle-based strategies is also explored.

Recommended 10-Year Follow-Up Strategy for Small Hepatocellular Carcinoma After Radiofrequency Ablation: A Cost-Effectiveness Evaluation.

INTRODUCTION: An optimal follow-up schedule for small (≤3-cm) hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) remains unclear in clinical guidelines. We aimed to assess the cost-effectiveness of follow-up strategies in patients with small HCC after RFA. METHODS: In total, 11,243 patients were collected from global institutions to calculate recurrence rates. Subsequently, a Markov model covering a 10-year period was developed to compare 25 surveillance strategies involving different surveillance techniques (computed tomography [CT], magnetic resonance imaging or ultrasonography [US], and α-fetoprotein [AFP]) and intervals (3 or 6 months). The study endpoint was incremental cost-effectiveness ratio (ICER), which represented additional cost per incremental quality-adjusted life year. Sensitivity analysis was conducted by varying the values of input parameters to observe the ICER. RESULTS: In a base case analysis, the dominant strategy was CT every 3 months during an initial 2 years, followed by semiannual CT, and then switch to biannual the combination of US screening and AFP testing after 5 years (m3_CT-m6_CT-m6_USAFP), with an ICER of $68,570.92 compared with the "not followed" strategy. One-way sensitivity analysis showed the ICER consistently remained below the willingness-to-pay threshold of $100,000.00. In a probabilistic sensitivity analysis, m3_CT-m6_CT-m6_USAFP was the most cost-effective approach in 95.6% of simulated scenarios at a willingness-to-pay threshold. DISCUSSION: For small HCC after RFA, the recommended follow-up strategy is CT, with scans scheduled every 3 months for the first 2 years, every 6 months thereafter, and transition to biannual the combination of US screening and AFP testing after 5 years.