Difference of carrier dynamics in a semiconductor saturable absorber mirror with and without B+ ion-implantation.

Three samples whose growth temperatures were 450°C, 500°C, and 560°C for S E S A M 1, S E S A M 2, and S E S A M 3, respectively, were tested by femto-second time-resolved transient absorption spectroscopy. The results indicate that the carrier dynamics of excited state absorption were dominant, and the lifetimes of carriers trapped by defect levels were about tens of pico-seconds. To further study the influence of carrier dynamics and recovery time of samples by ion-implantation, B + ions of 80 and 130 KeV were implanted into the samples with dose of 1014/c m 2. The modified samples showed a dominance of ultra-fast carrier dynamics of ground-state bleaching and direct recombination, which lasted for hundreds of femto-seconds, over excited state absorption. Additionally, carrier fast trapping was observed to be competitive with the excited state absorption process. After ion-implantation, the carrier dynamics of carrier trapping were enhanced, which contributed to forming an ultra-short laser, while the carrier dynamics of absorption of the excited state were suppressed. The conclusion that defect levels were partially eliminated by B + ion-implantation can be drawn.

Dissociable dorsal medial prefrontal cortex ensembles are necessary for cocaine seeking and fear conditioning in mice.

The dmPFC plays a dual role in modulating drug seeking and fear-related behaviors. Learned associations between cues and drug seeking are encoded by a specific ensemble of neurons. This study explored the stability of a dmPFC cocaine seeking ensemble over two weeks and its influence on persistent cocaine seeking and fear memory retrieval. In the first series of experiments, we trained TetTag mice in cocaine self-administration and tagged strongly activated neurons with EGFP during the initial day 7 cocaine seeking session. Subsequently, a follow-up seeking test was conducted two weeks later to examine ensemble reactivation between two seeking sessions via c-Fos immunostaining. In the second series of experiments, we co-injected viruses expressing TRE-cre and a cre-dependent inhibitory PSAM-GlyR into the dmPFC of male and female c-fos -tTA mice to enable "tagging" of cocaine seeking ensemble or cued fear ensemble neurons with an inhibitory chemogenetic receptors. Then we investigated their contribution to subsequent cocaine seeking and fear recall during inhibition of the tagged ensemble by administering uPSEM792s (0.3 mg/kg), a selective ligand for PSAM-GlyR. In both sexes, there was a positive association between the persistence of cocaine seeking and the proportion of reactivated EGFP+ neurons within the dmPFC. More importantly, inhibition of the cocaine seeking ensemble suppressed cocaine seeking, but not recall of fear memory, while inhibition of the fear ensemble reduced conditioned freezing but not cocaine seeking. The results demonstrate that cocaine and fear recall ensembles in the dmPFC are stable, but largely exclusive from one another.

Air sampling and ATP bioluminescence for quantitative detection of airborne microbes.

Exposure to bioaerosol contamination has detrimental effects on human health. Recent advances in ATP bioluminescence provide more opportunities for the quantitative detection of bioaerosols. Since almost all active organisms can produce ATP, the amount of airborne microbes can be easily measured by detecting ATP-driven bioluminescence. The accurate evaluation of microorganisms mainly relies on following the four key steps: sampling and enrichment of airborne microbes, lysis for ATP extraction, enzymatic reaction, and measurement of luminescence intensity. To enhance the effectiveness of ATP bioluminescence, each step requires innovative strategies and continuous improvement. In this review, we summarized the recent advances in the quantitative detection of airborne microbes based on ATP bioluminescence, which focuses on the advanced strategies for improving sampling devices combined with ATP bioluminescence. Meanwhile, the optimized and innovative strategies for the remaining three key steps of the ATP bioluminescence assay are highlighted. The aim is to reawaken the prosperity of ATP bioluminescence and promote its wider utilization for efficient, real-time, and accurate detection of airborne microbes.

Detection of pTDP-43 via routine muscle biopsy: A promising diagnostic biomarker for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP-43 aggregates. Recent evidence has been indicated that phosphorylated TDP-43 (pTDP-43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP-43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP-43 detectable in routine biopsied muscles? (ii) Can detection of pTDP-43 aggregation discriminate between ALS and non-ALS patients? (iii) Can pTDP-43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non-ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP-43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP-43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non-ALS controls (16/54; p < 0.001). The pTDP-43 aggregates were mainly close to the sarcolemma. Using a semi-quantified pTDP-43 aggregates score, we applied a cut-off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP-43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof-of-concept for the detection of pTDP-43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS.

Associations of fasting plasma glucose with all-cause mortality and cardiovascular events in older Chinese diabetes patients: A population-based cohort study.

AIMS/INTRODUCTION: Our aim was to investigate the optimal fasting glucose (FPG) range in Chinese older adults with type 2 diabetes, and to clarify whether the optimal range varies according to the control of risk factors. MATERIALS AND METHODS: The baseline survey for the cohort study began in 2018, with follow up ending in 2022. Our study enrolled 59,030 older diabetes patients with no history of cardiovascular disease (CVD). Participants were divided into nine groups based on their baseline glycemic status. The association between FPG and the risk of adverse outcomes was mainly estimated by multivariate Cox proportional risk models and restricted spline analysis. RESULTS: During the 4-year follow-up period, a total of 5,637 deaths and 4,904 CVD events occurred. The associations of FPG with mortality and CVD events showed J-shaped curves. Among all-cause deaths, the hazard ratios for FPG ≤4.50 and >11.50 mmol/L were 1.50 (95% confidence interval [CI] 1.31-1.71) and 1.84 (95% CI 1.67-2.02). Among CVD, the hazard ratios for FPG ≤4.50 and >11.50 mmol/L were 1.31 (95% CI 1.13-1.53) and 1.71 (95% CI 1.54-1.89), respectively. The optimal FPG ranges of all-cause mortality and CVD were 5.50-7.50 and 4.50-7.50 mmol/L, respectively. For participants with at least two risk factors, the optimal FPG levels were higher than those with fewer risk factors. CONCLUSIONS: In older Chinese diabetes patients, the FPG ranges related to the minimum death and CVD event rates were 5.50-7.50 and 4.50-7.50 mmol/L, respectively. Patients with more cardiovascular risk factors had higher optimal blood glucose ranges than those with fewer risk factors.

Efficacy and survival outcomes of alectinib vs. crizotinib in ALK­positive NSCLC patients with CNS metastases: A retrospective study.

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have transformed the treatment paradigm for patients with ALK-positive non-small cell lung cancer (NSCLC). Yet the differential efficacy between alectinib and crizotinib in treating patients with NSCLC and central nervous system (CNS) metastases has been insufficiently studied. A retrospective analysis was conducted of clinical outcomes of patients with ALK-positive NSCLC and CNS metastases treated at the Shandong Cancer Centre. Based on their initial ALK-TKI treatment, patients were categorised into either the crizotinib group or the alectinib group. Efficacy, progression-free survival (PFS), intracranial PFS and overall survival (OS) were evaluated. A total of 46 eligible patients were enrolled in the present study: 33 patients received crizotinib and 13 patients received alectinib. The median OS of the entire group was 66.8 months (95% CI: 48.5-85.1). Compared with the patients in the crizotinib group, the patients in the alectinib group showed a significant improvement in both median (m)PFS (27.5 vs. 9.5 months; P=0.003) and intracranial mPFS (36.0 vs. 10.8 months; P<0.001). However, there was no significant difference in OS between the alectinib and crizotinib groups (not reached vs. 58.7 months; P=0.149). Furthermore, there were no significant differences between patients receiving TKI combined with radiotherapy (RT) vs. TKI alone with respect to mPFS (11.0 vs. 11.7 months, P=0.863) as well as intracranial mPFS (12.5 vs. 16.9 months, P=0.721). In the present study, alectinib exhibited superior efficacy to crizotinib for treating patients with ALK-positive NSCLC and CNS metastases, especially in terms of delaying disease progression and preventing CNS recurrence. Moreover, the results demonstrated that it might be beneficial to delay local RT for patients with ALK-positive NSCL and CNS metastases.

The roles of 5-HT in orofacial pain.

OBJECTIVES: Acute and chronic orofacial pain are very common and remain a vexing health problem that has a negative effect on the quality of life. Serotonin (5-HydroxyTryptamine, 5-HT) is a kind of monoamine neurotransmitter that is involved in many physiological and pathological processes. However, its role in orofacial pain remains inconclusive. Therefore, this review aims to summarize the recent advances in understanding the effect exerted by 5-HT on the modulation of orofacial pain. SUBJECTS AND METHODS: An extensive search was conducted on PubMed and Web of Science for pertinent studies focusing on the effects of 5-HT on the modulation of orofacial pain. RESULTS: In this review, we concisely review how 5-HT mediates orofacial pain, how 5-HT is regulated and how we can translate these findings into clinical applications for the prevention and/or treatment of orofacial pain. CONCLUSIONS: 5-HT plays a key role in the modulation of orofacial pain, implying that 5-HT modulators may serve as effective treatment for orofacial pain. However, further research on the precise mechanisms underlying the modulation of orofacial pain is still warranted.

The genus Ranunculus L. (Ranunculus) in Asia: a review of its botany, traditional uses, phytochemistry, pharmacology, toxicity, and pharmaceutical preparations.

OBJECTIVES: Ranunculus L. genus contains 413 species, and it is the biggest genus in the family Ranunculaceae Juss. This review is to provide botanical characteristics, traditional uses, phytochemistry, pharmacology, toxicity, and pharmaceutical preparations of the genus Ranunculus. KEY FINDINGS: The genus Ranunculus contains flavonoids, organic acids, coumarins, lactones, glycosides, sterols, polysaccharides, and trace elements. These chemical constituents complement the pharmacological actions and work together to exert anti-inflammatory, anticancer, antitubercular, antibacterial, antimalarial, etc. Those traditional Chinese medicine characteristics, like clearing away heat and detoxification, make this genus significant in ethnic medicine. The progress in research and the development of various pharmaceutical preparations made it appear in epidemiological and clinical studies. SUMMARY: The genus Ranunculus has attracted the attention of experts and scholars in many fields due to its unique advantages. However, there are many species that are not scientifically investigated. The toxicity issues are also a huge concern. Fortunately, the toxicity can be overcome via special processes like drying or heating and by choosing a safe extraction solvent, such as water thus ensuring the safety of medication. Pharmaceutical preparations containing the plants from Ranunculus have gratifying clinical value, but they are not promoted sufficiently. Therefore, further research should be carried out to promote the genus for its health benefits to humans.

Neural mechanisms of different types of envy: a meta-analysis of activation likelihood estimation methods for brain imaging.

Previous studies have a lack of meta-analytic studies comparing the trait (personality) envy, social comparison envy, and love-envy, and the understanding of the similarities and differences in the neural mechanisms behind them is relatively unclear. A meta-analysis of activation likelihood estimates was conducted using 13 functional magnetic resonance imaging studies. Studies first used single meta-analyses to identify brain activation areas for the three envy types. Further, joint and comparative analyses were followed to assess the common and unique neural activities among the three envy types. A single meta-analysis showed that the critical brain regions activated by trait (personality) envy included the inferior frontal gyrus, cingulate gyrus, middle frontal gyrus, lentiform nucleus and so on. The critical brain regions activated by social comparison envy included the middle frontal gyrus, inferior frontal gyrus, medial frontal gyrus, precuneus and so on. The critical brain regions activated by love-envy included the inferior frontal gyrus, superior frontal gyrus, cingulate gyrus, insula and so on. In terms of the mechanisms that generate the three types of envy, each of them is unique when it comes to the perception of stimuli in a context; in terms of the emotion regulation mechanisms of envy, the three types of envy share very similar neural mechanisms. Both their generation and regulation mechanisms are largely consistent with the cognitive control model of emotion regulation. The results of the joint analysis showed that the brain areas co-activated by trait (personality) envy and social comparison envy were frontal sub-Gyral, inferior parietal lobule, inferior frontal gyrus, precuneus and so on; the brain areas co-activated by trait (personality) envy and love-envy were extra-nuclear lobule, lentiform nucleus, paracentral lobule, cingulate gyrus and so on; the brain regions that are co-activated by social comparison envy and love-envy are anterior cingulate gyrus, insula, supramarginal gyrus, inferior frontal gyrus and so on. The results of the comparative analysis showed no activation clusters in the comparisons of the three types of envy.

Sensitive organic/inorganic polarized photodetectors enhanced by charge transfer with image sensing capacity.

Organic photodetectors (OPDs) have attracted increasing attention in the future wearable sensing and real-time health monitoring, due to their intrinsic features including the mechanical flexibility, low-cost processing and cooling-free operations; while their performances are lagging as the results of inferior carrier mobility and small exciton diffusion coefficient of organic molecules. Graphene exhibits the great photoresponse with wide spectral bandwidth and high response speed. However, weak light absorption and the absence of a gain mechanism have limited its photoresponsivity. Here, we report a sensitive organic/inorganic phototransistor with fast response speed by coupling PTCDA organic single crystal with the monolayer graphene. The long range exciton diffusion in highly ordered π-conjugated molecules, efficient exciton dissociation and charge transfer at the PTCDA/graphene heterointerfaces, and the high mobility of graphene enable a high responsivity (8 × 104A/W), short response time (220 µs) and excellent specific detectivity (>1011 Jones), which is higher than the level of commercial on-chip device. This interfacial photogating effect is verified by the high-resolution spatial photocurrent mapping experiment. In addition, the high sensitivity to polarization is clear and the ultrahigh photoconductive gain enables a near-infrared (NIR) response for 980 and 1550 nm. Finally, high-speed visible and NIR imaging applications are successfully demonstrated. This work suggests that high quality organic single crystal/graphene is a promising platform for future high performance optoelectronic systems and imaging applications.

X chromosome rearrangement associated with premature ovarian insufficiency as diagnosed by molecular cytogenetic methods: a case report and review of the literature.

BACKGROUND: Premature ovarian insufficiency (POI) is a clinical condition characterized by ovarian dysfunction in women under 40. The etiology of most POI cases remains unidentified and is believed to be multifactorial, including factors such as autoimmunity, metabolism, infection, and genetics. POI exhibits significant genetic heterogeneity, and it can result from chromosomal abnormalities and monogenic defects. CASE PRESENTATION: The study participant, a 33-year-old woman, presented with a history of irregular menstruation that commenced two years ago, progressing to prolonged menstrual episodes and eventual cessation. The participant exhibits a rearrangement of the X chromosome, characterized by heterozygosity duplication on the long arm and heterozygosity deletion on the short arm by whole exome sequencing(WES) combined with cell chromosome detection. CONCLUSIONS: This study expands the spectrum of mutations associated with POI resulting from X chromosomal abnormalities. WES-Copy number variation analysis, in conjunction with chromosome karyotype analysis and other detection techniques, can provide a more comprehensive understanding of the genetic landscape underlying complex single or multi-system diseases.

Verteporfin fluorescence in antineoplastic-treated pancreatic cancer cells found concentrated in mitochondria.

BACKGROUND: Traditional treatments for pancreatic cancer (PC) are inadequate. Photodynamic therapy (PDT) is non-invasive, and proven safe to kill cancer cells, including PC. However, the mitochondrial concentration of the photosensitizer, such as verteporfin, is key. AIM: To investigate the distribution of fluorescence of verteporfin in PC cells treated with antitumor drugs, post-PDT. METHODS: Workable survival rates of PC cells (AsPC-1, BxPC-3) were determined with chemotherapy [doxorubicin (DOX) and gemcitabine (GEM)] and non-chemotherapy [sirolimus (SRL) and cetuximab (CTX)] drugs in vitro, with or without verteporfin, as measured via MTT, flow cytometry, and laser confocal microscopy. Reduced cell proliferation was associated with GEM that was more enduring compared with DOX. Confocal laser microscopy allowed observation of GEM- and verteporfin-treated PC cells co-stained with 4',6-diamidino-2-phenylindole and MitoTracker Green to differentiate living and dead cells and subcellular localization of verteporfin, respectively. RESULTS: Cell survival significantly dropped upon exposure to either chemotherapy drug, but not to SRL or CTX. Both cell lines responded similarly to GEM. The intensity of fluorescence was associated with the concentration of verteporfin. Additional experiments using GEM showed that survival rates of the PC cells treated with 10 µmol/L verteporfin (but not less) were significantly lower relative to nil verteporfin. Living and dead stained cells treated with GEM were distinguishable. After GEM treatment, verteporfin was observed primarily in the mitochondria. CONCLUSION: Verteporfin was observed in living cells. In GEM -treated human PC cells, verteporfin was particularly prevalent in the mitochondria. This study supports further study of PDT for the treatment of PC after neoadjuvant chemotherapy.

Cyclin B1: A potential prognostic and immunological biomarker in pan-cancer.

Cyclin B1 (CCNB1) encodes a regulatory protein essential for the regulation of cell mitosis, particularly in controlling the G2/M transition phase of the cell cycle. Current research has implicated CCNB1 in the progression of various types of cancer, including gastric cancer, breast cancer, and non-small cell lung cancer. In this study, we conducted a pan-cancer analysis of CCNB1 to investigate its prognostic significance and immunological aspects. Our comprehensive investigation covered a wide range of analyses, including gene expression, promoter methylation, genetic alterations, immune infiltration, immune regulators, and enrichment studies. We utilized multiple databases and tools for this purpose, such as The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx) project, the Human Protein Atlas (HPA), the University of Alabama at Birmingham CANcer data analysis Portal (UALCAN), the Gene Expression Profiling Interactive Analysis (GEPIA), the DNA Methylation Interactive Visualization Database (DNMIVD), the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Sangerbox, and cBioPortal. Data analyses were executed using GraphPad Prism software, R software, and various online tools. Our findings demonstrated a significant increase in CCNB1 expression across 28 cancer types. Elevated CCNB1 expression correlated with decreased overall survival (OS) in 11 cancer types and disease-free survival (DFS) in 12 cancer types. Additionally, DNA promoter methylation levels were significantly decreased in 14 cancer types. Furthermore, the study verified a significant association between CCNB1 expression and immune infiltration, immune modulators, microsatellite instability (MSI), and tumor mutational burden (TMB). Enrichment analysis indicated that CCNB1 is involved in multiple cellular pathways. Collectively, our results suggested that CCNB1 has the potential to serve as a valuable prognostic biomarker and may be a promising target for immunotherapy in various cancer types.

Understanding PI3K/Akt/mTOR signaling in squamous cell carcinoma: mutated PIK3CA as an example.

Compared with those in adenocarcinoma, PIK3CA mutations are more common in squamous cell carcinoma (SCC), which arises from stratified squamous epithelia that are usually exposed to adverse environmental factors. Although hotspot mutations in exons 9 and 20 of PIK3CA, including E542K, E545K, H1047L and H1047R, are frequently encountered in the clinic, their clinicopathological meaning remains to be determined in the context of SCC. Considering that few reviews on PIK3CA mutations in SCC are available in the literature, we undertook this review to shed light on the clinical significance of PIK3CA mutations, mainly regarding the implications and ramifications of PIK3CA mutations in malignant cell behavior, prognosis, relapse or recurrence and chemo- or radioresistance of SCC. It should be noted that only those studies regarding SCC in which PIK3CA was mutated were cherry-picked, which fell within the scope of this review. However, the role of mutated PIK3CA in adenocarcinoma has not been discussed. In addition, mutations occurring in other main members of the PI3K-AKT-mTOR signaling pathway other than PIK3CA were also excluded.

Exacerbating effects of circadian rhythm disruption on the systemic lupus erythematosus.

OBJECTIVE: Circadian rhythm disruption (CRD) has been associated with inflammation and immune disorders, but its role in SLE progression is unclear. We aimed to investigate the impact of circadian rhythms on immune function and inflammation and their contribution to SLE progression to lupus nephritis (LN). METHODS: This study retrospectively analysed the clinical characteristics and transcriptional profiles of 373 samples using bioinformatics and machine-learning methods. A flare risk score (FRS) was established to predict overall disease progression for patients with lupus. Mendelian randomisation was used to analyse the causal relationship between CRD and SLE progression. RESULTS: Abnormalities in the circadian pathway were detected in patients with SLE, and lower enrichment levels suggested a disease state (normalised enrichment score=0.6714, p=0.0062). The disruption of circadian rhythms was found to be closely linked to lupus flares, with the FRS showing a strong ability to predict disease progression (area under the curve (AUC) of 5-year prediction: 0.76). The accuracy of disease prediction was improved by using a prognostic nomogram based on FRS (AUC=0.77). Additionally, Mendelian randomisation analysis revealed an inverse causal relationship between CRD and SLE (OR 0.6284 (95% CI 0.3630 to 1.0881), p=0.0485) and a positive causal relationship with glomerular disorders (OR 0.0337 (95% CI 1.634e-3 to 6.934e-1), p=0.0280). CONCLUSION: Our study reveals that genetic characteristics arising from CRD can serve as biomarkers for predicting the exacerbation of SLE. This highlights the crucial impact of CRD on the progression of lupus.

An effective strategy for assembling the sex-limited chromosome.

BACKGROUND: Most currently available reference genomes lack the sequence map of sex-limited (such as Y and W) chromosomes, which results in incomplete assemblies that hinder further research on sex chromosomes. Recent advancements in long-read sequencing and population sequencing have provided the opportunity to assemble sex-limited chromosomes without the traditional complicated experimental efforts. FINDINGS: We introduce the first computational method, Sorting long Reads of Y or other sex-limited chromosome (SRY), which achieves improved assembly results compared to flow sorting. Specifically, SRY outperforms in the heterochromatic region and demonstrates comparable performance in other regions. Furthermore, SRY enhances the capabilities of the hybrid assembly software, resulting in improved continuity and accuracy. CONCLUSIONS: Our method enables true complete genome assembly and facilitates downstream research of sex-limited chromosomes.

Removal and reduction mechanism of Cr (VI) in Leersia hexandra Swartz constructed wetland-microbial fuel cell coupling system.

Cr (VI) is extremely harmful to both the environment and human health, and it can linger in the environment for a very long period. In this research, the Leersia hexandra Swartz constructed wetland-microbial fuel cell (CW-MFC) system was constructed to purify Cr (VI) wastewater. By comparing with the constructed wetland (CW) system, the system electricity generation, pollutants removal, Cr enrichment, and morphological transformation of the system were discussed. The results demonstrated that the L. hexandra CW-MFC system promoted removal of pollutants and production of electricity of the system. The maximum voltage of the system was 499 mV, the COD and Cr (VI) removal efficiency was 93.73% and 97.00%. At the same time, it enhanced the substrate and L. hexandra ability to absorb Cr and change it morphologically transformation. Additionally, the results of XPS and XANES showed that the majority of the Cr in the L. hexandra and substrate was present as Cr (III). In the L. hexandra CW-MFC system, Geobacter also functioned as the primary metal catabolic reducing and electrogenic bacteria. As a result, L. hexandra CW-MFC system possesses the added benefit of removing Cr (VI) while producing energy compared to the traditional CW system.

Right superior frontal gyrus: A potential neuroimaging biomarker for predicting short-term efficacy in schizophrenia.

Antipsychotic drug treatment for schizophrenia (SZ) can alter brain structure and function, but it is unclear if specific regional changes are associated with treatment outcome. Therefore, we examined the effects of antipsychotic drug treatment on regional grey matter (GM) density, white matter (WM) density, and functional connectivity (FC) as well as associations between regional changes and treatment efficacy. SZ patients (n = 163) and health controls (HCs) (n = 131) were examined by structural magnetic resonance imaging (sMRI) at baseline, and a subset of SZ patients (n = 77) were re-examined after 8 weeks of second-generation antipsychotic treatment to assess changes in regional GM and WM density. In addition, 88 SZ patients and 81 HCs were examined by resting-state functional MRI (rs-fMRI) at baseline and the patients were re-examined post-treatment to examine FC changes. The Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) were applied to measure psychiatric symptoms and cognitive impairments in SZ. SZ patients were then stratified into response and non-response groups according to PANSS score change (≥50 % decrease or <50 % decrease, respectively). The GM density of the right cingulate gyrus, WM density of the right superior frontal gyrus (SFG) plus 5 other WM tracts were reduced in the response group compared to the non-response group. The FC values between the right anterior cingulate and paracingulate gyrus and left thalamus were reduced in the entire SZ group (n = 88) after treatment, while FC between the right inferior temporal gyrus (ITG) and right medial superior frontal gyrus (SFGmed) was increased in the response group. There were no significant changes in regional FC among the non-response group after treatment and no correlations with symptom or cognition test scores. These findings suggest that the right SFG is a critical target of antipsychotic drugs and that WM density and FC alterations within this region could be used as potential indicators in predicting the treatment outcome of antipsychotics of SZ.

Clinical difference on the variants and co-mutation in a Chinese cohort with ALK-positive advanced non-small cell lung cancer.

PURPOSE: Despite the generally favourable prognoses observed in patients with ALK-positive non-small cell lung cancer (NSCLC), there remains significant variability in clinical outcomes. The objective of this study is to enhance patient stratification by examining both the specific sites of gene fusion and the presence of co-occurring mutations. METHODS: We collected retrospective clinical and pathological data on ALK-positive patients with locally advanced or metastatic disease. ALK fusion variants and concomitant mutations were identified through next-generation sequencing technology. We then assessed treatment efficacy via tumor response and survival metrics. RESULTS: This study included a total of 59 patients, with 49 harboring echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusions and 10 presenting with rare fusions. The median follow-up period was 33 months. Clinical outcomes between non-EML4-ALK and EML4-ALK patients were comparable. Among the EML4-ALK cohort, patients with longer variants (v1, v2, v8) demonstrated superior progression-free survival (PFS) (median PFS: 34 months vs. 11 months; hazard ratio [HR]: 2.28; P = 0.05) compared to those with shorter variants (v3, v5). Furthermore, patients treated with second-generation ALK inhibitors (ALKi) displayed a progression-free survival advantage (median PFS: not reached [NR] vs. 9 months; HR: 5.37; P = 0.013). Baseline TP53 co-mutation were linked with a substantially shorter OS (median OS,37 months vs. NR; HR 2.74; P = 0.047). CONCLUSIONS: In ALK+ NSCLC, longer EML4-ALK variants correlate with improved prognosis and enhanced response to second-generation ALKi, while TP53 co-mutations indicate a negative prognosis.

Lead Optimization of Butyrolactone I as an Orally Bioavailable Antiallergic Agent Targeting FcγRIIB.

Food allergy (FA) poses a growing global food safety concern, yet no effective cure exists in clinics. Previously, we discovered a potent antifood allergy compound, butyrolactone I (BTL-I, 1), from the deep sea. Unfortunately, it has a very low exposure and poor pharmacokinetic (PK) profile in rats. Therefore, a series of structural optimizations toward the metabolic pathways of BTL-I were conducted to provide 18 derives (2-19). Among them, BTL-MK (19) showed superior antiallergic activity and favorable pharmacokinetics compared to BTL-I, being twice as potent with a clearance (CL) rate of only 0.5% that of BTL-I. By oral administration, Cmax and area under the concentration-time curve (AUC0-∞) were 565 and 204 times higher than those of BTL-I, respectively. These findings suggest that butyrolactone methyl ketone (BTL-BK) could serve as a drug candidate for the treatment of FAs and offer valuable insights into optimizing the druggability of lead compounds.