Prognostic significance of PET/CT and its association with immuno-genomic profiling in oesophageal squamous cell carcinoma treated with immunotherapy plus chemoradiotherapy: results from a phase II study.

BACKGROUND: A phase II trial (EC-CRT-001) demonstrated the promising efficacy of combining toripalimab (an anti-PD-1 antibody) with definitive chemoradiotherapy (CRT) for locally advanced oesophageal squamous cell carcinoma (ESCC). Biomarkers are key to identifying patients who may benefit from this therapeutic approach. METHODS: Of the 42 patients with ESCC who received toripalimab combined with definitive CRT, 37 were included in this analysis. Baseline assessments included PET/CT metabolic parameters (SUVmax, SUVmean, SUVpeak, MTV, and TLG), RNA sequencing of tumour biopsies to quantify the tissue mutational burden (TMB), and multiplex immunofluorescence staining to estimate immune cell infiltration in the tumour microenvironment (TME). Frozen neoplastic samples were procured for RNA sequencing to further explore the immune-related TME. RESULTS: Among the 37 patients, high baseline SUVmax (≥12.0; OR = 6.5, 95% CI 1.4-48.2, p = 0.032) and TLG (≥121.8; OR = 6.8, 95% CI 1.6-33.5, p = 0.012) were significantly correlated with lower complete response rates. All five PET/CT parameters were notably associated with overall survival; only SUVmax and TLG were associated with a significantly worse progression-free survival. A trend towards an inverse correlation was observed between SUVmax and TMB (R = -0.33, p = 0.062). PD-1 + CD8 + T cell infiltration was negatively correlated with MTV (R = -0.355, p = 0.034) and TLG (R = -0.385, p = 0.021). Moreover, RNA sequencing revealed that the high TLG subgroup exhibited low immune cell infiltration, indicating an immunosuppressive landscape. CONCLUSIONS: High baseline SUVmax and TLG might predict poorer treatment response and worse survival in patients with ESCC undergoing immunotherapy combined with CRT. In addition, high PET/CT metabolic parameters, particularly TLG, were correlated with an immunosuppressive TME, which warrants further exploration.

Comparison of efficacy and safety of combined chemoimmunotherapy with or without radiotherapy for stage IVB esophageal squamous cell carcinoma: a multicenter propensity score matching analysis.

PURPOSE: This study aimed to compare the efficacy and safety of combining first-line chemoimmunotherapy with radiotherapy versus chemoimmunotherapy alone in patients with stage IVB esophageal squamous cell carcinoma (ESCC). METHODS: We retrospectively examined 409 patients with stage IVB ESCC who received first-line chemotherapy and anti-PD-1 antibody, with or without radiotherapy of ≥ 40 Gy radiation dose to primary lesion, from four academic cancer centers between October 2018 and December 2022. Propensity score matching (PSM) was conducted to minimize the potential confounding effects. RESULTS: In the overall cohort of 409 patients, the group that received additional radiotherapy had superior overall survival (OS) (hazard ratio [HR]: 0.51, 95% confidence interval [CI]: 0.39-0.66, P < 0.001) and progression-free survival (PFS) (HR: 0.52, 95% CI: 0.40-0.66, P < 0.001) compared to the group that received chemoimmunotherapy alone. After 1:1 PSM, matching age, tumor location, and metastatic sites, a total of 250 patients were selected for further analysis. The results remained consistent and showed that the addition of radiotherapy significantly improved OS and PFS (median OS: 24.9 vs. 14.6 months, P = 0.003; median PFS: 14.2 vs. 10.6 months, P = 0.002). Multivariate Cox analysis including tumor location, T stage, metastatic sites, and treatment modality, revealed that radiotherapy was an independent prognostic factor for both OS (HR: 0.57, 95% CI: 0.41-0.81) and PFS (HR: 0.63, 95% CI: 0.47-0.86). Subgroup analyses revealed significant OS prolongation in patients with non-regional lymph node metastases only who received radiotherapy (HR: 0.49, 95% CI: 0.34-0.70). No OS survival benefit was observed in those with distant organ metastases (HR: 0.72, 95% CI: 0.46-1.13). Regarding safety, the group receiving additional radiotherapy had higher incidences of grade 3-4 lymphopenia (74.4% vs. 17.7%, P < 0.001) and esophagitis (11.2% vs. 2.4%, P = 0.006). CONCLUSION: The addition of radiotherapy to chemoimmunotherapy improved the survival of stage IVB ESCC patients with non-regional lymph nodes metastasis.

The First Report of Tritrichomonas Foetus and Tetratrichomonas Buttreyi in Raccoon Dogs (Nyctereutes Procyonoides) in China.

BACKGROUND: In recent years, the trichomonosis in raccoon dogs in China had occurred frequently. Pentatrichomonas hominis had been described in raccoon dogs in China in some previous studies. PURPOSE TO REVEAL: whether raccoon dogs can be infected by other trichomonad species besides P. hominis, and clarify the prevalence and species distribution of trichomonad in raccoon dogs. METHODS: Herein, the 389 fecal samples were collected from farm-raised raccoon dogs in Hebei Province, all the samples were detected using the microscopic examination and several fecal samples containing trichomonad-like organisms were processed, cultured, stained, and photographed. Meanwhile, all the samples were screened by the species-specific nested PCR based on the small subunit rRNA (SSU rRNA) gene of P. hominis,Tritrichomonas foetus and Tetratrichomonas buttreyi, respectively, and all positive secondary PCR amplications obtained in this study were sequenced, aligned and analysed. RESULTS: 62 fecal samples (15.9%,62/389) were trichomonad-positive under light microscopy, and the trichomonad-like cells were clearly observed in the culture contents. The PCR results showed that 100 samples were trichomonad-positive, including 45 P. hominis-positive samples (11.6%,45/389), 32 T. foetus-positive samples (8.2%,32/389), and 33 T. buttreyi-positive samples (8.5%,33/389), respectively. Double mixed infections were observed in 10 samples. The prevalence of T. foetus and P. hominis were both significantly higher in raccoon dogs with diarrhea (13.9%, and 25.0%) than that in raccoon dogs without diarrhea (7.6%, and 9.3%) (p < 0.05).All samples confirmed as trichomonad-positive under microscopy were also found to be trichomonad-positive by PCR analysis. The sequencing and phylogenetic analysis demonstrated the sequences obtained in this study belonged to P. hominis, T. foetus and T. buttreyi SSU rRNA, respectively. Among them, the T. buttreyi SSU rRNA sequences obtained in this study harbored the new sequence polymorphisms. Based on preliminary morphological and molecular analyses, raccoon dogs are considered as the new host of T. foetus and T. buttreyi. CONCLUSION: This is the first report about the identifcation and prevalence of T. foetus and T. buttreyi in raccoon dogs in China, and the results increase our knowledge about the host range and prevalence of trichomonad species.

Family quality of life of parents of children with intellectual disability: Do psychological stress and parental involvement matter?

Background: The psychological stress of parents and improving family quality of life (FQoL) are continuing concerns for families of children with intellectual disability. We need to identify further ways to reduce their stress and improve their FQoL in China. Method: Examine the interrelations between psychological stress, parental involvement, and FQoL for parents with intellectual disability in mainland China. 467 parents of children with intellectual disability completed instruments measuring variables. Structural equation modelling (SEM) was employed to examine the interrelations. Results: Psychological stress, directly and indirectly, influenced parental involvement in FQoL. Physical and mental response (PMR) and risk awareness (RA) had a positive direct effect on FQoL, and optimistic hope (OH) had a negative effect on FQoL. Conclusions: Psychological stress affects FQoL of parents with children with intellectual disability in complex ways. Policies should be developed to help parents with children with disability decrease stress and develop scientific parental involvement.

A developed and validated centrifugal ultrafiltration coupled with high performance liquid chromatography-tandem mass spectrometry method for rapid quantification of unbound lenvatinib in human plasma.

In clinical practice, the determination of unbound drug concentration is very important for dose adjustment and toxicity prediction because only the unbound fraction can achieve a pharmacological effect. A fast, sensitive and accurate analytical method of centrifugal ultrafiltration coupled with high performance liquid chromatography-tandem mass spectrometry method was developed and applied to allow the quantification of unbound lenvatinib concentration. The application of linear regression analysis was used to examine the effects of centrifugal force, centrifugal time, and protein content on ultrafiltrate volume (Vu). The results indicated that the centrifugal force and centrifugal time have an influence on Vu that is significantly positive (P < 0.05). This developed method with good linearity (r2 = 0.9996), good accuracy (bias % ≤ 2.24 %), good precision (CV % ≤ 7.10 %), and good recovery (95.46 %-106.46 %) was suitable for routine clinical practice and studies. Particularly, the ultrafiltration membrane had no non-specific binding to lenvatinib. The unbound fractions can be separated in just 15 min. This method was applied to quantify clinical samples and to determine the plasma protein binding and unbound fraction of lenvatinib. This study provides a more effective and promising method for determination of unbound lenvatinib. It could be beneficial to measure the unbound concentration of lenvatinib in personalized medicine and therapeutic drug monitoring in routine clinical practice.

Treatment for middle cerebral artery bifurcation aneurysms: in silico comparison of the novel Contour device and conventional flow-diverters.

Endovascular treatment has become the standard therapy for cerebral aneurysms, while the effective treatment for middle cerebral artery (MCA) bifurcation aneurysms remains a challenge. Current flow-diverting techniques with endovascular coils cover the aneurysm orifice as well as adjacent vessel branches, which may lead to branch occlusion. Novel endovascular flow disruptors, such as the Contour device (Cerus Endovascular), are of great potential to eliminate the risk of branch occlusion. However, there is a lack of valid comparison between novel flow disruptors and conventional (intraluminal) flow-diverters. In this study, two in silico MCA bifurcation aneurysm models were treated by specific Contour devices and flow-diverters using fast-deployment algorithms. Computational fluid dynamic simulations were used to examine the performance and efficiency of deployed devices. Hemodynamic parameters, including aneurysm inflow and wall shear stress, were compared among each Contour device, conventional flow-diverter, and untreated condition. Our results show that the placement of devices can effectively reduce the risk of aneurysm rupture, while the deployment of a Contour device causes more flow reduction than using flow-diverters (e.g. Silk Vista Baby). Besides, the Contour device presents the flow diversion capability of targeting the aneurysm neck without occluding the daughter vessel. In summary, the in silico aneurysm models presented in this study can serve as a powerful pre-planning tool for testing new treatment techniques, optimising device deployment, and predicting the performance in patient-specific aneurysm cases. Contour device is proved to be an effective treatment of MCA bifurcation aneurysms with less daughter vessel occlusion.

Unraveling the photochemical behavior of dissolved organic matter derived from hydrothermal carbonization process water: Insights from molecular transformation and photoactive species.

Hydrothermal carbonization process water (HTPW) has been utilized as a substitute for chemical fertilizers in agricultural applications. However, the input of HTPW into paddy water, particularly the significant proportion of dissolved organic matter (DOM) in HTPW (DOM-HTPW), directly engages in photochemical transformations, a phenomenon often overlooked. This study observed a consistent decrease in humification (SUVA280, 7.7-53.9%) and aromaticity (SUVA254, 6.1-40.0%) of DOM-HTPW after irradiation. The primary active photobleaching components of DOM-HTPW varied depending on the feedstock, such as protein for chicken manure DOM-HTPW and lignin for rice straw DOM-HTPW. The photochemical activity of DOM-HTPW was augmented by its lower molecular weight and higher hydrophilic composition, particularly evident in chicken manure DOM-HTPW, which exhibited higher generation rates for 1O2 (35.1-37.1%), 3DOM* (32.8-43.9%), and O2•- (28.6-48.8%) as measured by molecular probes. DOM-HTPW effectively facilitated the phototransformation of tetracycline, with the contribution of O2•- being more significant than 3DOM* and 1O2. These findings shed new light on the understanding the photochemical processes of DOM-HTPW as exogenous DOM and the interconnected fate of contaminants in aquatic environments.

A case control study of vNOTES hysterectomy with the da Vinci surgical system and conventional vNOTES hysterectomy.

The aim of the case control study was to compare surgical outcomes of transvaginal natural orifice transluminal endoscopic surgery (vNOTES) hysterectomy with the da Vinci surgical system (dVSS) and conventional vNOTES. A case control study was performed on 25 cases in our hospital. Patients (n = 8) who underwent vNOTES hysterectomy with dVSS were selected to compare with the control group (n = 17) consisted of patients who underwent conventional vNOTES. Patients in the 2 groups underwent different operations respectively, and no case was transferred to transabdominal laparoscopy. In the conventional vNOTES group, 1 patient happened intraoperative hemorrhage of about 1000 mL, and was treated with blood transfusion, and the other one of vNOTES hysterectomy with dVSS had poor incision healing within 1 month after surgery. The other patients had no intraoperative and postoperative complications. The difference of pain scores on the first day (P = .006) and the third day (P = .045) after the 2 surgical methods differed significantly. No statistical differences were observed in operation time, median hospital stay, blood loss, decreased hemoglobin 3 days after surgery, and postoperative white blood cell count. vNOTES hysterectomy with dVSS is safe and feasible, and can achieve the same effect as the conventional vNOTES hysterectomy. And this method may alleviate the pain of patients.

Predictive role of ctDNA in esophageal squamous cell carcinoma receiving definitive chemoradiotherapy combined with toripalimab.

The combination of toripalimab (an anti-PD-1 antibody) with definitive chemoradiotherapy (CRT) demonstrated encouraging efficacy against locally advanced esophageal squamous cell carcinoma (ESCC) in the EC-CRT-001 phase II trial (NCT04005170). The primary endpoint of this trial was the clinical complete response rate (cCR), and the secondary endpoints included overall survival (OS), progression-free survival (PFS), duration of response, and quality of life. The exploratory analyses of EC-CRT-001 include exploring the role of circulating tumor DNA (ctDNA) and blood-based tumor mutational burden (bTMB) in predicting the response and survival. In total, 118 blood and 35 tissue samples from 42 enrolled patients were included in the analyses. We found that ctDNA-negative patients achieved a higher cCR compared to those with detectable ctDNA during CRT (83%, 19/23 vs. 39%, 7/18; p = 0.008) or post-CRT (78%, 21/27 vs. 30%, 3/10; p = 0.017). Patients with detectable ctDNA during CRT had shorter PFS (p = 0.014). Similarly, patients with post-CRT detectable ctDNA had a significantly shorter PFS (p = 0.012) and worse OS (p = 0.004). Moreover, patients with high bTMB levels during CRT had prolonged OS (p = 0.027). In conclusion, ctDNA and bTMB have the potential to predict treatment efficacy and survival in ESCC treated with CRT and immunotherapy.

Integrating bioinformatics and experimental validation to unveil disulfidptosis-related lncRNAs as prognostic biomarker and therapeutic target in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) stands as a prevalent malignancy globally, characterized by significant morbidity and mortality. Despite continuous advancements in the treatment of HCC, the prognosis of patients with this cancer remains unsatisfactory. This study aims at constructing a disulfidoptosis­related long noncoding RNA (lncRNA) signature to probe the prognosis and personalized treatment of patients with HCC. METHODS: The data of patients with HCC were extracted from The Cancer Genome Atlas (TCGA) databases. Univariate, multivariate, and least absolute selection operator Cox regression analyses were performed to build a disulfidptosis-related lncRNAs (DRLs) signature. Kaplan-Meier plots were used to evaluate the prognosis of the patients with HCC. Functional enrichment analysis was used to identify key DRLs-associated signaling pathways. Spearman's rank correlation was used to elucidate the association between the DRLs signature and immune microenvironment. The function of TMCC1-AS1 in HCC was validated in two HCC cell lines (HEP3B and HEPG2). RESULTS: We identified 11 prognostic DRLs from the TCGA dataset, three of which were selected to construct the prognostic signature of DRLs. We found that the survival time of low-risk patients was considerably longer than that of high-risk patients. We further observed that the composition and the function of immune cell subpopulations were significantly different between high- and low-risk groups. Additionally, we identified that sorafenib, 5-Fluorouracil, and doxorubicin displayed better responses in the low-score group than those in the high-score group, based on IC50 values. Finally, we confirmed that inhibition of TMCC1-AS1 impeded the proliferation, migration, and invasion of hepatocellular carcinoma cells. CONCLUSIONS: The DRL signatures have been shown to be a reliable prognostic and treatment response indicator in HCC patients. TMCC1-AS1 showed potential as a novel prognostic biomarker and therapeutic target for HCC.

A 3-Year Survival Update from a Phase 2 Study of Paclitaxel Plus Cisplatin and 5-Fuorouracil Induction Chemotherapy for Locally Advanced Borderline-Resectable Esophageal Squamous Cell Carcinoma: The NEOCRTEC-1601 Clinical Trial.

BACKGROUND: This study updated 3-year analyses to further characterize the impact of docetaxel, cisplatin, and fluorouracil (TPF) chemotherapy followed by surgery. METHODS: This study was a single-center phase 2 clinical trial. Patients with a diagnosis of borderline resectable esophageal squamous cell carcinoma (BR-ESCC) because of the primary tumor or bulky lymph node that potentially invaded adjacent organs were eligible. The treatment started with TPF chemotherapy followed by surgery if the cancer was resectable, or by concurrent chemoradiation if it was unresectable. This updated report presents the 3-year overall survival (OS) and progression-free survival (PFS) rates. RESULTS: Surgery was performed for 27 patients (57.4%), and R0 resection was confirmed in 25 patients (53.2%). Pathologic complete response was confirmed in four patients (8.5%). The median follow-up time for the surviving patients was 44.8 months (range, 3.4-74.6 months). The median OS for all the patients was 41.9 months (95% confidence interval [CI], 18.6-65.3 months), with a median PFS of 38.7 months (95% CI, 23.5-53.9 months). The 3-year survival rate for all the patients was 54.4%. The 3-year survival rate for the R0 patients was 65.4%. CONCLUSION: Long-term follow-up evaluation confirmed that TPF followed by surgery is feasible and promising in terms of survival for BR-ESCC patients. Trial Registration ClinicalTrials.gov identifer: NCT02976909.

Management of metastatic bone disease of melanoma.

One of the most aggressive tumors arising from the skin, mucosa, and uvea is malignant melanoma, which easily metastasizes. Bone tissue is one of the most typical locations for distant metastasis, and around 5%-20% of patients eventually acquired skeletal metastases. For decades, the incidence of bone metastases was higher, bringing greater burden on the family, society, and healthcare system owing to the progress of targeted therapy and immunotherapy, which prolonging the survival time substantially. Moreover, bone metastases result in skeletal-related events, which influence the quality of life, obviously. Appropriate intervention is therefore crucial. To obtain the optimum cost-effectiveness, existing treatment algorithm must be integrated, which is still controversial. We have aimed to throw light on current views concerning the formation, biological and clinical features, and treatment protocol of melanoma bone metastases to guide the decision-making process.

Enzymatic Synthesis of Noncanonical α-Amino Acids Containing γ-Tertiary Alcohols.

Noncanonical amino acids (ncAAs) containing tertiary alcohols are valuable as precursors of natural products and active pharmaceutical ingredients. However, the assembly of such ncAA scaffolds from simple material by C-C bond formation remains a challenging task due to the presence of multiple stereocenters and large steric hindrance. In this study, we present a novel solution to this problem through highly selective enzymatic decarboxylative aldol addition. This method allows for the streamlined assembly of multifunctionalized ncAAs with γ-tertiary alcohols from readily available materials, such as L -aspartatic acid and isatins, vicinal diones and keto esters. The modularity of electrophiles furnished four classes of ncAAs with decent efficiency as well as excellent site and stereocontrol. Computational modeling was employed to gain detailed insight into the catalytic mechanism and to provide a rationale for the observed selectivities. The method offers a single-step approach to producing multifunctionalized ncAAs, which can be directly utilized in peptide synthesis and bioactivity assessment.

Ultralow Lattice Thermal Transport and Considerable Wave-like Phonon Tunneling in Chalcogenide Perovskite BaZrS3.

Chalcogenide perovskites provide a promising avenue for nontoxic, stable thermoelectric materials. Here, the thermal transport and thermoelectric properties of BaZrS3 as a typical orthorhombic perovskite are investigated. An extremely low lattice thermal conductivity κL of 1.84 W/mK at 300 K is revealed for BaZrS3, due to the softening effect of Ba atoms on the lattice and the strong anharmonicity caused by the twisted structure. We demonstrate that coherence contributions to κL, arising from wave-like phonon tunneling, lead to an 18% thermal transport contribution at 300 K. The increasing temperature softens the phonons, thus reducing the group velocity of materials and increasing the scattering phase space. However, it simultaneously reduces the anharmonicity, which is dominant in BaZrS3 and ultimately improves the particle-like thermal transport. In addition, via replacement of the S atom with Se- and Ti-alloying strategy, the ZT value of BaZrS3 is significantly increased from 0.58 to 0.91 at 500 K, making it an important candidate for thermoelectric applications.

Leveraging a disulfidptosis­related lncRNAs signature for predicting the prognosis and immunotherapy of glioma.

BACKGROUND: Gliomas, a prevalent form of primary brain tumors, are linked with a high mortality rate and unfavorable prognoses. Disulfidptosis, an innovative form of programmed cell death, has received scant attention concerning disulfidptosis-related lncRNAs (DRLs). The objective of this investigation was to ascertain a prognostic signature utilizing DRLs to forecast the prognosis and treatment targets of glioma patients. METHODS: RNA-seq data were procured from The Cancer Genome Atlas database. Disulfidptosis-related genes were compiled from prior research. An analysis of multivariate Cox regression and the least absolute selection operator was used to construct a risk model using six DRLs. The risk signature's performance was evaluated via Kaplan-Meier survival curves and receiver operating characteristic curves. Additionally, functional analysis was carried out using GO, KEGG, and single-sample GSEA to investigate the biological functions and immune infiltration. The research also evaluated tumor mutational burden, therapeutic drug sensitivity, and consensus cluster analysis. Reverse transcription quantitative PCR was conducted to validate the expression level of DRLs. RESULTS: A prognostic signature comprising six DRLs was developed to predict the prognosis of glioma patients. High-risk patients had significantly shorter overall survival than low-risk patients. The robustness of the risk model was validated by receiver operating characteristic curves and subgroup survival analysis. Risk model was used independently as a prognostic indicator for the glioma patients. Notably, the low-risk patients displayed a substantial decrease in the immune checkpoints, the proportion of immune cells, ESTIMATE and immune score. IC50 values from the different risk groups allowed us to discern three drugs for the treatment of glioma patients. Lastly, the potential clinical significance of six DRLs was determined. CONCLUSIONS: A novel six DRLs signature was developed to predict prognosis and may provide valuable insights for patients with glioma seeking novel immunotherapy and targeted therapy.

Exploration of the origin of the excellent charge-carrier dynamics in Ruddlesden-Popper oxysulfide perovskite Y2Ti2O5S2.

Although the efficient separation of electron-hole (e-h) pairs is one of the most sought-after electronic characteristics of materials, due to thermally induced atomic motion and other factors, they do not remain separated during the carrier transport process, potentially leading to rapid carrier recombination. Here, we utilized real-time time-dependent density functional theory in combination with nonadiabatic molecular dynamics (NAMD) to explore the separated dynamic transport path within Ruddlesden-Popper oxysulfide perovskite Y2Ti2O5S2 caused by the dielectric layer and phonon frequency difference. The underlying origin of the efficient overall water splitting in Y2Ti2O5S2 is systematically explored. We report the existence of the bi-directional e-h separate-path transport, in which, the electrons transport in the Ti2O5 layer and the holes diffuse in the rock-salt layer. This is in contrast to the conventional e-h separated distribution with a crowded transport channel, as observed in SrTiO3 and hybrid perovskites. Such a unique feature finally results in a long carrier lifetime of 321 ns, larger than that in the SrTiO3 perovskite (160 ns) with only one carrier transport channel. This work provides insights into the carrier transport in lead-free perovskites and yields a novel design strategy for next-generation functionalized optoelectronic devices.

Longitudinal associations of menstrual characteristics with mental health problems among Chinese girls.

Cross-sectional studies indicate that menstrual problems are related to poorer mental health; however, longitudinal studies are limited. This longitudinal study aimed to determine whether baseline menstrual characteristics were risk factors for incident and persistent mental health problems. The study was conducted among Chinese adolescent girls. Menstrual characteristics including menarche, menstrual cycle and menstrual pain were assessed at baseline, whereas mental health problems including PTSD, depression, anxiety, ADHD, insomnia, psychotic-like experiences, non-suicidal self-injury, suicide ideation, suicide plan, and suicide attempt were assessed at baseline (n = 1039) and at the 1-year follow-up (n = 946) by self-administered, structured questionnaires. Multiple logistic regressions were performed to examine whether menstrual characteristics were associated with incident (e.g., PTSD at follow-up but not baseline) and persistent (e.g., PTSD at both time points) mental health problems. The results demonstrated that early menarche was related to persistence of psychotic-like experiences; irregular menstruation was associated with higher rates of incident anxiety and insomnia, and persistent depression, anxiety, ADHD, insomnia, non-suicidal self-injury, suicide ideation, and suicide plan; menstrual pain was associated with elevated rates of incident PTSD and depression, and persistent depression, insomnia, psychotic-like experiences, non-suicidal self-injury, suicidal ideation, suicide plan, and suicide attempt. In conclusion, irregular menstruation and menstrual pain specifically contributed to the development of emotional problems and insomnia, and were associated with maintenance of the most mental health problems in early adolescence. The long-term effects of menstrual problems on mental health need further study.

Exploring key genes associated with neutrophil function and neutrophil extracellular traps in heart failure: a comprehensive analysis of single-cell and bulk sequencing data.

Background: Heart failure (HF) is a complex and heterogeneous manifestation of multiple cardiovascular diseases that usually occurs in the advanced stages of disease progression. The role of neutrophil extracellular traps (NETs) in the pathogenesis of HF remains to be explored. Methods: Bioinformatics analysis was employed to investigate general and single-cell transcriptome sequencing data downloaded from the GEO datasets. Differentially expressed genes (DEGs) associated with NETs in HF patients and healthy controls were identified using transcriptome sequencing datasets and were subsequently subjected to functional enrichment analysis. To identify potential diagnostic biomarkers, the random forest algorithm (RF) and the least absolute shrinkage and selection operator (LASSO) were applied, followed by the construction of receiver operating characteristic (ROC) curves to assess accuracy. Additionally, single-cell transcriptome sequencing data analysis identified key immune cell subpopulations in TAC (transverse aortic constriction) mice potentially involved in NETs regulation. Cell-cell communication analysis and trajectory analysis was then performed on these key cell subpopulations. Results: We identified thirteen differentially expressed genes (DEGs) associated with NET through differential analysis of transcriptome sequencing data from HF (heart failure) samples. Utilizing the Random Forest and Lasso algorithms, along with experimental validation, we successfully pinpointed four diagnostic markers (CXCR2, FCGR3B, VNN3, and FPR2) capable of predicting HF risk. Furthermore, our analysis of intercellular communication, leveraging single-cell sequencing data, highlighted macrophages and T cells as the immune cell subpopulations with the closest interactions with neutrophils. Pseudo-trajectory analysis sheds light on the differentiation states of distinct neutrophil subpopulations. Conclusion: In this study, we conducted an in-depth investigation into the functions of neutrophil subpopulations that infiltrate cardiac tissue in TAC mice. Additionally, we identified four biomarkers (CXCR2, FCGR3B, VNN3, and FPR2) associated with NETs in HF. Our findings enhance the understanding of immunology in HF.

Theoretical Dissection of Cation-Deficient Layered Ruddlesden-Popper Oxysulfide Perovskites with a High-Efficiency Carrier Transport Channel.

The search for lead-free perovskite materials has triggered intensive interest. Here, we study the electronic structures and optical properties of cation-deficient Ruddlesden-Popper oxysulfide perovskites Ln2Ti2O5S2 (Ln = Sc, Y, or La), with a tunable band gap of 1.45-2.1 eV and a small exciton binding energy of ∼0.1 eV, among which Y2Ti2O5S2 has been synthesized experimentally. Sc2Ti2O5S2 possesses the largest light absorbance in the visible region. We further rationalize the light absorption via the transition dipole moment and suggest potential applications of Sc2Ti2O5S2 in solar cells and Y2Ti2O5S2 and La2Ti2O5S2 in water splitting. In addition, this family exhibits small effective masses within the x-y plane and large ones along the z direction. Most importantly, electron gas-like carrier behaviors are observed within the Ti-O bond region, offering a diffusion channel for electron transport. These findings greatly advance our understanding of lead-free perovskites and offer a novel material platform for future optoelectronic devices.