pH-responsive and nanoenzyme-loaded artificial nanocells relieved osteomyelitis efficiently by synergistic chemodynamic and cuproptosis therapy.

Osteomyelitis is an osseous infectious disease that primarily affects children and the elderly with high morbidity and recurrence. The conventional treatments of osteomyelitis contain long-term and high-dose systemic antibiotics with debridements, which are not effective and lead to antibiotic resistance with serious side/adverse effects in many cases. Hence, developing novel antibiotic-free interventions against osteomyelitis (especially antibiotic-resistant bacterial infection) is urgent and anticipated. Here, a bone mesenchymal stem cell membrane-constructed nanocell (CFE@CM) was fabricated against osteomyelitis with the characteristics of acid-responsiveness, hydrogen peroxide self-supplying, enhanced chemodynamic therapeutic efficacy, bone marrow targeting and cuproptosis induction. Notably, mRNA sequencing was applied to unveil the underlying biological mechanisms and found that the biological processes related to copper ion binding, oxidative phosphorylation, peptide biosynthesis and metabolism, etc., were disturbed by CFE@CM in bacteria. This work provided an innovative antibiotic-free strategy against osteomyelitis through copper-enhanced Fenton reaction and distinct cuproptosis, promising to complement the current insufficient therapeutic regimen in clinic.

Targeting Dual Immune Checkpoints PD-L1 and HLA-G by Trispecific T Cell Engager for Treating Heterogeneous Lung Cancer.

Immunotherapy targeting immune checkpoints (ICPs), such as programmed death-ligand-1 (PD-L1), is used as a treatment option for advanced or metastatic non-small cell lung cancer (NSCLC). However, overall response rate to anti-PD-L1 treatment is limited due to antigen heterogeneity and the immune-suppressive tumor microenvironment. Human leukocyte antigen-G (HLA-G), an ICP as well as a neoexpressed tumor-associated antigen, is previously demonstrated to be a beneficial target in combination with anti-PD-L1. In this study, a nanobody-based trispecific T cell engager (Nb-TriTE) is developed, capable of simultaneously binding to T cells, macrophages, and cancer cells while redirecting T cells toward tumor cells expressing PD-L1- and/or HLA-G. Nb-TriTE shows broad spectrum anti-tumor effects in vitro by augmenting cytotoxicity mediated by human peripheral blood mononuclear cells (PBMCs). In a humanized immunodeficient murine NSCLC model, Nb-TriTE exhibits superior anti-cancer potency compared to monoclonal antibodies and bispecific T cell engagers. Nb-TriTE, at the dose with pharmacoactivity, does not induce additional enhancement of circulating cytokines secretion from PMBCs. Nb-TriTE effectively prolongs the survival of mice without obvious adverse events. In conclusion, this study introduces an innovative therapeutic approach to address the challenges of immunotherapy and the tumor microenvironment in NSCLC through utilizing the dual ICP-targeting Nb-TriTE.

Effects of antibiotic and disinfectant exposure on the mouse gut microbiome and immune function.

This study explores the effects of disinfectant and antibiotic exposure on gut health, focusing on gut microbiota balance and gut immune function. Our analysis indicates that disinfectants increase the proportion of Gram-positive bacteria, particularly increasing Staphylococcus levels, while antibiotics increase the proportion of Gram-negative bacteria, especially Bacteroides levels. These changes disrupt microbial harmony and affect the gut microbiome's functional capacity. Additionally, our research reveals that both disinfectants and antibiotics reduce colon length and cause mucosal damage. A significant finding is the downregulation of NLRC4, a key immune system regulator in the gut, accompanied by changes in immune factor expression. This interaction between chemical exposure and immune system dysfunction increases susceptibility to inflammatory bowel disease and other gut conditions. Given the importance of disinfectants in disease prevention, this study advocates for a balanced approach to their use, aiming to protect public health while minimizing adverse effects on the gut microbiome and immune function. IMPORTANCE: Disinfectants are extensively employed across various sectors, such as the food sector. Disinfectants are widely used in various sectors, including the food processing industry, animal husbandry, households, and pharmaceuticals. Their extensive application risks environmental contamination, impacting water and soil quality. However, the effect of disinfectant exposure on the gut microbiome and the immune function of animals remains a significant, unresolved issue with profound public health implications. This highlights the need for increased scrutiny and more regulated use of disinfectants to mitigate unintended consequences on gut health and maintain immune system integrity.

Glial swip-10 controls systemic mitochondrial function, oxidative stress, and neuronal viability via copper ion homeostasis.

Cuprous copper [Cu(I)] is an essential cofactor for enzymes that support many fundamental cellular functions including mitochondrial respiration and suppression of oxidative stress. Neurons are particularly reliant on mitochondrial production of ATP, with many neurodegenerative diseases, including Parkinson's disease, associated with diminished mitochondrial function. The gene MBLAC1 encodes a ribonuclease that targets pre-mRNA of replication-dependent histones, proteins recently found in yeast to reduce Cu(II) to Cu(I), and when mutated disrupt ATP production, elevates oxidative stress, and severely impacts cell growth. Whether this process supports neuronal and/or systemic physiology in higher eukaryotes is unknown. Previously, we identified swip-10, the putative Caenorhabditis elegans ortholog of MBLAC1, establishing a role for glial swip-10 in limiting dopamine (DA) neuron excitability and sustaining DA neuron viability. Here, we provide evidence from computational modeling that SWIP-10 protein structure mirrors that of MBLAC1 and locates a loss of function coding mutation at a site expected to disrupt histone RNA hydrolysis. Moreover, we find through genetic, biochemical, and pharmacological studies that deletion of swip-10 in worms negatively impacts systemic Cu(I) levels, leading to deficits in mitochondrial respiration and ATP production, increased oxidative stress, and neurodegeneration. These phenotypes can be offset in swip-10 mutants by the Cu(I) enhancing molecule elesclomol and through glial expression of wildtype swip-10. Together, these studies reveal a glial-expressed pathway that supports systemic mitochondrial function and neuronal health via regulation of Cu(I) homeostasis, a mechanism that may lend itself to therapeutic strategies to treat devastating neurodegenerative diseases.

Effect of time restricted eating versus current practice in dietetics on glycaemic control and cardio-metabolic outcomes in individuals at risk of developing type 2 diabetes: Protocol for a multi-centre, parallel group, non-inferiority, randomised controlled trial.

BACKGROUND: Time restricted eating (TRE) is a dietary strategy that may improve metabolic health. However, no studies have compared TRE with current practice (CP) in dietetics. HYPOTHESIS: TRE will not be inferior to CP to improve glycaemic control in individuals at risk of type 2 diabetes (T2D). METHODS: This parallel group, randomised, non-inferiority, controlled trial randomised 247 participants by site and glycated haemoglobin (HbA1c) into TRE or CP (1:1) for 12 months. Participants were aged 35-70 years, with a body mass index (BMI) >25 but <45 kg/m2, and score ≥15 on the Australian type 2 diabetes risk (AUSDRISK) assessment, without a diagnosis of T2D. Study visits were balanced between groups and all participants received five consultations at 0, 0.5, 1, 2 and 3 months. TRE followed a self-selected 9 h eating window (≥0600 and ≤1900), whereas CP followed Australian dietary guidelines. OUTCOMES: The primary endpoint is the estimate of group mean difference (TRE vs CP) of HbA1c at 4 months in a covariate linear regression adjusting for stratification factors and sex. Secondary efficacy outcomes at 4 and 12 months are changes in fasting glucose, fasting insulin, HOMA-IR and nocturnal glucose by continuous glucose monitor incremental area under the curve and change in HbA1c at 12 months. Other endpoints are exploratory and will not be adjusted for multiplicity. CONCLUSIONS: We will determine whether TRE is an alternate strategy to current practice in dietetics to improve glucose control. TRIAL REGISTRATION: NCT04762251; 21 Feb 2021.

Taraxasterol attenuates zearalenone-induced kidney damage in mice by modulating oxidative stress and endoplasmic reticulum stress.

Taraxasterol is one of the bioactive ingredients from traditional Chinese herb Taraxacum, which exhibits multiple pharmacological activities and protective effects. However, the underlying influence and mechanism of its use against kidney damage caused from zearalenone (ZEA) remain unexplored. The ZEA-induced kidney damage model of mice was established by feeding diets containing ZEA (2 mg/kg), and taraxasterol (5 and 10 mg/kg) was administered by gavage for 28 days. Results demonstrated taraxasterol increased average daily gain (ADG) and average daily feed intake (ADFI), reduced feed-to-gain ratio (F/G) and kidney index of mice induced by ZEA. Taraxasterol alleviated histopathological changes of kidney, reduced ZEA residue and the levels of blood urea nitrogen (BUN), uric acid (UA), and creatinine (CRE). Concurrently, taraxasterol reduced the contents of oxidative stress indicator reactive oxygen species (ROS) and malondialdehyde (MDA), and increased the activities of antioxidant enzymes catalase (CAT), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px). Further, taraxasterol up-regulated the mRNA and protein expression of nuclear factor erythroid-2-related factor 2 (Nrf2), GSH-Px, NAD(P)H quinone oxidoreductase 1 (NQO1), and heme oxygenase-1 (HO-1), and down-regulated the mRNA and protein expression of KELCH like ECH associated protein (Keap1) in Nrf2/Keap1 pathway. Taraxasterol down-regulated the mRNA and protein expression of immunoglobulin binding protein (Bip), C/EBP homologous protein (CHOP), Bcl-2 associated X (Bax), cysteine protease (Caspase)-12, and Caspase-3, and up-regulated B-cell lymphoma 2 (Bcl-2) expression in endoplasmic reticulum stress pathway. This study suggests that taraxasterol attenuates ZEA-induced mouse kidney damage through the modulation of Nrf2/Keapl pathway to play antioxidant role and endoplasmic reticulum stress pathway to enhance anti-apoptotic ability. It will provide a basis for taraxasterol as a potential drug to prevent and treat ZEA-induced kidney damage.

Distinct clinical characteristics and prognosis of pediatric-onset growth hormone-secreting pituitary adenoma (GHPA) patients compared to adult-onset patients.

PURPOSE: To explore the clinical characteristics, treatment, and prognosis of growth hormone-secreting pituitary adenoma (GHPA) patients with pediatric-onset, so as to facilitate clinical management. METHODS: A retrospective cohort study was carried out between 102 pediatric-onset GHPA patients admitted to our hospital from January 2013 to June 2022 and 204 adult-onset GHPA patients who were randomly matched. RESULTS: GHPA with pediatric-onset was predominantly male, associated with higher proportion of genetic syndromes, longer course, and delayed diagnosis. Clinical symptoms of visual field defects and menstrual abnormality were more common. The pediatric-onset group exhibited higher growth hormone (GH) nadir during oral glucose tolerance test (OGTT), higher rates of hyperprolactinemia, larger maximum diameter of adenoma, and higher rates of optic chiasm compression, suprasellar invasion, and pituitary apoplexy. Hypertension, diabetes, and obstructive sleep apnea-hypopnea syndrome (OSAHS) were more common in the adult-onset group. Echocardiography results were similar between the two groups. The pediatric-onset group owned significantly higher treatment scores and proportions of multimodal therapy modality, more surgical complications, and a higher proportion of ki67 ≥ 3%. There was no significant difference in the final cure rate, but male patients with adult-onset had a worse prognosis. The recurrence rate was also similar between two groups. Hypopituitarism was more prevalent in the pediatric-onset group, while the adult-onset group had a higher incidence of other tumors. CONCLUSION: Pediatric-onset GHPA patients exhibit distinct clinical characteristics compared to adult-onset patients. Multimodal therapy modalities could help to achieve a cure rate comparable to that of adult-onset patients.

The clinical impact of serum soluble CD25 levels in children with Langerhans cell histiocytosis.

OBJECTIVE: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm with inflammatory characteristics. This study aims to investigate the correlation between sCD25 levels and clinical characteristics, as well as prognosis, in pediatric LCH. METHODS: Serum sCD25 levels were measured in 370 LCH patients under 18 years old using ELISA assays. The patients were divided into two cohorts based on different treatment regimens. We further assessed the predictive value for the prognosis impact of sCD25 in a test cohort, which was validated in the independent validation cohort. RESULTS: The median serum sCD25 level at diagnosis was 3908 pg/ml (range: 231-44 000pg/ml). sCD25 level was significantly higher in multi-system and risk organ positive (MS RO+) LCH patients compared to single-system(SS) LCH patients (p < 0.001). Patients with elevated sCD25 were more likely to have involvement of risk organs, skin, lung, lymph nodes, or pituitary (all p < 0.05). sCD25 level could predict LCH progression and relapse, with an area under the ROC curve of 60.6 %. The optimal cutoff value was determined at 2921 pg/ml. Patients in the high-sCD25 group had significantly worse progression-free survival compared to those in the low-sCD25 group (p < 0.05). CONCLUSION: Elevated serum sCD25 level at initial diagnosis was associated with high-risk clinical features and worse prognosis. sCD25 level can predict the progression/recurrence of LCH following first-line chemotherapy.

Brachial plexopathy following stereotactic body radiation therapy in apical lung malignancies: A dosimetric pooled analysis of individual patient data.

BACKGROUND AND OBJECTIVES: The aim of this study is to establish dosimetric constraints for the brachial plexus at risk of developing grade ≥ 2 brachial plexopathy in the context of stereotactic body radiation therapy (SBRT). PATIENTS AND METHODS: Individual patient data from 349 patients with 356 apical lung malignancies who underwent SBRT were extracted from 5 articles. The anatomical brachial plexus was delineated following the guidelines provided in the atlases developed by Hall, et al. and Kong, et al.. Patient characteristics, pertinent SBRT dosimetric parameters, and brachial plexopathy grades (according to CTCAE 4.0 or 5.0) were obtained. Normal tissue complication probability (NTCP) models were used to estimate the risk of developing grade ≥ 2 brachial plexopathy through maximum likelihood parameter fitting. RESULTS: The prescription dose/fractionation schedules for SBRT ranged from 27 to 60 Gy in 1 to 8 fractions. During a follow-up period spanning from 6 to 113 months, 22 patients (6.3 %) developed grade ≥2 brachial plexopathy (4.3 % grade 2, 2.0 % grade 3); the median time to symptoms onset after SBRT was 8 months (ranged, 3-54 months). NTCP models estimated a 10 % risk of grade ≥2 brachial plexopathy with an anatomic brachial plexus maximum dose (Dmax) of 20.7 Gy, 34.2 Gy, and 42.7 Gy in one, three, and five fractions, respectively. Similarly, the NTCP model estimates the risks of grade ≥2 brachial plexopathy as 10 % for BED Dmax at 192.3 Gy and EQD2 Dmax at 115.4 Gy with an α/ß ratio of 3, respectively. Symptom persisted after treatment in nearly half of patients diagnosed with grade ≥2 brachial plexopathy (11/22, 50 %). CONCLUSIONS: This study establishes dosimetric constraints ranging from 20.7 to 42.7 Gy across 1-5 fractions, aimed at mitigating the risk of developing grade ≥2 brachial plexopathy following SBRT. These findings provide valuable guidance for future ablative SBRT in apical lung malignancies.

Mechanism of the G/M ratio and zein in enhancing the mechanical and hydrophobic properties of sodium alginate films.

This study developed an edible film based on calcium-crosslinked sodium alginate (SA) using the casting method. The investigation assessed how the α-L-guluronic acid/ß-D-mannuronic acid (G/M ratio) and zein addition influence the film's physicochemical properties. Fourier transform infrared spectroscopy and scanning electron microscopy findings suggest that the G/M ratio modulates the film's physicochemical characteristics by altering SA molecular cross-linking strength and the film's network structure density. At a G/M ratio of 0.85, the film exhibits a more uniform network structure, enhanced moisture resistance, hydrophobicity, and mechanical properties. Zein, evenly dispersed within the film matrix, establishes strong hydrogen bonds and electrostatic interactions with SA, enhancing the film's network structure and boosting its thermophysical, mechanical, and moisture resistance characteristics. The study demonstrates that modifying the G/M ratio and incorporating zein enhances the film's mechanical and hydrophobic properties, broadening its potential applications in food packaging.

Integrated ubiquitomics characterization of hepatocellular carcinomas.

BACKGROUND AND AIMS: Patients with aggressive hepatocellular carcinoma (HCC) have limited therapeutic options. Therefore, a better understanding of HCC pathogenesis is needed to improve treatment. Genomic studies of HCC have improved our understanding of cancer biology. However, the ubiquitomic characteristics of HCC remain poorly understood. We aimed to reveal the ubiquitomic characteristics of HCC and provide clinical feature biomarkers of the aggressive HCC that may be used for diagnosis or therapy in the clinic. APPROACH AND RESULTS: The comprehensive proteomic, phosphoproteomic, and ubiquitomic analyses were performed on tumors and adjacent normal liver tissues from 85 HCC patients. HCCs displayed overexpression of drugable targets CBR1-S151 and CPNE1-S55. COL4A1, LAMC1 and LAMA4 were highly expressed in the DFS poor patients. Phosphoproteomic and ubiquitomic features of HCC revealed crosstalk in metabolism and metastasis. Ubiquitomics predicted diverse prognosis and clarified HCC subtype-specific proteomic signatures. Expression of biomarkers TUBA1A, BHMT2, BHMT, and ACY1 exhibited differential ubiquitination levels and displayed high prognostic risk scores, suggesting that targeting these proteins or their modified forms may be beneficial for future clinical treatment. We validated that TUBA1A K370 deubiquitination drove severe HCC and labeled an aggressive subtype of HCCs. TUBA1A K370 deubiquitination was at least partly attributed to AKT-mediated USP14 activation in HCC. Notably, targeting AKT-USP14-TUBA1A complex promoted TUBA1A degradation and blocked liver tumorigenesis in vivo. CONCLUSIONS: This study expands our knowledge of ubiquitomic signatures, biomarkers, and potential therapeutic targets in HCC.

Organic-Inorganic Hybrid Halide X-ray Scintillator with High Antiwater Stability.

In recent years, low-dimensional organic-inorganic hybrid metal halides have garnered significant attention for optoelectronic applications due to their exceptional photophysical properties, despite their persistent challenge of low stability. Addressing this challenge, our study introduces 1-[5-(trifluoromethyl)pyridin-2-yl]piperazinium (TFPP) as a cation, harvesting a novel one-dimensional hybrid cadmium-based halide semiconductor (TFPP)CdCl4, which exhibits intense blue-light emission upon UV excitation. Additionally, (TFPP)CdCl4 demonstrates a high scintillation performance under X-ray excitation, producing 16600 ± 500 photons MeV-1 and achieving a low detection limit of 0.891 µGyair s-1. Notably, (TFPP)CdCl4 showcases remarkable stability against water, intense light sources, heating, and corrosive environments, positioning it as a promising candidate for optoelectronic applications. Through a blend of experimental techniques and theoretical analyses, including density functional theory calculations, we elucidate the unique photophysical properties and structural stability of (TFPP)CdCl4. These findings significantly contribute to the understanding of low-dimensional hybrid halide semiconductors, offering valuable insights into their potential application in advanced optoelectronic devices and paving the way for further research in this field.

Effect of pseudorabies virus infection on NMDA receptor expression in mice and its role in immunosuppression.

Pseudorabies virus (PRV), an α-herpesvirus, induces immunosuppression and can lead to severe neurological diseases. N-methyl-D-aspartate receptor (NMDAR), an important excitatory nerve receptor in the central nervous system, is linked to various nervous system pathologies. The link between NMDAR and PRV-induced neurological diseases has not been studied. In vivo studies revealed that PRV infection triggers a reduction in hippocampal NMDAR expression, mediated by inflammatory processes. Extensive hippocampal neuronal degeneration was found in mice on the 6th day by hematoxylin-eosin staining, which was strongly correlated with increased NMDAR protein expression. In vitro studies utilizing the CCK-8 assay demonstrated that treatment with an NMDAR antagonist significantly heightened the cytotoxic effects of PRV on T lymphocytes. Notably, NMDAR inhibition did not affect the replication ability of PRV. However, it facilitated the accumulation of pro-inflammatory cytokines in PRV-infected T cells and enhanced the transcription of the CD25 gene through the secretion of interleukin-2 (IL-2), consequently exacerbating immunosuppression. In this study, we found that NMDAR has functional activity in T lymphocytes and is crucial for the inflammatory and immune responses triggered by PRV infection. These discoveries highlight the significant role of NMDAR in PRV-induced neurological disease pathogenesis.

Distinct impulsivity profiles in subtypes of violence among community-dwelling patients with severe mental disorders: a longitudinal study.

BACKGROUND: Although only a few patients with severe mental disorders (SMD) can commit violent behaviour in the community, violent behaviour aggravates the stigma towards patients with SMD. Understanding the subtypes of violent behaviour may be beneficial for preventing violent behaviour among patients with SMD, but it has rarely been studied. METHODS: This longitudinal study investigated 1914 patients with SMD in the community at baseline, and the follow-up period ranged from February 2021 to August 2021. The Barratt Impulsiveness Scale Version-11, the Buss-Perry Aggression Questionnaire, the Impulsive/Premeditated Aggression Scale, the Personality Diagnostic Questionnaire and the MacArthur Community Violence Instrument were used at baseline. The Modified Overt Aggression Scale was used to assess the occurrence of violent behaviour (outcome) during the follow-up period. Cox regression models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Latent class analysis was used to characterise the subtypes of patients with SMD who engaged in violent behaviour at follow-up. RESULTS: We found that 7.2% of patients with SMD presented violent behaviour within six months in the community. Younger age (OR = 0.98, 95% CI = 0.96-1.00, p = 0.016) and no economic source (OR = 1.60, 95% CI = 1.10-2.33, p = 0.014) were risk factors for violent behaviour. Patients with SMD who engaged in violent behaviour could be classified into three subtypes: one class characterised by a history of violence and impulsivity, another class characterised by high levels of aggression and motor impulsivity, and the last class characterised by median cognitive impulsivity. CONCLUSIONS: Socio-demographic factors were risk factors for violent behaviour among patients with SMD, which could eliminate the discrimination toward this group. Impulsivity played a vital role in identifying the three subtypes of patients with SMD who engaged in violent behaviour. These findings may be helpful for the development of a personalised violence risk management plan for patients with SMD who commit violent behaviour in the community.

Distal convoluted tubule-specific disruption of the COP9 signalosome but not its regulatory target Cullin 3 causes tubular injury.

The disease Familial Hyperkalemic Hypertension (FHHt; also known as Gordon Syndrome) is caused by aberrant accumulation of WNK4 activating the NaCl cotransporter (NCC) in the distal convoluted tubule (DCT) of the kidney. Mutations in cullin 3 (CUL3) cause FHHt by disrupting interaction with the deneddylase COP9 signalosome (CSN). Deletion of Cul3 or Jab1 (the catalytically active CSN subunit) along the entire nephron causes a partial FHHt phenotype with activation of the WNK4-SPAK-NCC pathway. However, progressive kidney injury likely prevents hypertension, hyperkalemia, and hyperchloremic metabolic acidosis associated with FHHt. We hypothesized that DCT-specific deletion would more closely model the disease. We utilized Slc12a3-Cre-ERT2 mice to delete Cul3 (DCT-Cul3-/-) or Jab1 (DCT-Jab1-/-) only in DCT and examined the mice after short- and long-term deletion. Short-term, DCT-specific knockout of both Cul3 and Jab1 mice caused elevated WNK4, SPAK, and pNCC abundance. However, neither model demonstrated changes in plasma K+, Cl-, or TCO2, even though no injury was present. Long-term DCT-Jab1-/- mice showed significantly lower NCC and parvalbumin abundance, and higher abundance of kidney injury molecule 1 (KIM-1), a marker of proximal tubule injury. No injury, or reduction in NCC or parvalbumin were observed in long-term DCT-Cul3-/- mice. In summary, the prevention of injury outside the DCT did not lead to a complete FHHt phenotype despite activation of the WNK4-SPAK-NCC pathway, possibly due to insufficient NCC activation. Chronically, only DCT-Jab1-/- mice developed tubule injury and atrophy of the DCT, suggesting a direct JAB1 effect or dysregulation of other cullins as mechanisms for injury.

Bibliometric Analysis of Forensic Human Remains Identification Literature from 1991 to 2022.

OBJECTIVES: To describe the current state of research and future research hotspots through a metrological analysis of the literature in the field of forensic anthropological remains identification research. METHODS: The data retrieved and extracted from the Web of Science Core Collection (WoSCC), the core database of the Web of Science information service platform (hereinafter referred to as "WoS"), was used to analyze the trends and topic changes in research on forensic identification of human remains from 1991 to 2022. Network visualisation of publication trends, countries (regions), institutions, authors and topics related to the identification of remains in forensic anthropology was analysed using python 3.9.2 and Gephi 0.10. RESULTS: A total of 873 papers written in English in the field of forensic anthropological remains identification research were obtained. The journal with the largest number of publications was Forensic Science International (164 articles). The country (region) with the largest number of published papers was China (90 articles). Katholieke Univ Leuven (Netherlands, 21 articles) was the institution with the largest number of publications. Topic analysis revealed that the focus of forensic anthropological remains identification research was sex estimation and age estimation, and the most commonly studied remains were teeth. CONCLUSIONS: The volume of publications in the field of forensic anthropological remains identification research has a distinct phasing. However, the scope of both international and domestic collaborations remains limited. Traditionally, human remains identification has primarily relied on key areas such as the pelvis, skull, and teeth. Looking ahead, future research will likely focus on the more accurate and efficient identification of multiple skeletal remains through the use of machine learning and deep learning techniques.

The influence of open disc repositioning surgery on the internal derangement of the contralateral temporomandibular joint: a prospective study of 96 patients.

OBJECTIVE: To assess the influence of unilateral open disc repositioning surgery (ODRS) of the temporomandibular joint (TMJ) on the internal derangement (ID) of the contralateral joint. METHODS: Patients with bilateral ID of TMJ who underwent unilateral ODRS were enrolled and followed-up for one year. They were divided into two groups based on the contralateral disease: the anterior disc displacement with reduction (ADDWR) and without reduction (ADDWoR). Postoperative evaluation included clinical and MRI evaluation. Indices measured were unilateral intermaxillary distance (UID), visual analogue scale (VAS), disc length (DL), condylar height (CH), and disc-condyle angle (DCA). Paired t tests were used to compare the clinical and MRI indices between different time points. RESULTS: Ninety-six patients were enrolled, including 47 in the ADDWR group and 49 in the ADDWoR group. One-year post-surgery, ODRS led to significant increases in MMO, DL, and CH, and decrease in VAS and DCA on the operated side (P < 0.05). In ADDWR group, UID, DL, and CH increased significantly, and VAS decreased (P < 0.05), with no significant change in DCA (P > 0.05). In ADDWoR group, clinical and MRI variables worsened slightly, except for UID, which remained unchanged (P > 0.05). CONCLUSIONS: ODRS is a promising method for correcting TMJ ID and may improve condition of ADDWR and decrease progress of ADDWoR at the contralateral joint. Preoperative bilateral TMJ evaluation is essential for better outcomes. CLINICAL RELEVANCE: ODRS can effectively treat TMJ ID and produce adaptive changes in the contralateral ID, for which continuous monitoring of the contralateral joint is essential.

Direct RNA sequencing in plants: Practical applications and future perspectives.

The transcriptome serves as a bridge that links genomic variation to phenotypic diversity. A vast number of studies using next-generation RNA sequencing (RNA-seq) over the last 2 decades have emphasized the essential roles of the plant transcriptome in response to developmental and environmental conditions, providing numerous insights into the dynamic changes, evolutionary traces, and elaborate regulation of the plant transcriptome. With substantial improvement in accuracy and throughput, direct RNA sequencing (DRS) has emerged as a new and powerful sequencing platform for precise detection of native and full-length transcripts, overcoming many limitations such as read length and PCR bias that are inherent to short-read RNA-seq. Here, we review recent advances in dissecting the complexity and diversity of plant transcriptomes using DRS as the main technological approach, covering many aspects of RNA metabolism, including novel isoforms, poly(A) tails, and RNA modification, and we propose a comprehensive workflow for processing of plant DRS data. Many challenges to the application of DRS in plants, such as the need for machine learning tools tailored to plant transcriptomes, remain to be overcome, and together we outline future biological questions that can be addressed by DRS, such as allele-specific RNA modification. This technology provides convenient support on which the connection of distinct RNA features is tightly built, sustainably refining our understanding of the biological functions of the plant transcriptome.

Comparative efficacy and safety of anlotinib and topotecan as second-line treatment in small cell lung cancer: a retrospective cohort study.

Background: Small cell lung cancer (SCLC) presents considerable challenges regarding the availability of second-line treatment options, which remain limited. The paucity of effective therapeutic choices at this setting emphasizes the urgent requirement for rigorous research and investigation into novel treatment strategies. To address this clinical gap, the current study aimed to compare the efficacy and safety of anlotinib with the standard second-line treatment, topotecan, in patients with relapsed SCLC. Methods: This retrospective collected data from SCLC patients who received either anlotinib or topotecan as second-line treatment. The primary endpoints were progression-free survival (PFS), while the secondary endpoints included the overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety assessment. Results: The study included 46 SCLC patients, with 20 receiving anlotinib and 26 receiving topotecan as second-line treatment. The anlotinib group showed a significantly longer median PFS compared to the topotecan group [5.6 vs. 2.2 months; hazard ratio (HR) =0.50; 95% confidence interval (CI): 0.27-0.92; P=0.02]. However, there was no statistically significant difference in OS between the two groups (9.1 vs. 7.7 months; HR =0.88; 95% CI: 0.46-1.70; P=0.71). The ORRs were 20.0% and 7.7% (P=0.48), and the DCRs were 70.0% and 23.1% (P=0.007) for the anlotinib and topotecan groups, respectively. Treatment-related adverse events (TRAEs) occurred in 13 patients (65.0%) in the anlotinib group and 20 (76.9%) in the topotecan group (P=0.49). Conclusions: Anlotinib shows the potential to extend PFS and manageable adverse events (AEs) compared to topotecan in the second-line setting for relapsed SCLC.