The impact of age and number of mutations on the size of clonal hematopoiesis.

Clonal hematopoiesis (CH) represents the clonal expansion of hematopoietic stem cells and their progeny driven by somatic mutations. Accurate risk assessment of CH is critical for disease prevention and clinical decision-making. The size of CH has been showed to associate with higher disease risk, yet, factors influencing the size of CH are unknown. In addition, the characteristics of CH in long-lived individuals are not well documented. Here, we report an in-depth analysis of CH in longevous (≥90 y old) and common (60~89 y old) elderly groups. Utilizing targeted deep sequencing, we found that the development of CH is closely related to age and the expression of aging biomarkers. The longevous elderly group exhibited a significantly higher incidence of CH and significantly higher frequency of TET2 and ASXL1 mutations, suggesting that certain CH could be beneficial to prolong life. Intriguingly, the size of CH neither correlates significantly to age, in the range of 60 to 110 y old, nor to the expression of aging biomarkers. Instead, we identified a strong correlation between large CH size and the number of mutations per individual. These findings provide a risk assessment biomarker for CH and also suggest that the evolution of the CH is influenced by factor(s) in addition to age.

Panoramic transcriptome analysis and functional screening of long noncoding RNAs in mouse spermatogenesis.

Long noncoding RNAs (lncRNAs) have emerged as diverse functional regulators involved in mammalian development; however, large-scale functional investigation of lncRNAs in mammalian spermatogenesis in vivo is lacking. Here, we delineated the global lncRNA expression landscape in mouse spermatogenesis and identified 968 germ cell signature lncRNAs. By combining bioinformatics and functional screening, we identified three functional lncRNAs (Gm4665, 1700027A15Rik, and 1700052I22Rik) that directly influence spermatogenesis in vivo. Knocking down Gm4665 hampered the development of round spermatids into elongating spermatids and disrupted key spermatogenic gene expression. Mechanistically, lncRNA Gm4665 localized in the nucleus of round spermatids and occupied the genomic regulatory region of important spermatogenic genes including Ip6k1 and Akap3 These findings provide a valuable resource and framework for future functional analysis of lncRNAs in spermatogenesis and their potential roles in other biological processes.

Robotic Versus Laparoscopic Pancreaticoduodenectomy for Pancreatic Cancer: Evaluation and Analysis of Surgical Efficacy.

BACKGROUND: Evidence is limited for the treatment of pancreatic cancer among minimally invasive pancreatoduodenectomy. METHODS: This retrospective analysis evaluated patients who underwent robotic pancreaticoduodenectomy (RPD) or laparoscopic pancreaticoduodenectomy (LPD) from April 2016 to April 2023. Their baseline and perioperative data, including operative time, R0 resection rates, and severe complications rates, were analyzed, and the follow-up data, such as disease-free survival (DFS) and overall survival (OS), were collected. RESULTS: A total of 253 cases of LPD and RPD were performed, and 101 cases with pancreatic cancer were included, of which 54 were LPD and 47 were RPD. The conversion rate (4.3% vs. 29.6%, p = 0.001) and blood loss (400 vs. 575 mL, p < 0.05) were lower in the RPD group. No significant difference was observed between the two groups in terms of operative time, vessel resection rates, and TNM-stage diagnosis; however, R0 resection rates (80.9% vs. 70.4%) and lymph node harvest (24.2 vs. 21.9) had a higher tendency in the RPD group, and postoperative length of stay was shorter in the RPD cohort (11 vs. 13 days). Moreover, improved 1- to 3-years DFS (75.7%, 61.7%, and 36.0% vs. 59.0%, 35.6%, and 21.9%) and OS (94.7%, 84.7%, and 50.8% vs. 84.1%, 63.6%, and 45.5%) was found in the RPD group in comparison with the LPD group. CONCLUSIONS: RPD had advantages in surgical safety and oncological outcomes compared with LPD, but was similar to the latter in perioperative outcomes. Long-term outcomes require further study.

Polymorphism rs2327430 in TCF21 predicts the risk and prognosis of gastric cancer by affecting the binding between TFAP2A and TCF21.

BACKGROUND: Single nuclear polymorphisms (SNPs) have been published to be correlated with multiple diseases. Transcription Factor 21 (TCF21) is a critical transcription factor involved in various types of cancers. However, the association of TCF21 genetic polymorphisms with gastric cancer (GC) susceptibility and prognosis remains unclear. METHODS: A case-control study comprising 890 patients diagnosed with GC and an equal number of cancer-free controls was conducted. After rigorous statistical analysis, molecular experiments were carried out to elucidate the functional significance of the SNPs in the context of GC. RESULTS: TCF21 rs2327430 (OR = 0.78, P = 0.026) provides protection against GC, while rs4896011 (OR = 1.39, P = 0.005) exhibit significant associations with GC risk. Furthermore, patients with the (TC + CC) genotype of rs2327430 demonstrate a relatively favorable prognosis (OR = 0.47, P = 0.012). Mechanistically, chromatin immunoprecipitation assay and luciferase reporter assay revealed that the C allele of rs2327430 disrupts the binding of Transcription Factor AP-2 Alpha (TFAP2A) to the promoter region of TCF21, resulting in increased expression of TCF21 and inhibition of malignant behaviors in GC cells. CONCLUSION: Our findings highlight the significant role of TCF21 SNPs in both the risk and prognosis of GC and provide valuable insights into the underlying molecular mechanisms. Specifically, the disruptive effect of rs2327430 on TCF21 expression and its ability to modulate malignant cell behaviors suggest that rs2327430 may serve as a potential predictive marker for GC risk and prognosis.

Structure-function interrelationships and associated neurotransmitter profiles in drug-naïve benign childhood epilepsy with central-temporal spikes patients.

OBJECTIVES: To explore the interrelationships between structural and functional changes as well as the potential neurotransmitter profile alterations in drug-naïve benign childhood epilepsy with central-temporal spikes (BECTS) patients. METHODS: Structural magnetic resonance imaging (sMRI) and resting-state functional MRI data from 20 drug-naïve BECTS patients and 33 healthy controls (HCs) were acquired. Parallel independent component analysis (P-ICA) was used to identify covarying components among gray matter volume (GMV) maps and fractional amplitude of low-frequency fluctuations (fALFF) maps. Furthermore, we explored the spatial correlations between GMV/fALFF changes derived from P-ICA and neurotransmitter maps in JuSpace toolbox. RESULTS: A significantly positive correlation (p < 0.001) was identified between one structural component (GMV_IC6) and one functional component (fALFF_IC4), which showed significant group differences between drug-naïve BECTS patients and HCs (GMV_IC6: p < 0.01; fALFF_IC4: p < 0.001). GMV_IC6 showed increased GMV in the frontal lobe, temporal lobe, thalamus, and precentral gyrus as well as fALFF_IC4 had enhanced fALFF in the cerebellum in drug-naïve BECTS patients compared to HCs. Moreover, significant correlations between GMV alterations in GMV_IC6 and the serotonin (5HT1a: p < 0.001; 5HT2a: p < 0.001), norepinephrine (NAT: p < 0.001) and glutamate systems (mGluR5: p < 0.001) as well as between fALFF alterations in fALFF_IC4 and the norepinephrine system (NAT: p < 0.001) were detected. CONCLUSION: The current findings suggest co-altered structural/functional components that reflect the correlation of language and motor networks as well as associated with the serotonergic, noradrenergic, and glutamatergic neurotransmitter systems. CLINICAL RELEVANCE STATEMENT: The relationship between anatomical brain structure and intrinsic neural activity was evaluated using a multimodal fusion analysis and neurotransmitters which might provide an important window into the multimodal neural and underlying molecular mechanisms of benign childhood epilepsy with central-temporal spikes. KEY POINTS: Structure-function relationships in drug-naïve benign childhood epilepsy with central-temporal spikes (BECTS) patients were explored. The interrelated structure-function components were found and correlated with the serotonin, norepinephrine, and glutamate systems. Co-altered structural/functional components reflect the correlation of language and motor networks and correlate with the specific neurotransmitter systems.

Endovascular recanalization for pediatric hypertension secondary to total renal artery occlusion.

PURPOSE: To assess the feasibility and efficacy of percutaneous transluminal renal angioplasty (PTRA) for pediatric renovascular hypertension (RVH) secondary to total renal artery occlusion (RAO). METHODS: From 2011 to 2021, 13 pediatric patients with RVH confirmed with 14 occluded renal artery lesions were reviewed. The mean age was11.2 years (range 4 to 16). Nine lesions involved main artery occlusion, while five lesions featured branch occlusion. Blood Pressure Ratio (BPR) was defined as the ratio of the actual BP value to the 95th percentile value adjusted for age, gender, and height. RESULTS: PTRA was performed on nine patients (9/13, 69%). Technical success was achieved in five patients (5/9, 56%), with stent placement in two children (2/9, 22%). During the 12-month follow-up, restenosis was identified in two stent-receiving patients at the 12-month follow-up visit (2/9, 22%). Mean systolic BPR decreased from 1.20 ± 0.07 to 0.96 ± 0.06 (p = 0.003), mean diastolic BPR decreased from 1.19 ± 0.07 to 0.95±0.08 (p = 0.005) and the number of required medications decreased from 3.8 ± 0.8 to 2.4 ± 0.9 (p = 0.052) following PTRA. Subsequent to PTRA, the mean GFR of the occluded kidney improved from 19.5 ± 12.3 mL/ min to 36.3 ± 10.8 mL/ min (p = 0.007) and the mean longitudinal dimension of the affected kidneys significantly increased from 8.2 ± 1.5 cm to 9.2 ± 1.7 cm (p = 0.006). CONCLUSIONS: Endovascular treatment is feasible for pediatric RAO, results in acceptable BP control and preserves renal function.

Enhancing nicotinamide N-methyltransferase bisubstrate inhibitor activity through 7-deazaadenosine and linker modifications.

Nicotinamide N-methyltransferase (NNMT) catalyzes the transfer of a methyl group from S-adenosylmethionine (SAM) to nicotinamide (NAM) and other pyridine-related compounds and is involved in various metabolic processes in the human body. In addition, abnormal expression of NNMT occurs under various pathological conditions such as cancer, diabetes, metabolic disorders, and neurodegenerative diseases, making it a promising drug target worthy of in-depth research. Small-molecule NNMT inhibitors with high potency and selectivity are necessary chemical tools to test biological hypotheses and potential therapies. In this study, we developed a series of highly active NNMT inhibitors by modifying N7 position of adenine. Among them, compound 3-12 (IC50 = 47.9 ± 0.6 nM) exhibited potent inhibitory activity and also had an excellent selectivity profile over a panel of human methyltransferases. We showed that the N7 position of adenine in the NNMT bisubstrate inhibitor was a modifiable site, thus offering insights into the development of NNMT inhibitors.

Synthesis and anti-proliferative effect of novel 4-Aryl-1, 3-Thiazole-TPP conjugates via mitochondrial uncoupling process.

With the advent of mitochondrial targeting moiety such as triphenlyphosphonium cation (TPP+), targeting mitochondria in cancer cells has become a promising strategy for combating tumors. Herein, a series of novel 4-aryl-1,3-thiazole derivatives linked to TPP+ moiety were designed and synthesized. The cytotoxicity against a panel of four cancer cell lines was evaluated by CCK-8 assay. Most of these compounds exhibited moderate to good inhibitory activity over HeLa, PC-3 and HCT-15 cells while MCF-7 cells were less sensitive to most compounds. Among them, compound 12a exhibited a significant anti-proliferative activity against HeLa cells, and prompted for further investigation. Specifically, 12a decreased mitochondrial membrane potential and enhanced levels of reactive oxygen species (ROS). The flow cytometry analysis revealed that compound 12a could induce apoptosis and cell cycle arrest at G0/G1 phase in HeLa cells. In addition, mitochondrial bioenergetics assay revealed that 12a displayed mild mitochondrial uncoupling effect. Taken together, these findings suggest the therapeutic potential of compound 12a as an antitumor agent targeting mitochondria.

Structure of brain grey and white matter in infants with spastic cerebral palsy and periventricular white matter injury.

AIM: To investigate the possible covariation of grey matter volume (GMV) and white matter fractional anisotropy in infants with spastic cerebral palsy (CP) and periventricular white matter injury. METHOD: Thirty-nine infants with spastic CP and 25 typically developing controls underwent structural magnetic resonance imaging and diffusion tensor imaging. Multimodal canonical correlation analysis with joint independent component analysis were used to capture differences in GMV and fractional anisotropy between groups. Correlation analysis was performed between imaging findings and clinical features. RESULTS: Infants with spastic CP showed one joint group-discriminating component (i.e. GMV-fractional anisotropy) associated with regions in the cortico-basal ganglia-thalamo-cortical loop and in the corpus callosum compared to typically developing controls and one modality-specific group-discriminating component (i.e. GMV). Significant negative correlations were found between loadings in certain regions and the motor function score in spastic CP. INTERPRETATION: In infants with spastic CP, covarying GMV-fractional anisotropy and altered GMV in specific regions were implicated in motor dysfunction, which confirmed that simultaneous GMV and fractional anisotropy changes underly motor deficits, but might also extend to sensory, cognitive, or visual dysfunction. These findings also suggest that multimodal fusion analysis allows for a more comprehensive understanding of the relevance between grey and white matter structures and its crucial role in the neuropathological mechanisms of spastic CP.

A prospective study comparing the gasless endoscopic thyroidectomy trans-axillary approach to conventional open thyroidectomy: health and quality of life outcomes.

BACKGROUND: The relationship between different surgical treatments and quality of life remains uncertain for differentiated thyroid carcinoma (DTC). The aim of this study is to compare the gasless endoscopic thyroidectomy trans-axillary approach (ET) and traditional open thyroidectomy (OT) through a prospective cohort study focusing on the rate of the efficacy, and quality of life (QoL). METHODS: This prospective observational longitudinal cohort study enrolled 134 female patients diagnosed with DTC from December 01/2021 to December 31/2022. Multiple scales were applicated to evaluate the differences in quality of life, effectiveness, safety, etc. between the two groups during preoperative and postoperative follow-up periods, including the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, version 3.0 (QOL-C30), Symptom Checklist (SCL-90), Scar Cosmesis Assessment and Rating (SCAR-Q), voice impairment score (VIS), swallowing impairment score (SIS), and neck impairment score (NIS). RESULTS: Among them, 68 accepted ET and 66 patients underwent OT. To enhance comparability between the two groups, the patients enrolled in this study are female. Compared with the OT group, the ET group performed significantly better postoperative physical quality of life, including sound (p = 0.036), swallowing (p < 0.001), and neck function (p = 0.010). The ET group was also associated with significantly better cosmetic satisfaction (p < 0.001), and relatively faster recovery in psychological and emotional situation. CONCLUSIONS: Gasless endoscopic thyroidectomy through an axillary approach leads to good cosmetic and psychological effects, improves postoperative QoL, and could be recommended for rapid postoperative recovery and involvement in daily and social activities.

In vivo detection of the epimer metabolites of sweroside via ultra-performance liquid chromatography time-of-flight mass spectrometry combined with DNPH derivatization.

The metabolites of sweroside were first investigated in vivo with ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOF-MS) in combination with 2,4-dinitrophenylhydrazine derivatization. In addition, the mass detection sensitivity of the major metabolites, epinaucledal and naucledal, via UPLC-TOF-MS was significantly enhanced, and the epimer metabolites were distinctly discovered from plasma following gavage of sweroside in rats. The plasma concentration of epinaucledal and naucledal was quantified via UPLC-TOF-MS in negative mode using erythrocentaurin as the internal standard. The maximum mean plasma concentrations of naucledal and epinaucledal were 75.36 ± 20.10 and 43.52 ± 15.60 ng/ml within 2 h, respectively, following gavage of sweroside at 20 mg/kg. Moreover, the area under the concentration-time curve of naucledal was three times that of epinaucledal. The metabolic process of conversion of sweroside to epinaucledal and naucledal was deduced, and the pharmacological effects of epinaucledal and naucledal will clarify the clinical efficacy of sweroside.

Synthesis, Thermal Stability and Antifungal Evaluation of Two New Pyrrole Esters.

To develop new chemicals that are stable at high temperatures with biological activity, a pyrrole intermediate was firstly synthesized using glucosamine hydrochloride as raw materials through cyclization and oxidation. Further, two novel pyrrole ester derivatives were prepared via Steglich esterification from pyrrole intermediate with vanillin and ethyl maltol, respectively. Nuclear magnetic resonance (1 H-NMR, 13 C NMR), infrared spectroscopy (IR) and high resolution mass spectrometry (HRMS) were used to confirm the target compounds. Thermal behavior of the compounds was investigated by thermogravimetry (TG), differential scanning calorimeter (DSC) and the pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) methods. The plausible pyrolytic mechanism was proposed. Additionally, their biological activities against the pathogens Fusarium graminearum, Fusarium oxysporum, Fusarium moniliforme, Phytophthora nicotianae, and Rhizoctonia solani were assessed. These target compounds showed outstanding antifungal activities and the highest inhibitor rates of 62.50 % and 68.75 % against R. solani with EC50 values of 0.0296 and 0.0200 mg mL-1 , respectively. SDHI protein sequence was molecularly docked to identify the binding mechanisms in the active pocket and examine the interactions between both the molecules and the SDHI protein.

On the Working Mechanisms of Molecules-Based Van der Waals Dielectrics.

Sb2 O3 molecules offer unprecedented opportunities for the integration of a van der Waals (vdW) dielectric and a 2D vdW semiconductor. However, the working mechanisms underlying molecules-based vdW dielectrics remain unclear. Here, the working mechanisms of Sb2 O3 and two Sb2 O3 -like molecules (As2 O3 and Bi2 O3 ) as dielectrics are systematically investigated by combining first-principles calculations and gate leakage current theories. It is revealed that molecules-based vdW dielectrics have a considerable advantage over conventional dielectric materials: defects hardly affect their insulating properties. This shows that it is unnecessary to synthesize high-quality crystals in practical applications, which has been a long-standing challenge for conventional dielectric materials. Further analysis reveals that a large thermionic-emission current renders Sb2 O3 difficult to simultaneously satisfy the requirements of dielectric layers in p-MOS and n-MOS, which hinders its application for complementary metal-oxide-semiconductor (CMOS) devices. Remarkably, it is found that As2 O3 can serve as a dielectric for both p-MOS and n-MOS. This work not only lays a theoretical foundation for the application of molecules-based vdW dielectrics, but also offers an unprecedentedly competitive dielectric (i.e., As2 O3 ) for 2D vdW semiconductors-based CMOS devices, thus having profound implications for future semiconductor industry.

Cu-doped mesoporous SnO2 nanoparticles with rich grain boundaries and oxygen vacancies for photocatalytic CO2-to-CO conversion.

Photocatalytic conversion of carbon dioxide into fuels provides an effective approach to realize carbon resource utilization. However, the photocatalytic efficiency is still relatively low due to the recombination of photogenerated charges. Herein, we have designed Cu-doped SnO2 nanoparticles (Cu-SnO2) using a glucose-involved hydrothermal crystallization method for the photocatalytic reduction of CO2. The rich oxygen vacancies facilitated the separation and transfer of photogenerated charges, and the confined effect of the typical mesoporous structure promoted the adsorption of CO2, especially a high density of grain boundaries (GBs) and the doping of atomic Cu would introduce new active sites to activate CO2 molecules. This elaborately designed catalyst exhibited super and stable photocatalytic conversion activity of CO2-into-CO, with a CO optimal yield of 107 µmol g-1 in 4 h, which was 2.75 times that over pure SnO2. In situ Raman results indicated that the CO2 reduction reaction followed a *COOH pathway on Cu-SnO2. This work provides implications for the construction of a catalyst with rich defects in the field of energy and environmental catalysis.

Identifying the preoperative factors predicting the surgical difficulty of robotic distal pancreatectomy.

BACKGROUND: Few studies have evaluated the preoperative factors predicting the surgical difficulty of robotic distal pancreatectomy (RDP). This study aims to explore such factors and provide guidance on the selection of suitable patients to aid surgeons lacking extensive experience in RDP. METHODS: A retrospective study was conducted on consecutive patients who underwent RDP to identify preoperative factors predicting surgical difficulty. High surgical difficulty was defined by both operation time and intraoperative estimated blood loss exceeding their median, or by conversion to laparotomy. RESULTS: A total of 161 patients were ultimately enrolled, including 51 patients with high levels of surgical difficulty. Multivariate analysis revealed that male sex [OR (95% CI): 4.07 (1.77,9.40), p = 0.001], body mass index (BMI) ≥ 25 kg/m2 OR (95% CI): 2.27 (1.03,5.00), p = 0.042], tumors located at the neck of the pancreas [OR (95% CI): 4.15 (1.49,11.56), p = 0.006] and splenic artery type B [OR (95% CI): 3.28 (1.09,9.91), p = 0.035] were independent risk factors for surgical difficulty. Regarding postoperative complications, high surgical difficulty was associated with the risk of overall complications and pancreatic fistula (grade B/C) (49.0% vs. 22.7%, p < 0.001; 39.2% vs. 19.1%, p = 0.006). CONCLUSION: Male sex, body mass index ≥ 25 kg/m2, tumor located at the neck of the pancreas and splenic artery type B are associated with a high RDP difficulty level. These factors can be used preoperatively to assess the difficulty level of surgery, to help surgeons choose patients suitable for them and ensure surgical safety.

Fault Diagnosis of the Autonomous Driving Perception System Based on Information Fusion.

The reliability of autonomous driving sensing systems impacts the overall safety of the driving system. However, perception system fault diagnosis is currently a weak area of research, with limited attention and solutions. In this paper, we present an information-fusion-based fault-diagnosis method for autonomous driving perception systems. To begin, we built an autonomous driving simulation scenario using PreScan software, which collects information from a single millimeter wave (MMW) radar and a single camera sensor. The photos are then identified and labeled via the convolutional neural network (CNN). Then, we fused the sensory inputs from a single MMW radar sensor and a single camera sensor in space and time and mapped the MMW radar points onto the camera image to obtain the region of interest (ROI). Lastly, we developed a method to use information from a single MMW radar to aid in diagnosing defects in a single camera sensor. As the simulation results show, for missing row/column pixel failure, the deviation typically falls between 34.11% and 99.84%, with a response time of 0.02 s to 1.6 s; for pixel shift faults, the deviation range is between 0.32% and 9.92%, with a response time of 0 s to 0.16 s; for target color loss, faults have a deviation range of 0.26% to 2.88% and a response time of 0 s to 0.05 s. These results prove the technology is effective in detecting sensor faults and issuing real-time fault alerts, providing a basis for designing and developing simpler and more user-friendly autonomous driving systems. Furthermore, this method illustrates the principles and methods of information fusion between camera and MMW radar sensors, establishing the foundation for creating more complicated autonomous driving systems.

Atomically Dispersed Uranium Enables an Unprecedentedly High NH3 Yield Rate.

The low NH3 yield rate is a grand challenge for electrocatalytic N2 reduction to NH3. Herein, we report the first uranium single-atom catalyst (SAC) capable of catalyzing the electrochemical N2 reduction reaction (NRR). The uranium SAC features a low limiting potential (<0.5 V) and near-zero free energy changes for N2 adsorption and NH3 desorption. The integration of these merits enables the uranium SAC to afford an unprecedentedly high NH3 yield rate, 3-4 orders of magnitude higher than that of the Ru(0001) surface, which is widely recognized as an excellent NRR electrocatalyst. Further theoretical analysis reveals that the N2 reduction catalyzed by the uranium SAC is synergistically regulated by the d and f electrons of atomic uranium. This work proposes a promising solution (that is, atomically dispersed uranium) to the daunting challenge associated with the low NH3 yield rate, thus enabling the scalable production of NH3 via electrochemical N2 reduction.

Emission behavior and impact assessment of gaseous volatile compounds in two typical rural domestic waste landfills.

Landfill sites are sources of gaseous volatile compounds. The dumping area (LDA) and leachate storage pool (LSP) of two typical rural domestic waste landfill sites in north China (NLF) and southwest China (SLF) were investigated. We found that 45, 46, 61 and 68 volatile organic compounds (VOC) were present in the air of NLF-LDA, NLF-LSP, SLF-LDA, and SLF-LSP, respectively. And there were 27, 29, 35 and 37 kinds of odorous compounds being detected. Oxygenated compounds (>48.88%), chlorinated compounds (>6.85%), and aromatics (>5.46%), such as organic acid, 1-chlorobutane, and benzene, were the most abundant compounds in both landfills. The SLF-LDA had the highest olfactory effect, with a corresponding total odor activity value of 29,635.39. The ozone-formation potential analysis showed that VOCs emitted from SLF landfills had significantly higher potential for ozone formation than those from NLF landfills, with ozone generation potentials of 166.02, 225.86, 2511.82, and 1615.99 mg/m3 for the NLF-LDA, NLF-LSP, SLF-LDA, and SLF-LSP, respectively. Higher chronic toxicity and cancer risk of VOCs were found in the SLF according to method of Risk Assessment Information System. Based on the sensitivity analysis by the Monte Carlo method, concentrations of benzene, propylene oxide, propylene, trichloroethylene, and N-nitrosodiethylamine, along with exposure duration, daily exposure time, and annual exposure frequency, significantly impacted the risk levels. We provide a scientific basis, which reflects the need for controlling and reducing gaseous pollutants from landfills, particularly rural residential landfills, which may improve rural sanitation.

Changes in T lymphocyte subsets in peripheral blood of patients with middle-advanced cervical cancer before and after nimotuzumab combined with concurrent chemoradiotherapy.

The current study sought to investigate the effect of nimotuzumab combined with concurrent chemoradiotherapy (CCRT + Nim) on T lymphocyte subsets in middle-advanced CC. Firstly, patients with middle-advanced CC were administered CCRT or CCRT + Nim. Next, levels of T lymphocytes in peripheral blood of CC patients pre- or post-treatment and healthy females were determined by flow cytometry. The short-term efficacy was evaluated, and overall survival (OS) and progression-free survival (PFS) of patients were recorded. In addition, the correlation of T lymphocyte subsets post-treatment with OS/PFS was assessed with Pearson analysis. CC patients exhibited decreased total T cells/T helper cells/CD4+/CD8+ ratio and increased T suppressor cells/Tregs in peripheral blood. Meanwhile, CCRT and CCRT + Nim improved T lymphocyte subset imbalance, with CCRT + Nim exhibiting better efficacy. CCRT + Nim exhibited better short-term efficacy and higher PFS than CCRT, with no evident difference in OS. The levels of total T cells/T helper cells/T suppressor cells/Tregs were not significantly-correlated with OS/PFS, and the CD4+/CD8+ ratio was correlated with PFS but not OS. Collectively, CCRT + nimotuzumab ameliorate the imbalance of T lymphocyte subsets in peripheral blood of middle-advanced CC patients, and the CD4+/CD8+ ratio after therapy is correlated with PFS.IMPACT STATEMENTWhat is already known on this subject? The utilisation of Nimotuzumab targeting epidermal growth factor receptor (EGFR) combined with concurrent chemoradiotherapy (CCRT) as an efficient treatment for middle-advanced cervical cancer (CC) has garnered the attention of numerous researchers over the years. T cells represent a major immune cell type in the tumour microenvironment and serve as the basis for maintaining cellular immune functions.What do the results of this study add? Our findings revealed that nimotuzumab combined with CCRT improves the abnormality of T lymphocyte subsets in peripheral blood of patients with middle-advanced CC, such that the CD4+/CD8+ ratio after treatment was significantly correlated with progression-free survival (PFS).What are the implications of these findings for clinical practice and/or further research? CCRT of CC may have a short-term negative impact on the peripheral T-cell immune micro-environment, and the combination of nimotuzumab, cisplatin-based chemotherapy, and radiotherapy enhances the frequency of Tregs in peripheral blood. Our findings illustrated that nimotuzumab combined with CCRT can improve the imbalance of T lymphocyte subsets in peripheral blood of patients with middle-advanced CC. A better understanding of the mechanisms of these therapies will optimise the selection of patients most likely to benefit from treatment, serving as a reference for further research on the relationship between EGFR-specific T cells and clinical benefit in patients treated with nimotuzumab in combination with CCRT.

LASSO and attention-TCN: a concurrent method for indoor particulate matter prediction.

Long time exposure to indoor air pollution environments can increase the risk of cardiovascular and respiratory system damage. Most previous studies focus on outdoor air quality, while few studies on indoor air quality. Current neural network-based methods for indoor air quality prediction ignore the optimization of input variables, process input features serially, and still suffer from loss of information during model training, which may lead to the problems of memory-intensive, time-consuming and low-precision. We present a novel concurrent indoor PM prediction model based on the fusion model of Least Absolute Shrinkage and Selection Operator (LASSO) and an Attention Temporal Convolutional Network (ATCN), together called LATCN. First, a LASSO regression algorithm is used to select features from PM1, PM2.5, PM10 and PM (>10) datasets and environmental factors to optimize the inputs for indoor PM prediction model. Then an Attention Mechanism (AM) is applied to reduce the redundant temporal information to extract key features in inputs. Finally, a TCN is used to forecast indoor particulate concentration in parallel with inputting the extracted features, and it reduces information loss by residual connections. The results show that the main environmental factors affecting indoor PM concentration are the indoor heat index, indoor wind chill, wet bulb temperature and relative humidity. Comparing with Long Short-Term Memory (LSTM) and Gated Recurrent Unit (GRU) approaches, LATCN systematically reduced the prediction error rate (19.7% ~ 28.1% for the NAE, and 16.4% ~ 21.5% for the RMSE) and improved the model running speed (30.4% ~ 81.2%) over these classical sequence prediction models. Our study can inform the active prevention of indoor air pollution, and provides a theoretical basis for indoor environmental standards, while laying the foundations for developing novel air pollution prevention equipment in the future.