Thyroid abnormalities identified on CT screening for lung cancer.

PURPOSE: Because incidental thyroid nodules (ITNs) are common extrapulmonary findings in low-dose computed tomography (LDCT) scans for lung cancer screening, we aimed to investigate the frequency of ITNs on LDCT scans separately on baseline and annual repeat scans, the frequency of malignancy among the ITNs, and any association with demographic, clinical, CT characteristics. METHODS: Retrospective case series of all 2309 participants having baseline and annual repeat screening in an Early Lung and Cardiac Action Program (MS-ELCAP) LDCT lung screening program from January 2010 to December 2016 was performed. Frequency of ITNs in baseline and annual repeat rounds were determined. Multivariable regression analysis was performed to identify significant predictors. RESULTS: Dominant ITNs were seen in 2.5 % of 2309 participants on baseline and in 0.15 % of participants among 4792 annual repeat LDCTs. The low incidence of new ITNs suggests slow growth as it would take approximately an average of 16.8 years for a new ITN to be detected on annual rounds of screening. Newly detected ITNs on annual repeat LDCT were all smaller than 15 mm. Regression analysis showed that the increasing of age, coronary artery calcifications score and breast density grade were significant predictors for females having an ITN. No significant predictors were found for ITNs in males. CONCLUSION: ITNs are detected at LDCT however, no malignancy was found. Certain predictors for ITNs in females have been identified including breast density, which may point towards a common causal pathway.

Establishment of novel anti-TIM-3 antibodies interfering with its binding to ligands.

The T cell immunoglobulin and mucin-domain containing-3 (TIM-3) receptor has gained significant attention as a promising target for cancer immunotherapy. The inhibitory effect of T cells by TIM-3 is mediated through the interaction between TIM-3 and its ligands. Ligand-blocking anti-TIM-3 antibodies possess the potential to reactivate antigen-specific T cells and augment anti-tumor immunity. However, the precise ligand-receptor interactions disrupted by the administration of TIM-3 blocking Abs have yet to be fully elucidated. In this study, we have developed a panel of monoclonal antibodies targeting human TIM-3, namely MsT001, MsT065, MsT229, and MsT286. They exhibited high sensitivities (10 pg/mL) and affinities (3.70 × 10-9 to 4.61 × 10-11 M) for TIM-3. The TIM-3 antibodies recognized distinct epitopes, including linear epitopes (MsT001 and MsT065), and a conformational epitope (MsT229 and MsT286). Additionally, the MsT229 and MsT286 displayed reactivity towards cynomolgus TIM-3. The interactions between TIM-3/Gal-9, TIM-3/HMGB-1, and TIM-3/CEACAM-1 disrupt the binding of MsT229 and MsT286, while leaving the binding of MsT001 and MsT065 unaffected. The inhibitory effect on the interaction between Gal-9 and TIM-3 was found to be dose-dependently in the presence of either MsT229 or MsT286. The findings suggested that the involvement of conformational epitopes in TIM-3 is crucial for its interaction with ligands, and we successfully generated novel anti-TIM-3 Abs that exhibit inhibitory potential. In conclusion, our finding offers valuable insights -on the comprehension and targeting of human TIM-3.

The Biological Role of Macrophage in Lung and Its Implications in Lung Cancer Immunotherapy.

The lungs are the largest surface of the body and the most important organ in the respiratory system, which are constantly exposed to the external environment. Tissue Resident Macrophages in lung constitutes the important defense against external pathogens. Macrophages connects the innate and adaptive immune system, and also plays important roles in carcinogenesis and cancer immunotherapy. Lung cancer is the leading cause of cancer-related death worldwide, with an overall five-year survival rate of only 21%. Macrophages that infiltrate or aggregate in lung tumor microenvironment are defined as tumor-associated macrophages (TAMs). TAMs are the main components of immune cells in the lung tumor microenvironment. The differentiation and maturation process of TAMs can be roughly divided into two different types: classical activation pathway produces M1 tumor-associated macrophages, and bypass activation pathway produces M2 tumor-associated macrophages. Studies have found that TAMs are related to tumor invasion, metastasis, and treatment resistance, and show potential as a new target for tumor immunotherapy. Therefore, the biological function of macrophages in lung and the role of TAMs in the occurrence, development, and treatment of lung cancer are discussed in this paper.

Determination of high-risk factors and related spatially influencing variables of heavy metals in groundwater.

Identifying high-risk factors (heavy metals (HMs) and pollution sources) by coupling receptor models and health risk assessment model (HRA) is a novel approach within the field of risk assessment. However, this coupled model ignores the contribution of spatial differentiation to high-risk factors, resulting in the assessment being subjective. Taking Dongting Plain (DTP) as an example, a coupling framework by jointly using the positive matrix factorization model (PMF), HRA, Monte Carlo simulation, and geo-detector was developed, aiming to identify high-risk factors in groundwater, and further explore key environmental variables influencing the spatial heterogeneity of high-risk factors. The results showed that at least 82.86 % of non-carcinogenic risks and 97.41 % of carcinogenic risks were unacceptable for people of all ages, especially infants and children. According to the relationships among HMs, pollution sources, and health risks, As and natural sources were defined as high-risk HMs and sources, respectively. The interactions among Holocene thickness, oxidation-reduction potential, and dissolved organic carbon emerged as the primary drivers of spatial variability in high-risk factors, with their combined explanatory power reaching up to 74%. This proposed framework provides a scientific reference for future studies and a practical reference for environmental authorities in developing effective pollution management measures.

GraphPath: a graph attention model for molecular stratification with interpretability based on the pathway-pathway interaction network.

MOTIVATION: Studying the molecular heterogeneity of cancer is essential for achieving personalized therapy. At the same time, understanding the biological processes that drive cancer development can lead to the identification of valuable therapeutic targets. Therefore, achieving accurate and interpretable clinical predictions requires paramount attention to thoroughly characterizing patients at both the molecular and biological pathway levels. RESULTS: Here, we present GraphPath, a biological knowledge-driven graph neural network with multi-head self-attention mechanism that implements the pathway-pathway interaction network. We train GraphPath to classify the cancer status of patients with prostate cancer based on their multi-omics profiling. Experiment results show that our method outperforms P-NET and other baseline methods. Besides, two external cohorts are used to validate that the model can be generalized to unseen samples with adequate predictive performance. We reduce the dimensionality of latent pathway embeddings and visualize corresponding classes to further demonstrate the optimal performance of the model. Additionally, since GraphPath's predictions are interpretable, we identify target cancer-associated pathways that significantly contribute to the model's predictions. Such a robust and interpretable model has the potential to greatly enhance our understanding of cancer's biological mechanisms and accelerate the development of targeted therapies. AVAILABILITY AND IMPLEMENTATION: https://github.com/amazingma/GraphPath.

The Ribonuclease ZC3H12A is required for self-inflicted DNA breaks after DNA damage in small cell lung cancer cells.

Radiotherapy is the first line treatment for small cell lung cancer (SCLC); However, radio-resistance accompanies with the treatment and hampers the prognosis for SCLC patients. The underlying mechanisms remains elusive. Here we discovered that self-inflicted DNA breaks exist in SCLC cells after radiation. Moreover, using nuclease siRNA screening combined with high-content ArrayScan™ cell analyzer, we identified that Ribonuclease ZC3H12A is required for the self-inflicted DNA breaks after radiation and for SCLC cell survival after DNA damage. ZC3H12A expression was increased in response to DNA damage and when ZC3H12A was knocked down, the DNA repair ability of the cells was impaired, as evidenced by decreased expression of the DNA damage repair protein BRCA1, and increased γH2AX at DNA damage sites. Colony formation assay demonstrates that ZC3H12A knocked down sensitized small cell lung cancer radiotherapy. Therefore, the Ribonuclease ZC3H12A regulates endogenous secondary breaks in small cell lung cancer and affects DNA damage repair. ZC3H12A may act as an important radiotherapy target in small cell lung cancer.

Injectable Double Crosslinked Hydrogel-Polypropylene Composite Mesh for Repairing Full-Thickness Abdominal Wall Defects.

Abdominal wall defects are common clinical diseases, and mesh repair is the standard treatment method. The most commonly used polypropylene (PP) mesh in clinical practice has the advantages of good mechanical properties, stable performance, and effective tissue integration effect. However, direct contact between abdominal viscera and PP mesh can lead to severe abdominal adhesions. To prevent this, the development of a hydrogel-PP composite mesh with anti-adhesive properties may be an effective measure. Herein, biofunctional hydrogel loaded with rosmarinic acid is developed by modifying chitosan and Pluronic F127, which possesses suitable physical and chemical properties and commendable in vitro biocompatibility. In the repair of full-thickness abdominal wall defects in rats, hydrogels are injected onto the surface of PP mesh and applied to intraperitoneal repair. The results indicate that the use of hydrogel-PP composite mesh can alleviate abdominal adhesions resulting from traditional PP mesh implantation by decreasing local inflammatory response, reducing oxidative stress, and regulating the fibrinolytic system. Combined with the tissue integration ability of PP mesh, hydrogel-PP composite mesh has great potential for repairing full-thickness abdominal wall defects.

Biomechanical evaluation of a new intramedullary nail compared with proximal femoral nail antirotation and InterTAN for the management of femoral intertrochanteric fractures.

Purpose: Surgical treatment is the main treatment method for femoral intertrochanteric fractures (FIFs), however, there are lots of implant-related complications after surgery. Our team designed a new intramedullary nail (NIN) to manage such fractures. The purpose of this study was to introduce this new implant and compare it with proximal femoral nail antirotation (PFNA) and InterTAN for treating FIFs. Methods: An AO/OTA 31-A1.3 FIF model was built and three fixation models were created via finite element method, comprising PFNA, InterTAN, and the NIN. Vertical, anteroposterior (A-P) bending, and torsional loads were simulated and applied to the three fixation models. Displacement and stress distribution were monitored. In order to compare PFNA and the NIN deeply, finite element testing was repeated for five times in vertical load case. Results: The finite element analysis (FEA) data indicated that the NIN possessed the most outstanding mechanical properties among the three fixation models. The NIN model had lower maximal stress at implants compared to PFNA and InterTAN models under three load conditions. The trend of maximal stress at bones was similar to that of maximal stress at implants. Besides, the NIN model showed smaller maximal displacement compared with PFNA and InterTAN models under vertical, A-P bending, and torsional load cases. The trend for maximal displacement of fracture surface (MDFS) was almost identical with that of maximal displacement. In addition, there was significant difference between the PFNA and NIN groups in vertical load case (p < 0.05). Conclusion: Compared with PFNA and InterTAN, the NIN displayed the best mechanical properties for managing FIFs, including the lowest von Mises stress at implants and bones, and the smallest maximal displacement and MDFS under vertical, A-P bending, and torsional load cases. Therefore, this study might provide a new choice for patients with FIFs.

A Pluripotential Neutrophil-Mimic Nanovehicle Modulates Immune Microenvironment with Targeted Drug Delivery for Augmented Antitumor Chemotherapy.

The limited therapeutic outcomes and severe systemic toxicity of chemotherapy remain major challenges to the current clinical antitumor therapeutic regimen. Tumor-targeted drug delivery that diminishes the undifferentiated systemic distribution is a practical solution to ameliorating systemic toxicity. However, the tumor adaptive immune microenvironment still poses a great threat that compromises the therapeutic efficacy of chemotherapy by promoting the tolerance of the tumor cells. Herein, a pluripotential neutrophil-mimic nanovehicle (Neutrosome(L)) composed of an activated neutrophil membrane-incorporated liposome is proposed to modulate the immune microenvironment and synergize antitumor chemotherapy. The prominent tumor targeting capability inherited from activated neutrophils and the improved tumor penetration ability of Neutrosome(L) enable considerable drug accumulation in tumor tissues (more than sixfold that of free drug). Importantly, Neutrosome(L) can modulate the immune microenvironment by restricting neutrophil infiltration in tumor tissue, which may be attributed to the neutralization of inflammatory cytokines, thus potentiating antitumor chemotherapy. As a consequence, the treatment of cisplatin-loaded Neutrosome(L) performs prominent tumor suppression effects, reduces systemic drug toxicity, and prolongs the survival period of tumor-bearing mice. The pluripotential neutrophil-mimic nanovehicle proposed in this study can not only enhance the tumor accumulation of chemotherapeutics but also modulate the immune microenvironment, providing a compendious strategy for augmented antitumor chemotherapy.

Bone transport combined with sequential nailing technique for the management of large segmental bone defects after trauma.

Background: Bone transport technique is widely used for the management of large segmental bone defects. However, several reasons may prevent its successful completion, such as poor osteogenesis, docking site nonunion, severe chronic pain and psychological problems. We used sequential nailing technique to solve these problems. The objective of this study was to analyze the clinical effects of our modified technique for the management of large segmental bone defects after trauma. Methods: Twenty-three patients using bone transport combined with sequential nailing technique in our institution from June 2011 to June 2020 were included and analyzed retrospectively. There were 15 males and eight females. The age ranged from 19 to 64 years. There were eight cases suffering from basic medical diseases. The initial injury was open in 14 patients. Seven cases encountered femoral defects and 16 for tibia. The main reasons for sequential nailing technique were docking site nonunion (nine cases), poor osteogenesis (five cases), severe chronic pain (five cases) and psychological problems (four cases). The residual bone defects after removing the external fixator, operation plans, complications and follow-up time were recorded. Bone defect healing was evaluated by Paley score. Results: The mean residual bone defects were (2.9 ± 1.9) cm. The mean time in external fixator was (9.5 ± 3.4) months. The average follow-up time was (23 ± 3) months. With respect to complications, two cases suffered from nonunion again and were treated by bone graft with augmented plate fixation. No infection recurrence was found in these cases. The excellent and good rate of bone defect healing was 91.3%. Conclusion: Bone transport combined with sequential nailing technique could shorten the external fixation time, overcome the inconvenience of the external frame to patients, eliminate chronic pain and be easy for patients to accept. Patients using this modified technique achieved high satisfaction.

Robot Navigation System Assisted PFNA Fixation of Femoral Intertrochanteric Fractures in the Elderly: A Retrospective Clinical Study.

Objective: The incidence of hip fracture in the elderly is increasing. Robot navigation technology has the advantages of minimally invasive and accurate. To explore the difference between the clinical effects of proximal femoral anti-rotation intramedullary nail (PFNA) assisted by robot navigation in the treatment of femoral intertrochanteric fracture and traditional PFNA in the treatment of femoral intertrochanteric fracture in the elderly; analyze the advantages and feasibility of PFNA assisted by robot navigation in the treatment of femoral intertrochanteric fracture in the elderly. Patients and Methods: From February 2021 to October 2022, the elderly (>65 years old) with femoral intertrochanteric fracture underwent surgery in our center. Divided the patients included in the study into 2 groups based on the surgical method. The surgical method of robot group was PFNA fixation assisted by robot navigation, while the surgical method of traditional group was classic PFNA fixation, Baseline data (general condition, Evans classification, time from injury to operation, preoperative hemoglobin) and observation indicators (intraoperative bleeding, operation time, the length of incision for mail nail insertion, postoperative hemoglobin drop, blood transfusion rate and the Harris score of hip joint 1 year after operation) of the two groups were collected to compare whether there were differences between the two groups. Results: There was no statistical difference in baseline data between the two groups (P>0.05). The intraoperative bleeding in the robot group was 68.17±10.66 mL, the intraoperative bleeding in the traditional group was 174±8.11mL (P<0.001). The operation time in the robot group was 68.81 ± 6.89 min, in the traditional group, the operation time was 76.94 ± 8.18 min (P<0.001). The length of incision for mail nail insertion in the robot group was 3.53 ± 0.63 cm, the length of the incision for mail nail insertion in the traditional group was 4.23 ± 0.71 cm (P<0.001). 5 patients (13.9%) in the robot group received blood transfusion treatment, and 13 patients (36.1%) in the traditional group received blood transfusion treatment (P=0.029). The hemoglobin in the robot group decreased by 14.81 ± 3.27 g/l after operation compared with that before operation, while that in the traditional group decreased by 16.69 ± 3.32 g/l (P=0.018). The Harris score of the hip joint of the affected limb in the robot group was excellent in 25 cases, good in 8 cases and poor in 3 cases one year after the operation; In the traditional group, Harris scores were excellent in 18 cases, good in 11 cases and poor in 7 cases (P=0.021). Conclusion: PFNA fixation of femoral intertrochanteric fracture with robot navigation assistance has the advantages of minimally invasive and accurate, shorter operation time, less bleeding and lower blood transfusion rate than traditional surgical methods, and has certain advantages in reducing postoperative complications of elderly patients.

Skin-conformable Flexible and Stretchable Ultrasound Transducer for Wearable Imaging.

Ultrasound imaging offers a non-invasive, radiation-free method for visualizing internal tissues and organs, with deep penetration capabilities. This has established it as a crucial tool for physicians in diagnosing internal tissue pathologies and monitoring human conditions. Nonetheless, conventional ultrasound probes are often characterized by their rigidity and bulkiness. Designing a transducer that can seamlessly adapt to the contours and dynamics of soft, curved human skin presents significant technical hurdles. We present a novel flexible and stretchable ultrasound transducer (FSUT) designed for adaptability to large-curvature surfaces while preserving superior imaging quality. Central to this breakthrough is the innovative use of screen-printed silver nanowires (AgNWs) coupled with a composite elastic substrate, together ensuring robust and stable electrical and mechanical connections. Standard tensile and fatigue tests verify its durability. The mechanical, electrical and acoustic properties of FSUTs are characterised using standard methods, with large tensile strains (≥110%), high flexibility (R ≥1.4 mm) and light weight (≤1.58 g) to meet the needs of wearable devices. Center frequency and -6dB bandwidth are approximately 5.3MHz and 66.47%, respectively. Images of the commercial anechoic cyst phantom yielded an axial and lateral resolution (depths of 10 mm to 70 mm) of approximately 0.31mm and 0.46mm, 0.34mm and 0.84mm respectively. The complex curved surface imaging capabilities of FSUT were tested on agar-gelatin-based breast cyst phantoms under different curvatures. Finally, ultrasound images of the thyroid, brachial and carotid arteries were also obtained from volunteer wearing FSUT.

Genomic profiling and associated B cell lineages delineate the efficacy of neoadjuvant anti-PD-1-based therapy in oesophageal squamous cell carcinoma.

BACKGROUND: Neoadjuvant chemoimmunotherapy has offered novel therapeutic options for patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Depicting the landscape of genomic and immune profiles is critical in predicting therapeutic responses. METHODS: We integrated whole-exome sequencing, single-cell RNA sequencing, and immunofluorescence data of ESCC samples from 24 patients who received neoadjuvant treatment with PD-1 inhibitors plus paclitaxel and platinum-based chemotherapy to identify correlations with therapeutic responses. FINDINGS: An elevation of small insertions and deletions was observed in responders. DNA mismatch repair (MMR) pathway alternations were highly frequent in patients with optimal responses and correlated with tumour infiltrating lymphocytes (TILs). Among the TILs in ESCC, dichotomous developing trajectories of B cells were identified, with one lineage differentiating towards LMO2+ germinal centre B cells and another lineage differentiating towards CD55+ memory B cells. While LMO2+ germinal centre B cells were enriched in responding tumours, CD55+ memory B cells were found to correlate with inferior responses to combination therapy, exhibiting immune-regulating features and impeding the cytotoxicity of CD8+ T cells. The comprehensive evaluation of transcriptomic B cell lineage features was validated to predict responses to immunotherapy in patients with cancer. INTERPRETATION: This comprehensive evaluation of tumour MMR pathway alternations and intra-tumoural B cell features will help to improve the selection and management of patients with ESCC to receive neoadjuvant chemoimmunotherapy. FUNDING: National Science Foundation of China (82373371, 82330053), Eastern Scholar Program at Shanghai Institutions of Higher Learning, National Science and Technology Major Project of China (2023YFA1800204, 2020YFC2008402), and Science and Technology Commission of Shanghai Municipality (22ZR1410700, 20ZR1410800).

Evaluation of tumor microvasculature with 3D ultrasound localization microscopy based on 2D matrix array.

OBJECTIVE: Evaluation of tumor microvascular morphology is of great significance in tumor diagnosis, therapeutic effect prediction, and surgical planning. Recently, two-dimensional ultrasound localization microscopy (2DULM) has demonstrated its superiority in the field of microvascular imaging. However, it suffers from planar dependence and is unintuitive. We propose a novel three-dimensional ultrasound localization microscopy (3DULM) to avoid these limitations. METHODS: We investigated 3DULM based on a 2D array for tumor microvascular imaging. After intravenous injection of contrast agents, all elements of the 2D array transmit and receive signals to ensure a high and stable frame rate. Microbubble signal extraction, filtering, positioning, tracking, and other processing were used to obtain a 3D vascular map, flow velocity, and flow direction. To verify the effectiveness of 3DULM, it was validated on double helix tubes and rabbit VX2 tumors. Cisplatin was used to verify the ability of 3DULM to detect microvascular changes during tumor treatment. RESULTS: In vitro, the sizes measured by 3DULM at 3 mm and 13 mm were 178 [Formula: see text] and 182 [Formula: see text], respectively. In the rabbit tumors, we acquired 9000 volumes to reveal vessels about 30 [Formula: see text] in diameter, which surpasses the diffraction limit of ultrasound in traditional ultrasound imaging, and the results matched with micro-angiography. In addition, there were significant changes in vascular density and curvature between the treatment and control groups. CONCLUSIONS: The effectiveness of 3DULM was verified in vitro and in vivo. Hence, 3DULM may have potential applications in tumor diagnosis, tumor treatment evaluation, surgical protocol guidance, and cardiovascular disease. CLINICAL RELEVANCE STATEMENT: 3D ultrasound localization microscopy is highly sensitive to microvascular changes; thus, it has clinical potential for tumor diagnosis and treatment evaluation. KEY POINTS: • 3D ultrasound localization microscopy is demonstrated on double helix tubes and rabbit VX2 tumors. • 3D ultrasound localization microscopy can reveal vessels about 30 [Formula: see text] in diameter-far smaller than traditional ultrasound. • This form of imaging has potential applications in tumor diagnosis, tumor treatment evaluation, surgical protocol guidance, and cardiovascular disease.

The impact of the HER2-low status on conditional survival in patients with breast cancer.

Introduction: With recent advances in breast cancer (BC) treatment, the disease-free survival (DFS) of patients is increasing and the risk factors for recurrence and metastasis are changing. However, a dynamic approach to assessing the risk of recurrent metastasis in BC is currently lacking. This study aimed to develop a dynamically changing prediction model for recurrent metastases based on conditional survival (CS) analysis. Methods: Clinical and pathological data from patients with BC who underwent surgery at the Affiliated Hospital of Qingdao University between August 2011 and August 2022 were retrospectively analysed. The risk of recurrence and metastasis in patients with varying survival rates was calculated using CS analysis, and a risk prediction model was constructed. Results: A total of 4244 patients were included in this study, with a median follow-up of 83.16 ± 31.59 months. Our findings suggested that the real-time DFS of patients increased over time, and the likelihood of DFS after surgery correlated with the number of years of prior survival. We explored different risk factors for recurrent metastasis in baseline patients, 3-year, and 5-year disease-free survivors, and found that low HER2 was a risk factor for subsequent recurrence in patients with 5-year DFS. Based on this, conditional nomograms were developed. The nomograms showed good predictive ability for recurrence and metastasis in patients with BC. Conclusion: Our study showed that the longer patients with BC remained disease-free, the greater their chances of remaining disease-free again. Predictive models for recurrence and metastasis risk based on CS analysis can help improve the confidence of patients fighting cancer and help doctors personalise treatment and follow-up plans.

Conditional survival in breast cancer With recent advances in breast cancer (BC) treatment, the disease-free survival of patients is increasing and the risk factors for recurrence and metastasis are changing. One of the key risk factor is the human epidermal growth factor receptor 2 (HER2). However, the recent advent of anti-HER2 antibody-drug conjugates (ADC) has challenged the traditional binary classification based on HER2. Patients in the traditional HER2-negative group can now be further classified as HER2-low (ISH-negative with IHC1 or IHC2) or HER2-0 (ISH-negative and IHC-0). Does this categorisation also have some value for the prognosis of BC? To figure this out, we retrospectively analysed the clinical and pathological data of BC patients who underwent surgery at the Affiliated Hospital of Qingdao University between August 2011 and August 2022. The risk of recurrence and metastasis in patients with varying survival rates was calculated using conditional survival analysis, and a risk prediction model was constructed.Our findings suggested that the real-time disease-free survival (DFS) of patients increased over time, and the likelihood of DFS after surgery correlated with the number of years of prior survival. Conditional nomograms were developed for baseline patients, 3-year and 5-year disease-free survivors. The nomograms showed good predictive ability for recurrence and metastasis in patients with BC.

Motility behavior and physiological response mechanisms of aerobic denitrifier, Enterobacter cloacae strain HNR under high salt stress: Insights from individual cells to populations.

The motility behaviors at the individual-cell level and the collective physiological responsive behaviors of aerobic denitrifier, Enterobacter cloacae strain HNR under high salt stress were investigated. The results revealed that as salinity increased, electron transport activity and adenosine triphosphate content decreased from 15.75 µg O2/g/min and 593.51 mM/L to 3.27 µg O2/g/min and 5.34 mM/L, respectively, at 40 g/L, leading to a reduction in the rotation velocity and vibration amplitude of strain HNR. High salinity stress (40 g/L) down-regulated genes involved in ABC transporters (amino acids, sugars, metal ions, and inorganic ions) and activated the biofilm-related motility regulation mechanism in strain HNR, resulting in a further decrease in flagellar motility capacity and an increase in extracellular polymeric substances secretion (4.08 mg/g cell of PS and 40.03 mg/g cell of PN at 40 g/L). These responses facilitated biofilm formation and proved effective in countering elevated salt stress in strain HNR. Moreover, the genetic diversity associated with biofilm-related motility regulation in strain HNR enhanced the adaptability and stability of the strain HNR populations to salinity stress. This study enables a deeper understanding of the response mechanism of aerobic denitrifiers to high salt stress.

Characteristics of dissolved organic matter contribute to Geogenic ammonium enrichment in coastal versus alluvial-lacustrine aquifers.

Elevated concentration levels of geogenic ammonium in groundwater arise from the mineralization of nitrogen-containing natural organic matter in various geological settings worldwide, especially in alluvial-lacustrine and coastal environments. However, the difference in enrichment mechanisms of geogenic ammonium between these two types of aquifers remains poorly understood. To address this knowledge gap, we investigated two representative aquifer systems in central Yangtze (Dongting Lake Plain, DTP) and southern China (Pearl River Delta, PRD) with contrasting geogenic ammonium contents. The use of optical and molecular characterization of DOM combined with hydrochemistry and stable carbon isotopes has revealed differences in DOM between the two types of aquifer systems and revealed contrasting controls of DOM on ammonium enrichment. The results indicated higher humification and degradation of DOM in DTP groundwater, characterized by abundant highly unsaturated compounds. The degradation of DOM and nitrogen-containing DOM was dominated by highly unsaturated compounds and CHO+N molecular formulas in highly unsaturated compounds, respectively. In contrast, the DOM in PRD groundwater was more biogenic, less degraded, and contained more aliphatic compounds in addition to highly unsaturated compounds. The degradation of DOM and nitrogen-containing DOM was dominated by aliphatic compounds and polyphenols and CHO+N molecular formulas in highly unsaturated compounds and polyphenols, respectively. As DOM degraded, the ammonium production efficiency of DOM decreased, contributing to lower ammonium concentrations in DTP groundwater. In addition, the CHO+N(SP) molecular formulas were mainly of microbial-derived and gradually accumulated with DOM degradation. In this study, we conducted the first comprehensive investigation into the patterns of groundwater ammonium enrichment based on DOM differences in various geological settings.

A feasibility study of robot-assisted percutaneous reduction and fixation technique for treating posterolateral depression tibial plateau fractures.

Posterolateral (PL)-depression fractures of the tibial plateau are difficult to manage. The aim of this study was: (1) to present our experience with a novel technique of robot-assisted percutaneous reduction and fixation and (2) to compare it with the traditional percutaneous screw osteosynthesis (PSO) technique for the treatment of PL-depression tibial plateau fractures. The clinical data of patients with PL-depression tibial plateau fractures treated by robot-assisted percutaneous reduction and fixation technique and traditional PSO technique from January 2017 to January 2021 were retrospectively analyzed. Among them, there were 18 cases in the robot-assisted group (RA group) and 23 cases in the PSO group. All fractures were unilateral, closed and fresh PL-depression fractures of the tibial plateau. Patients in the RA group were treated by robot assisted reduction and minimally invasive absorbable screw fixation. The PSO group was treated by closed reduction and percutaneous absorbable screw osteosynthesis. The incision length, operation time, intraoperative blood loss, fluoroscopic times, inpatient time, weight training time and postoperative complications of the two groups were statistically analyzed. The Rasmussen radiological score was used to assess the reduction quality after operation while the Rasmussen functional score was used to evaluate knee joint functions at one year postoperatively. All patients were followed for at least one year. There was no significant difference in demographic information between the two groups (p > 0.05). Compared with the PSO group, the RA group showed less fluoroscopic times and better Rasmussen radiological and functional scores (p < 0.05). Besides, there was no significant difference in the incidence of postoperative complications between the two groups (p > 0.05). The novel robot-assisted percutaneous reduction and fixation technique had the characteristics of less radiation, accurate reduction and fixation. It could accelerate the rehabilitation of patients with PL-depression fractures of the tibial plateau and enable patients to obtain good joint functions.

The expanding Pandora's toolbox of CD8+T cell: from transcriptional control to metabolic firing.

CD8+ T cells are the executor in adaptive immune response, especially in anti-tumor immunity. They are the subset immune cells that are of high plasticity and multifunction. Their development, differentiation, activation and metabolism are delicately regulated by multiple factors. Stimuli from the internal and external environment could remodel CD8+ T cells, and correspondingly they will also make adjustments to the microenvironmental changes. Here we describe the most updated progresses in CD8+ T biology from transcriptional regulation to metabolism mechanisms, and also their interactions with the microenvironment, especially in cancer and immunotherapy. The expanding landscape of CD8+ T cell biology and discovery of potential targets to regulate CD8+ T cells will provide new viewpoints for clinical immunotherapy.

Gastrodin inhibits prostate cancer proliferation by targeting canonical Wnt/ß-catenin signaling pathway.

Prostate cancer is an epithelial malignant tumor occurring in the prostate and is the most common malignant tumor in the male genitourinary system. In recent years, the incidence of prostate cancer in China has shown a trend of sudden increase. The search for new and effective drugs to treat prostate cancer is therefore extremely important.The canonical Wnt/ß-catenin signaling pathway has been shown to be involved in the regulation of tumor proliferation, migration and differentiation. Activation of the canonical Wnt/ß-Catenin signaling pathway in the prostate has oncogenic effects. Drugs targeting the canonical Wnt/ß-catenin signaling pathway have great potential in the treatment of prostate cancer. In this study, we found that Gastrodin could significantly inhibit the proliferation of prostate cancer cell line PC3 and DU145. Oral administration Gastrodin could significantly inhibit the tumor growth of PC3 cells subcutaneously injected. Gastrodin has an inhibitory effect on canonical Wnt/ß-Catenin signaling pathway in Prostate cancer, and this inhibitory effect can be abolished by Wnt/ß-Catenin agonist LiCl. These findings raise the possibility that Gastrodin can be used in the treatment of Prostate cancer by targeting canonical Wnt/ß-Catenin signaling pathway.