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Abstract This was a multicenter, single-arm, open-label, phase Ib/II study (NCT04255576), aimed to evaluate the efficacy and safety of JMT103 in patients with unresectable or surgically-challenging giant cell tumor of bone (GCTB). JMT103 (2 mg/kg) was administered subcutaneously every four weeks, with loading doses on days 8 and 15. The primary endpoint was the objective tumor response rate (OTR) based on best response, defined as the proportion of patients who achieved elimination of at least 90% of the giant cells or radiologic complete or partial response per the modified Inverse Choi density/size (mICDS) or modified European Organization for Research and Treatment of Cancer (mEORTC) within 12 weeks. Secondary endpoints included objective response rate (ORR) per mICDS and mEORTC, and safety. A total of 139 patients were enrolled, and 135 were analyzed for efficacy. OTR, determined by the independent review committee (IRC) was 93.3% (95% CI 87.7-96.9). Treatment-related adverse events occurred in 90 (64.7%) patients, with hypophosphatemia and hypocalcemia being the most common. No serious treatment-related adverse events were observed. Thus, JMT103 demonstrates potential as a therapeutic option for GCTB.

Abstract Bladder cancer (BC) poses high morbidity and mortality, with urinary exosomal microRNA (miR)‐21 showing potential value in its diagnosis and prognosis, and we probed its specific role. We prospectively selected 116 BC patients and 116 healthy volunteers as the BC and control groups, respectively. BC urinary exosomal miR‐146a‐5p, miR‐93‐5p, miR‐663b, miR‐21, and miR‐4454 relative expression levels were assessed. The correlations between clinical indexes and urinary exosomal miR‐21, prognostic value of miR‐21, and diagnostic value of the five candidate miRNAs, urine cytology, and miRNA joint diagnostic panel for BC and urinary exosomal miR‐21, miR‐4454, and urine cytology for Ta‐T1 and T2‐T4 stage BC were analyzed. Urinary exosomal miR‐146a‐5p, miR‐93‐5p, miR‐663b, miR‐21, and miR‐4454 were highly expressed in BC patients. miR‐146a‐5p, miR‐93‐5p, miR‐663b, miR‐21, miR‐4454, miRNA combined diagnostic panel, and urine cytology had certain diagnostic value for BC, with miR‐21, miR‐4454, and miRNA co‐diagnostic panel showing the highest diagnostic value. Collectively, urinary exosomal miR‐21 was closely related to Tumor‐Node‐Metastasis staging and grading in BC patients. Urinary exosomal miR‐21 had high diagnostic value for BC and Ta‐T1 and T2‐T4 stage BC, and had high predictive value for BC poor prognosis, providing an effective indicator for the occurrence, development, and prognostic assessment of BC.

Objective To observe the effects of a 1 470 nm semiconductor laser on vaporization cutting, coagulation, and thermal injury of ex vivo animal tissues, aiming to explore the feasibility of its application in the treatment of benign prostatic hyperplasia. Methods The experimental group and control group were treated with HANS-D1 and ML-DD01FI 1 470 nm semiconductor laser therapy equipment, respectively. Fresh ex vivo pig bladder tissue was exposed to lasers with the optical fiber placed at distances of 0.5 cm and 1 cm from the tissue for 5 s. The effects of layers at powers of 60, 90, 120, 150, and 160 W on tissue injury were observed. Ex vivo dog prostate and pig kidney tissues were used for vaporization ablation and cutting to observe the effects of lasers at the same power levels on tissue vaporization and cutting thermal injury. Additionally, in coagulation mode, the effects of 30, 40, and 50 W semiconductor lasers on tissue coagulation were observed after irradiating ex vivo pig kidney tissue for 5, 10, and 15 seconds.Results When the optical fiber was placed 1 cm away from the tissue, the 1 470 nm semiconductor lasers did not cause accidental damage to adjacent normal bladder tissue. However, at a distance of 0.5 cm, the 120 W, 150 W, or 160 W lasers caused slight damage to the bladder tissue. In addition, with the increase in output power, the vaporization ablation efficiency of 60-160 W lasers on dog prostate tissue gradually increased, showing a good linear correlation between vaporization volume and total energy consumption (P0.05). Moreover, when performing vaporization cutting on ex vivo pig kidney tissue with a cross-sectional area of 1 cm2, the efficiency of vaporization cutting by the 60-160 W 1 470 nm semiconductor lasers increased with the increase in output power (P0.05). Conclusion The 1 470 nm semiconductor laser shows good vaporization ablation, cutting, and coagulation effect on ex vivo tissues, with a good linear correlation between the effect and the output energy.

Abstract Non-hydraulic root source signaling (nHRS) is a unique positive response to soil drying in the regulation of plant growth and development. However, it is unclear how the nHRS mediates the tradeoff between source and sink at the late growth stages and its adaptive mechanisms in primitive wheat. To address this issue, a root-splitting design was made by inserting solid partition in the middle of the pot culture to induce the occurrence of nHRS using four wheat cultivars (MO1 and MO4, diploid; DM22 and DM31, tetraploid) as materials. Three water treatments were designed as 1) both halves watered (CK), 2) holistic root system watered then droughted (FS), 3) one-half of the root system watered and half droughted (PS). FS and PS were designed to compare the role of the full root system and split root system to induce nHRS. Leaves samples were collected during booting and anthesis to compare the role of nHRS at both growth stages. The data indicated that under PS treatment, ABA concentration was significantly higher than FS and CK, demonstrating the induction of nHRS in split root design and nHRS decreased cytokinin (ZR) levels, particularly in the PS treatment. Soluble sugar and proline accumulation were higher in the anthesis stage as compared to the booting stage. POD activity was higher at anthesis, while CAT was higher at the booting stage. Increased ABA (nHRS) correlated with source-sink relationships and metabolic rate (i.e., leaf) connecting other stress signals. Biomass density showed superior resource acquisition and utilization capabilities in both FS and PS treatment as compared to CK in all plants. Our findings indicate that nHRS-induced alterations in phytohormones and their effect on source-sink relations were allied with the growth stages in primitive wheat.

This study used forestry statistical data and field survey data from 2000 to 2018 to analyze the ecological restoration effect of the returning farmland to forest project in the upper reaches of the Yellow River, considering four perspectives, namely, project construction goals, ecosystem quality, ecosystem service functions, and ecological restoration driving factors. One-way ANOVA and logit regression analysis methods were used for comparison. The results show that the implementation of the Grain for Green Project has reduced the carrying capacity of rural land, effectively curbed the continuous deterioration of the ecological environment, and protected and benefited the forest ecosystem. (1) Initiatives of the return farmland to forest project have achieved the expected goals, and the forest coverage rate has increased significantly from 5.26 % (in 2000) to 15.63 % (in 2019); the proportion of primary, secondary, and tertiary industries related to forestry has reached a reasonable level, and the economic benefits thereof continue to improve. (2) Indicators such as total forest and grass vegetation coverage, vegetation net primary productivity, and forest and grass health index reflect that the functional quality of the regional forest and grass ecosystem is gradually improving. (3) The ecosystem service function of the project region has improved considerably, and the ecological benefits are significant. (4) In terms of the contribution value of the driving forces for this ecological restoration project, they can be ranked as follows: government investment > reducing land carrying capacity > policy of returning farmland to forest > government management > hydrological factors > meteorological factors. (5) After the implementation of the Grain for Green Project, farmers' income has increased significantly, but the changes in livelihood capital income are not synchronized. As the ecological environment in the Grain for Green project areas gradually improved from deterioration, the natural capital and social capital of farmers' livelihood capital decreased significantly, while the physical capital and financial capital increased significantly, with no significant change in human capital. Farmers' satisfaction with the Grain for Green Project is as follows: natural capital has a significant negative impact, while financial capital and social capital have significant positive impacts, and there are no significant changes in physical capital and human capital. Finally, the consistency test results show that the fit is as high as 95 %, and the accuracy exceeds 90 %. Notably, the implementation of the Grain for Green Project has played a pivotal role in ecological restoration and contributed greatly to ecological benefits. These achievements provide a scientific basis and theoretical support for the country to formulate relevant policies for forestry projects, which holds great significance for the country in addressing the contradiction between economic and social development and ecological protection.

Pomelo flowers emit a strong fragrance and give aromatic odors. Volatile compounds from pomelo flowers were analyzed at three developmental stages and in the main organs by molecular sensory science. A total of 134 volatiles including 25 odorants, were analyzed by gas chromatography–mass spectrometry/pulsed flame photometric detector (GC–MS/PFPD) and multidimensional GC–MS/olfactory (MDGC–MS/O). The total volatile content varied among pomelo flowers at different developmental stages (stage-III > stage-II > stage-I) and among different organs of pomelo flowers (petal > pistil > stamen). Linalool was an important odorant with a high OAV, and floral/fruity comprised the predominant aroma profile. Four odorants, ethyl 2-methylbutanoate, linalool, β-myrcene, and 2-butenal, were selected based on variable importance in projection (VIP) values and contributed mainly to the discrimination of pomelo flowers at three different developmental stages. Linalool, β-myrcene, d-limonene, and ethyl hexanoate were potential markers for evaluating flavor differences in pomelo floral organs.

Nowadays, the issue of electromagnetic pollution has become increasingly prominent, underscoring the critical importance of developing high-performance microwave absorbers. This study put forwards the synthesis process of two-dimensional (2D) FeCo/Co8FeS8/C carbon nanosheets, wherein CoSO4 and FeCl3 serve as inorganic salt templates, and dopamine functions as the carbon source. FeCo alloy nanoparticles and Co8FeS8 nanoparticles are loaded on the surface of the carbon layer. 2D structure forms the conductive network, which proves advantages in establishing efficient electronic channels and minimizing conduction losses. The carbon component increases the dielectric constant of the composite and improves its impedance matching, and the FeCo alloy provides a certain ML. The synergistic effect between these components significantly contributes to the exceptional microwave absorption performance of the composites. Accordingly, the minimum reflection loss (RLmin) of FeCo/Co8FeS8/C composite reaches −47.4 dB, its effective absorption bandwidth (EAB) reaches 5.3 GHz. In particular, CST confirms that radar cross-section reduction value of FeCo/Co8FeS8/C composite can reach 20.2 dB m2 in the range of −90°

Background: Retinoblastoma (RB) is a rare primary malignant tumor primarily affecting children. Our study aims to compare the overall survival (OS) between pediatric and adult RB patients and establish a predictive model for adult RB patients' OS to assist clinical decision-making. Methods: This study retrospectively analyzed data from 1938 RB patients in the Surveillance, Epidemiology, and End Results (SEER) database, covering the period from 2000 to 2015. Propensity score matching (PSM) ensured balanced characteristics between pediatric and adult groups. A Cox proportional hazards regression model was used to assess prognostic factors, and selected variables were utilized to construct a predictive survival model. The Nomogram model's performance was evaluated through the C-index, time-dependent ROC curves, calibration curves, and decision curve analysis (DCA). Results: Following PSM, adult RB patients had lower OS compared to pediatric RB patients. Independent prognostic factors for adult RB OS included age, gender, disease stage, radiation therapy, income, and diagnosis confirmation. In the training cohort, the Nomogram achieved a C-index for OS of 0.686 and accurately predicted 2-year, 3-year, and 5-year OS with AUC values of 0.672, 0.680, and 0.660, respectively. The C-index, time-dependent ROC curves, calibration curves, and DCA in both training and validation cohorts confirmed the Nomogram's excellent performance. Conclusion: In this study, adult RB patients have worse OS than pediatric RB patients. Consequently, we constructed a Nomogram to predict the risk for adult RB patients. The Nomogram demonstrated good accuracy and reliability, making it suitable for widespread application in clinical practice to assist healthcare professionals in assessing patients’ prognoses.

Compared with the global situation, it can be found that the cancer incidence in China is close to the world average level, but the mortality rate has difference compared with the global average level. The burden of gynecological cancers in China is increasing, with large differences between urban and rural areas and uneven regional distribution. Therefore, the situation of cancer prevention and control is still challenging. In recent years, new technologies and drugs, such as immune checkpoint inhibitors (ICIs) and antibody-drug conjugate (ADC), have been introduced into clinical practice, bringing new hope for the treatment of gynecological cancers. This article reviewed the major research progress of gynecological cancers in 2023. Among them, in terms of the progress of treatment for cervical cancer, we reviewed the innovation of standard treatment mode and the related progress of post-line treatment for advanced recurrent and metastatic cervical cancer (clinical research such as ENGOT-cx11/GOG-3047/KEYNOTE-A18, KEYNOTE-826). In terms of treatment for ovarian cancer, this review summarized the latest progress of PARP inhibitors, immunotherapy, first-line treatment of newly diagnosed ovarian cancer and treatment of recurrent ovarian cancer (FLAMES, ANITA/ENGOT-Ov41/GEICO 69-O, NRG-GY004, etc.). In terms of treatment for endometrial cancer, this study reviewed the progress in the treatment of locally advanced endometrial cancer (GOG 258, Lunchbox clinical research, etc.) and advanced/recurrent metastatic endometrial cancer (ENGOT-EN6-NSGO/GOG-3031/RUBY research, etc.), and summarized the exploration of back-line targeted immunotherapy (such as KEYNOTE-775, ADAGIO and other clinical studies). This study combed the progress of gynecological tumors in 2023 from the above aspects, aiming at providing reference for clinical practice and clinical research.

Abstract Amino acid availability is monitored by animals to adapt to their nutritional environment. Beyond gustatory receptors and systemic amino acid sensors, enteroendocrine cells (EECs) are believed to directly percept dietary amino acids and secrete regulatory peptides. However, the cellular machinery underlying amino acid-sensing by EECs and how EEC-derived hormones modulate feeding behavior remain elusive. Here, by developing tools to specifically manipulate EECs, we find that Drosophila neuropeptide F (NPF) from mated female EECs inhibits feeding, similar to human PYY. Mechanistically, dietary L-Glutamate acts through the metabotropic glutamate receptor mGluR to decelerate calcium oscillations in EECs, thereby causing reduced NPF secretion via dense-core vesicles. Furthermore, two dopaminergic enteric neurons expressing NPFR perceive EEC-derived NPF and relay an anorexigenic signal to the brain. Thus, our findings provide mechanistic insights into how EECs assess food quality and identify a conserved mode of action that explains how gut NPF/PYY modulates food intake.

Given post-operative aseptic loosening in orthopedic disease treatment, osteointegration occurs at the bone-implant interface as a holistic process, including immunoregulation (e.g., macrophage polarization), angiogenesis and osteogenesis in sequence. In order to achieve early rapid and satisfactory osseointegration, different nano-shaped (nanocone, nanopolyhedron and nanoflower abbr. NC, NP & NF) cerium oxide (CeO2-x) coatings, endowed with “nanozyme-like” activities for multiple free radical elimination and osteoimmunology regulation, were hydrothermally synthesized on titanium alloy (TC4). In vitro cell experiments showed that nano-CeO2-x coated TC4 not only induced polarization of RAW264.7 cells toward M2 phenotype, but also promoted angiogenesis and vascularization of endothelial cells along with differentiation and mineralization of osteogenic precursor cells. Improvements in M2-polarized macrophage, angiogenesis, and bone regeneration were further confirmed in a rat femoral condyle model. Among the above three nano-morphologies, NF exhibited the best osseoinetegration. RNA sequencing and mechanism exploration suggested that the inhibition of PI3K-AKT signaling pathway was essential for immunomodulatory capacity of NF. In conclusion, it provided promising insights into the immunomodulatory exploitation of orthopedic implants.

Objectives Occupational stress is a common complaint in nurses, who perceived more sense of effort-reward imbalance (ERI). Suboptimal health status (SHS) is a state between health and disease. However, the correlation between ERI and SHS is unclear. Therefore, the aim of this study was to examine the prevalence of SHS and ERI and evaluate the relationship between ERI and SHS in clinical nurses by a cross-sectional study. Material and Methods The current cross-sectional study was conducted through an online survey at Dongping People’s Hospital in China. A total of 633 completed surveys were received. Effort-reward imbalance was measured by subscales of the ERI questionnaire. SHS was measured by the Suboptimal Health Status Questionnaire – 25 (SHSQ-25). The relationship between ERI and SHS in nurses was subsequently assessed by Spearman’s correlation coefficient and logistic regression model. Results The mean age of the optimal health status (OHS) group (M±SD 26.3±7.3 years) was younger than the SHS group (M±SD 30.3±6.9 years). The prevalence of SHS was 54.5% (345/633). Female nurses aged ≥30 years, a junior college or university graduate educational level, smokers, and nurses without regular exercise were at a higher risk of SHS. In Spearman’s correlation analysis, ERI reflected by the effort-reward ratio was correlated with SHSQ-25 score (r = 0.662, p < 0.001). In logistic regression, ERI was strongly associated with SHS after potential confounding factors adjusting (OR 27.924, 95% CI 22.845–34.132). Conclusions The prevalence of SHS was significantly high in clinical nurses. Administrators should pay more attention to health status of female nurses aged ≥30 years, with a junior college or bachelor’s degree, smoking, and without regular exercise to reduce the SHS and ERI. Int J Occup Med Environ Health. 2024;37(2):166–75

Abstract Insertion sequences (ISs) exist widely in bacterial genomes, but their roles in the evolution of bacterial antiphage defense remain to be clarified. Here, we report that, under the pressure of phage infection, the IS1096 transposition of Mycobacterium smegmatis into the lsr2 gene can occur at high frequencies, which endows the mutant mycobacterium with a broad‐spectrum antiphage ability. Lsr2 functions as a negative regulator and directly silences expression of a gene island composed of 11 lipid metabolism‐related genes. The complete or partial loss of the gene island leads to a significant decrease of bacteriophage adsorption to the mycobacterium, thus defending against phage infection. Strikingly, a phage that has evolved mutations in two tail‐filament genes can re‐escape from the lsr2 inactivation‐triggered host defense. This study uncovered a new signaling pathway for activating antimycobacteriophage immunity by IS transposition and provided insight into the natural evolution of bacterial antiphage defense.

Background At present, the discovery of new biomarkers is of great significance for the early diagnosis, treatment and prognosis assessment of ovarian cancer. Previous findings indicated that aberrant G-protein-coupled receptor 176 (GPR176) expression might contribute to tumorigenesis and subsequent progression. However, the expression of GPR176 and the molecular mechanisms in ovarian cancer had not been investigated.Methods GPR176 expression was compared with clinicopathological features of ovarian cancer using immunohistochemical and bioinformatics analyses. GPR176-related genes and pathways were analysed using bioinformatics analysis. Additionally, the effects of GPR176 on ovarian cancer cell phenotypes were investigated.Results GPR176 expression positively correlated with elder age, clinicopathological staging, tumour residual status, and unfavourable survival of ovarian cancer, but negatively with purity loss, infiltration of B cells, and CD8+ T cells. Gene Set Enrichment Analysis showed that differential expression of GPR176 was involved in focal adhesion, ECM-receptor interaction, cell adhesion molecules and so on. STRING and Cytoscape were used to determine the top 10 nodes. Kyoto Encyclopaedia of Genes and Genomes analysis indicated that GPR176-related genes were involved in the ECM structural constituent and organisation and so on. GPR176 overexpression promoted the proliferation, anti-apoptosis, anti-pyroptosis, migration and invasion of ovarian cancer cells with overexpression of N-cadherin, Zeb1, Snail, Twist1, and under-expression of gasdermin D, caspase 1, and E-cadherin.Conclusion GPR176 might be involved in the progression of ovarian cancer. It might be used as a biomarker to indicate the aggressive behaviour and poor prognosis of ovarian cancer and a target of genetic therapy.

BackgroundMalignant pleural effusion (MPE) is a common clinical problem that requires cytological and/or histological confirmation obtained by invasive examination to establish a definitive diagnosis. Radiomics is rapidly evolving and can provide a non-invasive tool to identify MPE.ObjectivesWe aimed to develop a model based on radiomic features extracted from unenhanced chest computed tomography (CT) images and investigate its value in predicting MPE.MethodThis retrospective study included patients with pleural effusions between January 2016 and June 2020. All patients underwent a chest CT scanning and medical thoracoscopy after artificial pneumothorax. Cases were divided into a training cohort and a test cohort for modelling and verifying respectively. The Mann-Whitney U test and the least absolute shrinkage and selection operator (LASSO) were applied to determine the optimal features. We built a radiomics model based on support vector machines (SVM) and evaluated its performance using ROC and calibration curve analysis.ResultsTwenty-nine patients with MPE and fifty-two patients with non-MPE were enrolled. A total of 944 radiomic features were quantitatively extracted from each sample and reduced to 14 features for modeling after selection. The AUC of the radiomics model was 0.96 (95% CI: 0.912-0.999) and 0.86 (95% CI: 0.657~1.000) in the training and test cohorts, respectively. The calibration curves for model were in good agreement between predicted and actual data.ConclusionsThe radiomics model based on unenhanced chest CT has good performance for predicting MPE and may provide a powerful tool for doctors in clinical decision-making.

Abstract Artificial micro/nanomotors using active particles hold vast potential in applications such as drug delivery and microfabrication. However, upgrading them to micro/nanorobots capable of performing precise tasks with sophisticated functions remains challenging. Bubble microthruster (BMT) is introduced, a variation of the bubble‐driven microrobot, which focuses the energy from a collapsing microbubble to create an inertial impact on nearby target microparticles. Utilizing ultra‐high‐speed imaging, the microparticle mass and density is determined with sub‐nanogram resolution based on the relaxation time characterizing the microparticle's transient response. Master curves of the BMT method are shown to be dependent on the viscosity of the solution. The BMT, controlled by a gamepad with magnetic‐field guidance, precisely manipulates target microparticles, including bioparticles. Validation involves measuring the polystyrene microparticle mass and hollow glass microsphere density, and assessing the mouse embryo mass densities. The BMT technique presents a promising chip‐free, real‐time, highly maneuverable strategy that integrates bubble microrobot‐based manipulation with precise bioparticle mass and density detection, which can facilitate microscale bioparticle characterizations such as embryo growth monitoring.

BackgroundEvidence from observational studies and clinical trials has associated gut microbiota with infectious diseases. However, the causal relationship between gut microbiota and infectious diseases remains unclear.MethodsWe identified gut microbiota based on phylum, class, order, family, and genus classifications, and obtained infectious disease datasets from the IEU OpenGWAS database. The two-sample Mendelian Randomization (MR) analysis was then performed to determine whether the gut microbiota were causally associated with different infectious diseases. In addition, we performed reverse MR analysis to test for causality.ResultsHerein, we characterized causal relationships between genetic predispositions in the gut microbiota and nine infectious diseases. Eight strong associations were found between genetic predisposition in the gut microbiota and infectious diseases. Specifically, the abundance of class Coriobacteriia, order Coriobacteriales, and family Coriobacteriaceae was found to be positively associated with the risk of lower respiratory tract infections (LRTIs). On the other hand, family Acidaminococcaceae, genus Clostridiumsensustricto1, and class Bacilli were positively associated with the risk of endocarditis, cellulitis, and osteomyelitis, respectively. We also discovered that the abundance of class Lentisphaeria and order Victivallales lowered the risk of sepsis.ConclusionThrough MR analysis, we found that gut microbiota were causally associated with infectious diseases. This finding offers new insights into the microbe-mediated infection mechanisms for further clinical research.