Minimal residual disease profiling predicts pathological complete response in esophageal squamous cell carcinoma.

Accurate presurgical prediction of pathological complete response (pCR) can guide treatment decisions, potentially avoiding unnecessary surgeries and improving the quality of life for cancer patients. We developed a minimal residual disease (MRD) profiling approach with enhanced sensitivity and specificity for detecting minimal tumor DNA from cell-free DNA (cfDNA). The approach was validated in two independent esophageal squamous cell carcinoma (ESCC) cohorts. In a cohort undergoing neoadjuvant, surgical, and adjuvant therapy (NAT cohort), presurgical MRD status precisely predicted pCR. All MRD-negative cases (10/10) were confirmed as pCR by pathological evaluation on the resected tissues. In contrast, MRD-positive cases included all the 27 non-pCR cases and only one pCR case (10/10 vs 1/28, P < 0.0001, Fisher's exact test). In a definitive radiotherapy cohort (dRT cohort), post-dRT MRD status was closely correlated with patient prognosis. All MRD-negative patients (25/25) remained progression-free during the follow-up period, while 23 of the 26 MRD-positive patients experienced disease progression (25/25 vs 3/26, P < 0.0001, Fisher's exact test; progression-free survival, P < 0.0001, log-rank test). The MRD profiling approach effectively predicted the ESCC patients who would achieve pCR with surgery and those likely to remain progression-free without surgery. This suggests that the cancer cells in these MRD-negative patients have been effectively eliminated and they could be suitable candidates for a watch-and-wait strategy, potentially avoiding unnecessary surgery.

Enhancing Zinc Electrode Stability Through Pre-Desolvation and Accelerated Charge Transfer via a Polyimide Interface for Zinc-Ion Batteries.

Aqueous zinc-based energy storage devices possess superior safety, cost-effectiveness, and high energy density; however, dendritic growth and side reactions on the zinc electrode curtail their widespread applications. In this study, these issues are mitigated by introducing a polyimide (PI) nanofabric interfacial layer onto the zinc substrate. Simulations reveal that the PI nanofabric promotes a pre-desolvation process, effectively desolvating hydrated zinc ions from Zn(H2O)6 2+ to Zn(H2O)4 2+ before approaching the zinc surface. The exposed zinc ion in Zn(H2O)4 2+ provides an accelerated charge transfer process and reduces the activation energy for zinc deposition from 40 to 21 kJ mol-1. The PI nanofabric also acts as a protective barrier, reducing side reactions at the electrode. As a result, the PI-Zn symmetric cell exhibits remarkable cycling stability over 1200 h, maintaining a dendrite-free morphology and minimal byproduct formation. Moreover, the cell exhibits high stability and low voltage hysteresis even under high current densities (20 mA cm-2, 10 mAh cm-2) thanks to the 3D porous structure of PI nanofabric. When integrated into full cells, the PI-Zn||AC hybrid zinc-ion capacitor and PI-Zn||MnVOH@SWCNT zinc-ion battery achieve impressive lifespans of 15000 and 600 cycles with outstanding capacitance retention. This approach paves a novel avenue for high-performance zinc metal electrodes.

Preoperative chemoradiotherapy in older patients with rectal cancer guided by comprehensive geriatric assessment within a multidisciplinary team-a multicenter phase II trial.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of preoperative concurrent chemoradiotherapy (preCRT) for locally advanced rectal cancer in older people who were classified as "fit" by comprehensive geriatric assessment (CGA). METHODS: A single-arm, multicenter, phase II trial was designed. Patients were eligible for this study if they were aged 70 years or above and met the standards of "fit" (SIOG1) as evaluated by CGA and of the locally advanced risk category. The primary endpoint was 2-year disease-free survival (DFS). Patients were scheduled to receive preCRT (50 Gy) with raltitrexed (3 mg/m2 on days 1 and 22). RESULTS: One hundred and nine patients were evaluated by CGA, of whom eighty-six, eleven and twelve were classified into the fit, intermediate and frail category. Sixty-eight fit patients with a median age of 74 years were enrolled. Sixty-four patients (94.1%) finished radiotherapy without dose reduction. Fifty-four (79.3%) patients finished the prescribed raltitrexed therapy as planned. Serious toxicity (grade 3 or above) was observed in twenty-four patients (35.3%), and fourteen patients (20.6%) experienced non-hematological side effects. Within a median follow-up time of 36.0 months (range: 5.9-63.1 months), the 2-year overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) rates were 89.6% (95% CI: 82.3-96.9), 92.4% (95% CI: 85.9-98.9) and 75.6% (95% CI: 65.2-86.0), respectively. Forty-eight patients (70.6%) underwent surgery (R0 resection 95.8%, R1 resection 4.2%), the corresponding R0 resection rate among the patients with positive mesorectal fascia status was 76.6% (36/47). CONCLUSION: This phase II trial suggests that preCRT is efficient with tolerable toxicities in older rectal cancer patients who were evaluated as fit based on CGA. TRIAL REGISTRATION: The registration number on ClinicalTrials.gov was NCT02992886 (14/12/2016).

Vascular clips for preventing lymphocele and symptomatic lymphocele in patients with gynecologic malignancies after laparoscopic pelvic lymphadenectomy.

STUDY OBJECTIVE: To evaluate the effectiveness of using vascular clips to seal targeted lymphatics in gynecological malignancies for the prevention of postoperative pelvic lymphocele and symptomatic lymphocele after laparoscopic pelvic lymphadenectomy. DESIGN: Retrospective analysis. SETTING: Single-center academic hospital. PATIENTS: In total, 217 patients with gynecological malignancies were included. INTERVENTIONS: Patients were classified into two groups: group 1 (vascular clips were used to seal the targeted lymphatics) and group 2 (electrothermal instruments were used to seal the targeted lymphatics). The patients were followed up 4-6 weeks after surgery to evaluate the incidence of lymphoceles by ultrasound or CT. Symptomatic lymphoceles are defined as those that cause infection, deep vein thrombosis with or without swelling of the extremities, edema (swelling) of the extremities or perineum, hydronephrosis and/or moderate to severe pain. MEASUREMENT AND MAIN RESULTS: One hundred and thirteen patients were enrolled in group 1, and 104 patients were enrolled in group 2. Lymphoceles were observed in 46 (21.2%) patients. Fewer lymphoceles occurred in group 1 than in group 2 [8 (7.1%) vs. 38 (36.5%), p < 0.001]. The percentage of significantly sized lymphoceles was lower in group 1 than that in group 2 [4 (3.5%) vs. 30 (28.8%), p < 0.001]. Symptomatic lymphoceles occurred in 18 patients (8.3%), and only one (1.0%) occurred in group 1, while 17 (16.3%) occurred in group 2 (p < 0.001). A multivariate analysis revealed that vascular clips were the only independent factor for preventing lymphocele (OR = 7.65, 95% CI = [3.30, 17.13], p < 0.001) and symptomatic lymphocele (OR = 22.03, 95% CI = [2.84, 170.63], p = 0.003). CONCLUSIONS: The results indicate that the use of vascular clips may be useful for the prevention of the development of lymphocele and symptomatic lymphocele secondary to pelvic lymphadenectomy performed via laparoscopy.

Integrating porphyrin-based nanoporous organic polymers with electrochemical aptasensors for ultratrace detection of kanamycin.

The synthesis and characterization of two new porphyrin-based porous organic polymers (POPs) via Sonogashira cross-coupling reaction and leverage the two obtained POPs is reported for the fabrication of electrochemical aptasensors to detect kanamycin at an ultratrace level. The resultant electrochemical aptasensor demonstrates a high linear relationship with the logarithmic value of kanamycin concentration in the range 5 × 10-5-5 µg/L with the limit of detection of 17.6 pg/L or 36.3 fM. During the analysis of real samples from milk and river, a relative standard deviation of less than 4.39%, and good recovery values in the range 97.0-105% were obtained.

[Clinical observational study on the treatment of oligozoospermia with Shizi Sanhua decoction combined with Nuoyu].

OBJECTIVE: To study the clinical therapeutic effect as well as drug effectiveness and safety of Shizi Sanhua decoction combined with Nuoyu in the treatment of oligozoospermia in men. METHODS: 102 patients with oligozoospermia diagnosed at Longhua Hospital of Shanghai University of Traditional Chinese Medicine from February 2022 to March 2023 were selected and randomly divided into 3 groups. The treatment group was treated with Shizi Sanhua Decoction + Nuoyu; the traditional Chinese medicine group was treated with Shizi Sanhua Decoction; and the Nuoyu nutrient group was treated with Nuoyu nutrient. A review assessment and record were made after one course of treatment (3 months). RESULTS: A total of 102 patients completed the trial due to the treatment process. There were 34 cases in each of the traditional Chinese medicine group, the Nuoyu nutrient group, and the treatment group. Clinical efficacy: total effective rate of 52.94% in the traditional Chinese medicine group; 58.82% in the Nuoyu nutrient group; 82.35% in the treatment group. The clinical efficacy of the treatment group was better than that of the traditional Chinese medicine group and the Nuoyu nutrient group (P<0.05), which was statistically significant. Semen routine: the treatment group was better than the traditional Chinese medicine group and Nuoyu nutrient group in improving the total number of sperm and sperm concentration. CONCLUSION: The semen concentration and forward sperm count of patients with oligozoospermia treated with Shizi Sanhua Decoction combined with Nuoyu improved more significantly, and the clinical efficacy was remarkable. And the clinical efficacy is not affected by age and disease duration. It can be popularized and applied as a treatment for oligozoospermia.

Bayesian hypernetwork collaborates with time-difference evolutional network for temporal knowledge prediction.

A Temporal Knowledge Graph (TKG) is a sequence of Knowledge Graphs (KGs) attached with time information, in which each KG contains the facts that co-occur at the same timestamp. Temporal knowledge prediction (TKP) aims to predict future events given observed historical KGs in TKGs, which is essential for many applications to provide intelligent analysis services. However, most existing TKP methods focus on entity and relation prediction tasks but ignore the importance of time prediction tasks. Furthermore, there is uncertainty in time prediction, and it is difficult for prediction models to model it completely. In this work, we propose a collaboration framework with Bayesian Hypernetwork and Time-Difference Evolutional Network (BH-TDEN) to address these problems. First, we begin with the time prediction task, and we present a Bayesian hypernetwork to model the uncertainty of events time. For the input of Bayesian hypernetwork, we design a novel time-difference evolutional network to obtain the entities and relations embedding. Specifically, we propose an auto-regressive time gate parameterized by the time difference of adjacent KGs in entity and relation encoder to learn the time-sensitive TKG embedding, which not only learns the relationship between the given time information and TKG embedding but also provides more expressive TKG embedding for Bayesian hypernetwork to accurately predict the time of future events. Furthermore, we also present a novel relation updating mechanism that employs the neighbor relations of the subject corresponding to the current relation to learn more adaptive relation embedding. Extensive experiments demonstrate that the proposed method obtains considerable time prediction and link prediction performance on four TKG benchmark datasets.

Efficacy of tibial cortex transverse transport in treating diabetic foot ulcer and its effect on serum omentin-1 and irisin levels.

OBJECTIVE: Diabetic foot ulcer (DFU) is a common and debilitating complication of diabetes that is associated with an increased risk of lower-limb amputation and a reduced life expectancy. Tibial cortex transverse transport (TTT) has become a newly alternative surgical method to facilitate ulcer healing and prevent lower limb amputation. Herein, we investigated the efficacy of TTT in treating DFU and changes of serum omentin-1 and irisin levels. METHODS: This study prospectively recruited 52 consecutive patients with DFU who were treated with TTT. The follow-up was performed weekly during the first 12 weeks postoperatively and every 3 months until 1 year after TTT. The serum levels of vascular endothelial growth factor (VEGF), omentin-1, and irisin in DFU patients undergoing TTT were determined by ELISA methods on the preoperative 1st day, postoperative 2nd week and 4th week. RESULTS: The wound healing rate was 92.3% (48/52) at the 1-year follow-up. The visual analog scale (VAS) pain scores of patients showed a significant reduction at the 4th week after TTT (p < 0.001). The dorsal foot skin temperature, ankle brachial index, and dorsal foot blood flow of patients were significantly increased at the 4th week after TTT (p < 0.001). Results of ELISA methods showed the serum levels of VEGF, omentin-1, and irisin on the 2nd week and 4th week after TTT were notably elevated compared to the levels determined on the preoperative 1st day (p < 0.001). The serum levels of VEGF, omentin-1, and irisin on the 4th week after TTT were also significantly higher than the levels determined on the 2nd week after TTT (p < 0.001). CONCLUSION: TTT could promote the wound healing and reduce the risk of lower limb amputation, demonstrating promising clinical benefits in the treatment of DFU. Increased expressions of serum proangiogenic factors including VEGF, omentin-1, and irisin were noted in the early stage after TTT, which may provide a new mechanism of TTT promoting wound heal.

Causal link between docosahexaenoic acid and osteoporosis: A 2-sample Mendelian randomization study.

To explore the causal relationship between docosahexaenoic acid and osteoporosis. Possible causal links were investigated using a 2-sample Mendelian randomization study. Its genetic correlation was estimated using chained disequilibrium regression. Sensitivity tests were also performed. There was a causal association between docosahexaenoic acid and osteoporosis, and docosahexaenoic acid was a risk factor for osteoporosis (P = .033, odds ratio [95% CI] = 1.099 [1.008-1.198]). For every 1 standard deviation increase in docosahexaenoic acid lev, the risk of developing osteoporosis increased by 9.900%. The genetic correlation between docosahexaenoic acid (h2_Z = 5.260, P = 1.430e-7), osteoporosis (h2_Z = 8.780, P = 1.160e-98), and genes was significant, but there was a weak genetic correlation between docosahexaenoic acid and osteoporosis (rg = -0.040, P = 1.630e-18). Blood levels of docosahexaenoic acid are causally linked to osteoporosis and are a risk factor for osteoporosis. However, this causal link is not brought about by genetic variation. The exact mechanism needs to be explored further.

Biomechanical and clinical outcomes of 3D-printed versus modular hemipelvic prostheses for limb-salvage reconstruction following periacetabular tumor resection: a mid-term retrospective cohort study.

BACKGROUND: Debates persist over optimal pelvic girdle reconstruction after acetabular tumor resection, with surgeons grappling between modular and 3D-printed hemipelvic endoprostheses. We hypothesize superior outcomes with 3D-printed versions, yet scarce comparative research exists. This study fills the gap, examining biomechanics and clinical results retrospectively. METHODS: From February 2017 to June 2021, we retrospectively assessed 32 patients undergoing en bloc resection for malignant periacetabular tumors at a single institution. PRIMARY OUTCOME: limb function. SECONDARY OUTCOMES: implant precision, hip joint rotation center restoration, prosthesis-bone osteointegration, and complications. Biomechanical characteristics were evaluated through finite element analysis on pelvic defect models. RESULTS: In the 3D-printed group, stress distribution mirrored a normal pelvis, contrasting the modular group with elevated overall stress, unstable transitions, and higher stress peaks. The 3D-printed group exhibited superior functional scores (MSTS: 24.3 ± 1.8 vs. 21.8 ± 2.0, p < 0.05; HHS: 79.8 ± 5.2 vs. 75.3 ± 3.5, p < 0.05). Prosthetic-bone interface osteointegration, measured by T-SMART, favored 3D-printed prostheses, but surgery time (426.2 ± 67.0 vs. 301.7 ± 48.6 min, p < 0.05) and blood loss (2121.1 ± 686.8 vs. 1600.0 ± 505.0 ml, p < 0.05) were higher. CONCLUSIONS: The 3D-printed hemipelvic endoprosthesis offers precise pelvic ring defect matching, superior stress transmission, and function compared to modular endoprostheses. However, complexity, fabrication expertise, and challenging surgical implantation result in prolonged operation times and increased blood loss. A nuanced consideration of functional outcomes, complexity, and patient conditions is crucial for informed treatment decisions. LEVEL OF EVIDENCE: Level III, therapeutic study (Retrospective comparative study).

A Quadrivalent mRNA Immunization Elicits Potent Immune Responses against Multiple Orthopoxviral Antigens and Neutralization of Monkeypox Virus in Rodent Models.

The global outbreak of the 2022 monkeypox virus infection of humans and the 2023 documentation of a more virulent monkeypox in the Democratic Republic of the Congo raised public health concerns about the threat of human-to-human transmission of zoonotic diseases. Currently available vaccines may not be sufficient to contain outbreaks of a more transmissible and pathogenic orthopoxvirus. Development of a safe, effective, and scalable vaccine against orthopoxviruses to stockpile for future emergencies is imminent. In this study, we have developed an mRNA vaccine candidate, ALAB-LNP, expressing four vaccinia viral antigens A27, L1, A33, and B5 in tandem in one molecule, and evaluated the vaccine immunogenicity in rodent models. Immunization of animals with the candidate mRNA vaccine induced a potent cellular immune response and long-lasting antigen-specific binding antibody and neutralizing antibody responses against vaccinia virus. Strikingly, the sera from the vaccine-immunized mice cross-reacted with all four homologous antigens of multiple orthopoxviruses and neutralized monkeypox virus in vitro, holding promise for this mRNA vaccine candidate to be used for protection of humans from the infection of monkeypox and other orthopoxvirus.

Investigating the causal impact of polycystic ovary syndrome on gestational diabetes mellitus: a two-sample Mendelian randomization study.

Introduction: Determining the causal relationship between polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) holds significant implications for GDM prevention and treatment. Despite numerous observational studies suggesting an association between PCOS and GDM, it remains unclear whether a definitive causal relationship exists between these two conditions and which specific features of PCOS contribute to increased incidence of GDM. Methods: The causal relationship between polycystic ovary syndrome (PCOS), its characteristic indices, and gestational diabetes mellitus (GDM) was investigated using a two-sample Mendelian randomization study based on publicly available statistics from genome-wide association studies (GWAS). The inverse-variance weighted method was employed as the primary analytical approach to examine the association between PCOS, its characteristic indices, and GDM. MR Egger intercept was used to assess pleiotropy, while Q values and their corresponding P values were utilized to evaluate heterogeneity. It is important to note that this study adopts a two-sample MR design where PCOS and its characteristic indices are considered as exposures, while GDM is treated as an outcome. Results: The study results indicate that there is no causal relationship between PCOS and GDM (all methods P > 0.05, 95% CI of OR values passed 1). The IVW OR value was 1.007 with a 95% CI of 0.906 to 1.119 and a P value of 0.904. Moreover, the MR Egger Q value was 8.141 with a P value of 0.701, while the IVW Q value was also 8.141 with a P value of 0.774, indicating no significant heterogeneity. Additionally, the MR Egger intercept was 0.0004, which was close to zero with a P value of 0.988, suggesting no pleiotropy. However, the study did find a causal relationship between several other factors such as testosterone, high-density lipoprotein, sex hormone-binding globulin, body mass index, waist-hip ratio, apolipoprotein A-I, number of children, diabetes illnesses of mother, father and siblings, hemoglobin A1c, fasting insulin, fasting blood glucose, years of schooling, and GDM based on the IVW method. Conclusion: We observed no association between genetically predicted PCOS and the risk of GDM, implying that PCOS itself does not confer an increased susceptibility to GDM. The presence of other PCOS-related factors such as testosterone, high-density lipoprotein, and sex hormone-binding globulin may elucidate the link between PCOS and GDM. Based on these findings, efforts aimed at preventing GDM in individuals with PCOS should prioritize those exhibiting high-risk features rather than encompassing all women with PCOS.

Research situation, hot spots, and global trends of melasma therapy: Bibliometric insights and visual analysis from 2000 to 2023.

BACKGROUND: Melasma is a prevalent pigmented disease, yet its pathogenesis remains unclear, posing challenges for effective treatment. Bibliometric analysis, a novel approach to literature research, offers the opportunity to evaluate research trends through qualitative and quantitative methods. This study utilizes bibliometric methods to analyze the existing literature on melasma treatment, examining influential publications, institutions, countries, and authors through statistical analysis. METHODS: In order to retrieve manuscripts related to the topic of melasma treatment, we conducted a search using the search formula: (TS = (melasma or Chloasma or "mask of pregnancy")) AND TS = (treatment or therapy). We searched through the Web of Science Core Collection database, covering publications from 2000 to 2023. VOSviewer, CiteSpace and the Bibliometric online site (https://bibliometric.com/app) were used to conduct this bibliometric analysis. Our analysis focused on various factors including publications, authors co-authorship, institutions, countries, citation analysis, keywords co-occurrence, references co-citation and journal co-citation. RESULTS: A total of 943 articles and 200 reviews were published between 2000 and 2023, accumulating a total of 8628 citations. The average number of citations per item was 18.85, and the average number of citations per year was 292.69. The most prolific author, Sungeun Chang, contributed a total of 9 articles. Cario University emerged as the top research institution. The United States led in terms of article publications with a count of 276. In the past 5 years, the research trends in this field have primarily focused on tranexamic acid and epidermal melasma, as indicated by the burst analysis of publications and keywords. CONCLUSIONS: The United States continues to lead in terms of institutions and research output. The current emphasis is on the meticulous implementation of tranexamic acid and laser therapy. It is crucial to foster enhanced collaboration among countries, institutions, and authors to facilitate improved research.

Characteristics of advanced anaerobic digestion sludge-based biochar and its application for sewage sludge conditioning.

The utilization of sludge-based biochar, characterized by abundant pore structures, proves advantageous in enhancing sludge dewatering performance. In this study, advanced anaerobic digestion sludge underwent pyrolysis to produce biochar, subsequently employed for sludge conditioning. Results revealed that biochar, obtained at 800 °C, exhibited the highest specific surface area (105.3 m2/g) and pore volume (0.17 cm3/g). As the pyrolysis temperature increased, the sludge's functional groups tended to aromatize. When used to condition sludge, particularly at a 20 % (dry solid) dosage, biochar significantly reduced sludge capillary suction time and floc size. The addition of biochar enhanced the conditioning effect of cationic polyacrylamide by absorbing extracellular polymeric substances, creating water molecule channels, and forming skeletons for sludge flocs. These findings introduce a novel approach to sludge reuse and provide valuable data supporting the use of biochar as a sludge conditioner.

Unsupervised Bidirectional Contrastive Reconstruction and Adaptive Fine-Grained Channel Attention Networks for image dehazing.

Recently, Unsupervised algorithms has achieved remarkable performance in image dehazing. However, the CycleGAN framework can lead to confusion in generator learning due to inconsistent data distributions, and the DisentGAN framework lacks effective constraints on generated images, resulting in the loss of image content details and color distortion. Moreover, Squeeze and Excitation channel attention employs only fully connected layers to capture global information, lacking interaction with local information, resulting in inaccurate feature weight allocation for image dehazing. To solve the above problems, in this paper, we propose an Unsupervised Bidirectional Contrastive Reconstruction and Adaptive Fine-Grained Channel Attention Networks (UBRFC-Net). Specifically, an Unsupervised Bidirectional Contrastive Reconstruction Framework (BCRF) is proposed, aiming to establish bidirectional contrastive reconstruction constraints, not only to avoid the generator learning confusion in CycleGAN but also to enhance the constraint capability for clear images and the reconstruction ability of the unsupervised dehazing network. Furthermore, an Adaptive Fine-Grained Channel Attention (FCA) is developed to utilize the correlation matrix to capture the correlation between global and local information at various granularities promotes interaction between them, achieving more efficient feature weight assignment. Experimental results on challenging benchmark datasets demonstrate the superiority of our UBRFC-Net over state-of-the-art unsupervised image dehazing methods. This study successfully introduces an enhanced unsupervised image dehazing approach, addressing limitations of existing methods and achieving superior dehazing results. The source code is available at https://github.com/Lose-Code/UBRFC-Net.

DDE: Deep Dynamic Epidemiological Modeling for Infectious Illness Development Forecasting in Multi-level Geographic Entities.

Understanding and addressing the dynamics of infectious diseases, such as coronavirus disease 2019, are essential for effectively managing the current situation and developing intervention strategies. Epidemiologists commonly use mathematical models, known as epidemiological equations (EE), to simulate disease spread. However, accurately estimating the parameters of these models can be challenging due to factors like variations in social distancing policies and intervention strategies. In this study, we propose a novel method called deep dynamic epidemiological modeling (DDE) to address these challenges. The DDE method combines the strengths of EE with the capabilities of deep neural networks to improve the accuracy of fitting real-world data. In DDE, we apply neural ordinary differential equations to solve variant-specific equations, ensuring a more precise fit for disease progression in different geographic regions. In the experiment, we tested the performance of the DDE method and other state-of-the-art methods using real-world data from five diverse geographic entities: the USA, Colombia, South Africa, Wuhan in China, and Piedmont in Italy. Compared to the state-of-the-art method, DDE significantly improved accuracy, with an average fitting Pearson coefficient exceeding 0.97 across the five geographic entities. In summary, the DDE method enhances the accuracy of parameter fitting in epidemiological models and provides a foundation for constructing simpler models adaptable to different geographic areas.

[Effect of Thermal Hydrolysis Pretreatment Time on Microbial Community Structure in Sludge Anaerobic Digestion System].

To evaluate the effect of thermal hydrolysis pretreatment time on the sludge anaerobic digestion system of wastewater treatment plants (WWTPs) in Daxing district, Beijing, the structure and diversity of microbial communities in primary sludge and an activated sludge anaerobic digestion system with different thermal hydrolysis pretreatment times (15 min, 30 min, and 45 min) were analyzed using Illumina MiSeq high-throughput sequencing. The results showed that the dominant groups of digested sludge were mainly distributed in Firmicutes, Cloacimonadota, Chloroflexi, and Synergistota, with W5 being the most common genus. The sum of relative abundance of the dominant phylum was greater than 60%, and W5 accounted for 20.8%-54.5%, showing a high abundance of a few dominant species. During the anaerobic digestion of thermo-hydrolyzed sludge, the relative abundance of acetogenic methanogens decreased due to high levels of volatile fatty acids (VFAs) and ammonia nitrogen (NH4+-N) concentrations, which suggested that the hydrogenophilic methanogenic pathway was more than that of the acetogenic methanogenic pathway. Correlation analysis showed that the soluble protein and pH of thermo-hydrolyzed sludge, NH4+-N of digested sludge, and thermal hydrolysis pretreatment time were the four main environmental factors affecting microbial community structure, and NH4+-N of digested sludge had the largest negative correlation with methanogens. The thermal hydrolysis pretreatment time was negatively correlated with both the Chao index and Shannon index, so longer thermal hydrolysis pretreatment time was not conducive to microbial flora during anaerobic digestion.

Diagnostic model for hepatocellular carcinoma using small extracellular vesicle-propagated miRNA signatures.

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Small extracellular vesicles (sEVs) are bilayer lipid membrane vesicles containing RNA that exhibit promising diagnostic and prognostic potential as cancer biomarkers. Aims: To establish a miRNA panel from peripheral blood for use as a noninvasive biomarker for the diagnosis of HCC. Methods: sEVs obtained from plasma were profiled using high-throughput sequencing. The identified differential miRNA expression patterns were subsequently validated using quantitative real-time polymerase chain reaction analysis. Results: The random forest method identified ten distinct miRNAs distinguishing HCC plasma from non-HCC plasma. During validation, miR-140-3p (p = 0.0001) and miR-3200-3p (p = 0.0017) exhibited significant downregulation. Enrichment analysis uncovered a notable correlation between the target genes of these miRNAs and cancer development. Utilizing logistic regression, we developed a diagnostic model incorporating these validated miRNAs. Receiver operating characteristic (ROC) curve analysis revealed an area under the curve (AUC) of 0.951, with a sensitivity of 90.1% and specificity of 87.8%. Conclusion: These aberrantly expressed miRNAs delivered by sEVs potentially contribute to HCC pathology and may serve as diagnostic biomarkers for HCC.

Projecting the response of ecological risk to land use/land cover change in ecologically fragile regions.

Anthropogenic activities have dramatically altered land use/land cover (LULC), leading to ecosystem service (ES) degradation and further ecological risks. Ecological risks are particularly serious in ecologically fragile regions because trade-offs between economic development and ecological protection are prominent. Thus, ways in which to assess the response of ecological risks to LULC change under each development scenario in ecologically fragile regions remain challenging. In this study, future LUCC and its impact on ESs under four development scenarios in 2040 in western Jilin Province were predicted using a patch-generating land use simulation model and the Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) model. Ecological risk was assessed based on future LUCC possibilities, and potential ES degradation and potential drivers of ecological risks were explored using a geographic detector. The results showed that the cropland development scenario (CDS) would experience large-scale urbanization and cropland expansion. Carbon storage (CS), habitat quality (HQ), and water purification (WP) degraded the most under the CDS, and grain yield (GY) and water yield (WY) degraded the most under the ecological protection scenario (EPS). The LUCC probability under the CDS (14.37 %) was the highest, while the LUCC probability under the comprehensive development scenario (CPDS) (8.68 %) was the lowest. The risk of WP degradation was greatest under the CDS, but the risk of soil retention (SR) degradation was greatest under the natural development scenario (NDS), EPS, and CPDS. Ecological risk coverage was the largest (98.04 %), and ecological risks were the highest (0.21) under the CDS, while those under the EPS were the opposite. Distance to roads and population density had a higher impact on ecological risks than other drivers. Further attention should be given to the ecological networks and pattern establishment in urbanized regions. This study will contribute to risk prevention and sustainable urban and agricultural development.

CDK4/6 Inhibitors Impede Chemoresistance and Inhibit Tumor Growth of Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is characterized by rapid development of chemoresistance and poor outcomes. Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) are widely used in breast cancer and other cancer types. However, the molecular mechanisms of CDK4/6 in SCLC chemoresistance remain poorly understood. Here, Rb1flox/flox, Trp53flox/flox, Ptenflox/flox (RTP) and Rb1flox/flox, Trp53flox/flox, MycLSL/LSL (RPM) spontaneous SCLC mouse models, SCLC cell line-derived xenograft (CDX) models, and SCLC patient-derived xenograft (PDX) models are established to reveal the potential effects of CDK4/6is on SCLC chemoresistance. In this study, it is found that CDK4/6is palbociclib (PD) or ribociclib (LEE) combined with chemotherapeutic drugs significantly inhibit SCLC tumor growth. Mechanistically, CDK4/6is do not function through the classic Retionblastoma1 (RB) dependent axis in SCLC. CDK4/6is induce impair autophagy through the AMBRA1-lysosome signaling pathway. The upregulated AMBRA1 protein expression leads to CDK6 degradation via autophagy,  and the following TFEB and TFE3 nuclear translocation inhibition leading to the lysosome-related genes levels downregulation. Moreover, it is found that the expression of CDK6 is higher in SCLC tumors than in normal tissue and it is associated with the survival and prognosis of SCLC patients. Finally, these findings demonstrate that combining CDK4/6is with chemotherapy treatment may serve as a potential therapeutic option for SCLC patients.