The RAC/ROP GTPase activator OsRopGEF10 functions in crown root development by regulating cytokinin signaling in rice.

RAC/Rho of plant (ROP) GTPases are major molecular switches that control diverse signaling cascades for plant growth, development, and defense. Here, we discovered a signaling node that connects RAC/ROPs to cytokinins. Rice (Oryza sativa) plants develop a fibrous root system mainly composed of crown roots. Cytokinin signaling via a phosphorelay system is critical for crown root development. We show that OsRopGEF10, which activates RAC/ROPs, acts upstream of the cytoplasmic-nuclear shuttling phosphotransfer proteins AHPs of the cytokinin signaling pathway to promote crown root development. Mutations of OsRopGEF10 induced hypersensitivity to cytokinin, whereas overexpressing this gene reduced the cytokinin response. Loss of OsRopGEF10 function reduced the expression of the response regulator gene OsRR6, a repressor of cytokinin signaling, and impaired crown root development. Mutations in OsAHP1/2 led to increased crown root production and rescued the crown root defect of Osropgef10. Furthermore, auxin activates the ROP GTPase OsRAC3, which attenuates cytokinin signaling for crown root initiation. Molecular interactions between OsRopGEF10, OsRAC3, and OsAHP1/2 implicate a mechanism whereby OsRopGEF10-activated OsRAC3 recruits OsAHP1/2 to the cortical cytoplasm, sequestering them from their phosphorelay function in the nucleus. Together, our findings uncover the OsRopGEF10-OsRAC3-OsAHP1/2 signaling module, establish a link between RAC/ROPs and cytokinin, and reveal molecular crosstalk between auxin and cytokinin during crown root development.

Near-Unity Green Luminescent Hybrid Manganese Halides as X-ray Scintillators.

The increasing demands in optoelectronic applications have driven the advancement of organic-inorganic hybrid metal halides (OIMHs), owing to their exceptional optical and scintillation properties. Among them, zero-dimensional (0D) low-toxic manganese-based scintillators have garnered significant interest due to their exceptional optical transparency and elevated photoluminescence quantum yields (PLQYs), making them promising for colorful light-emitting diodes and X-ray imaging applications. In this study, two OIMH single crystals of (Br-PrTPP)2MnBr4 (Br-PrTPP = (3-bromopropyl) triphenylphosphonium) and (Br-BuTPP)2MnBr4 (Br-BuTPP = (4-bromobutyl) triphenylphosphonium) were prepared via a facile saturated crystallization method. Benefiting from the tetrahedrally coordinated [MnBr4]2- polyhedron, both of them exhibited strong green emissions peaked at 517 nm owing to the d-d electron transition of Mn2+ with near-unity PLQYs of 99.33 and 86.85%, respectively. Moreover, benefiting from the high optical transparencies and remarkable luminescence properties, these manganese halides also exhibit excellent radioluminescent performance with the highest light yield of up to 68,000 photons MeV-1, negligible afterglow (0.4 ms), and linear response to X-ray dose rate with the lowest detection limit of 45 nGyair s-1. In X-ray imaging, the flexible film made by the composite of (Br-PrTPP)2MnBr4 and PDMS shows an ultrahigh spatial resolution of 12.78 lp mm-1, which provides a potential visualization tool for X-ray radiography.

Crystal-Rigidifying Strategy in Hybrid Manganese Halide to Achieve Narrow Green Emission and High Structural Stability.

Although organic-inorganic hybrid Mn2+ halides have advanced significantly, achieving high stability and narrow-band emission remains enormously challenging owing to the weak ionic nature and soft crystal lattice of the halide structure. To address these issues, we proposed a cationic engineering strategy of long-range cation π···π stacking and C-H···π interactions to simultaneously improve the crystal structural stability and rigidity. Herein, two organic zero-dimensional (0D) manganese halide hybrids of (BACQ)2MnX4 [BACQ = 4-(butylamino)-7-chloroquinolin-1-ium; X = Cl and Br] were synthesized. (BACQ)2MnX4 display strong green-light emissions with the narrowest full width at half-maximum (fwhm) of 39 nm, which is significantly smaller than those of commercial green phosphor ß-SiAlON:Eu2+ and most of reported manganese halides. Detailed Hirshfeld surface analyses demonstrate the rigid environment around the [MnX4]2- units originating from the interactions between [BACQ]+. The rigid crystal structure weakens the electron-phonon coupling and renders narrow fwhm of these manganese halides, which is further confirmed by temperature-dependent emission spectra. Remarkably, (BACQ)2MnX4 realizes outstanding structural and luminescence stabilities in various extreme environments. Benefiting from the excellent performance, these Mn2+ halides are used to assemble light-emitting diodes with a wide color gamut of 105% of the National Television System Committee 1931 standard, showcasing the advanced applications in liquid-crystal-display backlighting.

Discovery of a Novel and Potent LCK Inhibitor for Leukemia Treatment via Deep Learning and Molecular Docking.

The lymphocyte-specific protein tyrosine kinase (LCK) plays a crucial role in both T-cell development and activation. Dysregulation of LCK signaling has been demonstrated to drive the oncogenesis of T-cell acute lymphoblastic leukemia (T-ALL), thus providing a therapeutic target for leukemia treatment. In this study, we introduced a sophisticated virtual screening strategy combined with biological evaluations to discover potent LCK inhibitors. Our initial approach involved utilizing the PLANET algorithm to assess and contrast various scoring methodologies suitable for LCK inhibitor screening. After effectively evaluating PLANET, we progressed to devise a virtual screening workflow that synergistically combines the strengths of PLANET with the capabilities of Schrödinger's suite. This integrative strategy led to the efficient identification of four potential LCK inhibitors. Among them, compound 1232030-35-1 stood out as the most promising candidate with an IC50 of 0.43 nM. Further in vitro bioassays revealed that 1232030-35-1 exhibited robust antiproliferative effects on T-ALL cells, which was attributed to its ability to suppress the phosphorylations of key molecules in the LCK signaling pathway. More importantly, 1232030-35-1 treatment demonstrated profound in vivo antileukemia efficacy in a human T-ALL xenograft model. In addition, complementary molecular dynamics simulations provided deeper insight into the binding kinetics between 1232030-35-1 and LCK, highlighting the formation of a hydrogen bond with Met319. Collectively, our study established a robust and effective screening strategy that integrates AI-driven and conventional methodologies for the identification of LCK inhibitors, positioning 1232030-35-1 as a highly promising and novel drug-like candidate for potential applications in treating T-ALL.

Atmospheric Nitrogen Pollution Control Benefits the Coastal Environment.

Nitrogen is an essential nutrient and a major limiting element for the ocean ecosystem. Since the preindustrial era, substantial amounts of nitrogen from terrestrial sources have entered the ocean via rivers, groundwater, and atmospheric deposition. China serves as a key hub in the global nitrogen cycle, but the pathways, sources, and potential mitigation strategies for land-ocean nitrogen transport are unclear. By combining the CHANS, WRF-Chem, and WNF models, we estimated that 8 million tonnes (Tg) of nitrogen was transferred into the ocean in 2017 in China, with atmospheric deposition contributing 1/3. About half variation of the offshore chlorophyll concentration was explained by atmospheric deposition. The Bohai Sea was the hot spot of nitrogen input, estimated at 214 kg N ha-1, while other areas were around 25-51 kg N ha-1. The largest contributors are agricultural systems (4 Tg, 55%), followed by domestic sewage (2 Tg, 21%). Abatement measures could reduce nitrogen export to the ocean by 43%, and mitigating ammonia and nitrogen oxide emissions accounts for 33% of this reduction, highlighting the importance of addressing air pollution in resolving ocean pollution. The cost-benefit analysis suggests the priority of nitrogen reduction in cropland and transport systems for the ocean environment.

SMAD4 endows TGF-ß1-induced highly invasive tumor cells with ferroptosis vulnerability in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy prone to recurrence and metastasis. Studies show that tumor cells with increased invasive and metastatic potential are more likely to undergo ferroptosis. SMAD4 is a critical molecule in the transforming growth factor ß (TGF-ß) pathway, which affects the TGF-ß-induced epithelial-mesenchymal transition (EMT) status. SMAD4 loss is observed in more than half of patients with PDAC. In this study, we investigated whether SMAD4-positive PDAC cells were prone to ferroptosis because of their high invasiveness. We showed that SMAD4 status almost determined the orientation of transforming growth factor ß1 (TGF-ß1)-induced EMT via the SMAD4-dependent canonical pathway in PDAC, which altered ferroptosis vulnerability. We identified glutathione peroxidase 4 (GPX4), which inhibited ferroptosis, as a SMAD4 down-regulated gene by RNA sequencing. We found that SMAD4 bound to the promoter of GPX4 and decreased GPX4 transcription in PDAC. Furthermore, TGF-ß1-induced high invasiveness enhanced sensitivity of SMAD4-positive organoids and pancreas xenograft models to the ferroptosis inducer RAS-selective lethal 3 (RSL3). Moreover, SMAD4 enhanced the cytotoxic effect of gemcitabine combined with RSL3 in highly invasive PDAC cells. This study provides new ideas for the treatment of PDAC, especially SMAD4-positive PDAC.

Cpd-A1 alleviates acute kidney injury by inhibiting ferroptosis.

Acute kidney injury (AKI) is defined as sudden loss of renal function characterized by increased serum creatinine levels and reduced urinary output with a duration of 7 days. Ferroptosis, an iron-dependent regulated necrotic pathway, has been implicated in the progression of AKI, while ferrostatin-1 (Fer-1), a selective inhibitor of ferroptosis, inhibited renal damage, oxidative stress and tubular cell death in AKI mouse models. However, the clinical translation of Fer-1 is limited due to its lack of efficacy and metabolic instability. In this study we designed and synthesized four Fer-1 analogs (Cpd-A1, Cpd-B1, Cpd-B2, Cpd-B3) with superior plasma stability, and evaluated their therapeutic potential in the treatment of AKI. Compared with Fer-1, all the four analogs displayed a higher distribution in mouse renal tissue in a pharmacokinetic assay and a more effective ferroptosis inhibition in erastin-treated mouse tubular epithelial cells (mTECs) with Cpd-A1 (N-methyl-substituted-tetrazole-Fer-1 analog) being the most efficacious one. In hypoxia/reoxygenation (H/R)- or LPS-treated mTECs, treatment with Cpd-A1 (0.25 µM) effectively attenuated cell damage, reduced inflammatory responses, and inhibited ferroptosis. In ischemia/reperfusion (I/R)- or cecal ligation and puncture (CLP)-induced AKI mouse models, pre-injection of Cpd-A1 (1.25, 2.5, 5 mg·kg-1·d-1, i.p.) dose-dependently improved kidney function, mitigated renal tubular injury, and abrogated inflammation. We conclude that Cpd-A1 may serve as a promising therapeutic agent for the treatment of AKI.

Dynamics of carbon storage driven by land use/land cover transformation in coal mining areas with a high groundwater table: A case study of Yanzhou Coal Mine, China.

Intensive anthropogenic activities have led to drastic changes in land use/land cover (LULC) and impacted the carbon storage in high-groundwater coal basins. In this paper, we conduct a case study on the Yanzhou Coalfield in Shandong Province of China. We further classify waterbodies by using the Google Earth Engine (GEE) to better investigate the process of LULC transformation and the forces driving it in four periods from 1985 to 2020 (i.e., 1985-1995, 1995-2005, 2005-2015, and 2015-2020). We modeled the spatiotemporal dynamics of carbon storage by using InVEST based on the transformation in LULC and its drivers, including mining (M), reclamation (R), urbanization and village relocation (U), and ecological restoration (E). The results indicate that carbon storage had depleted by 19.69 % (321099.06 Mg) owing to intensive transformations in LULC. The area of cropland shrank with the expansion of built-up land and waterbodies, and 56.31 % of the study area underwent transitions in land use in the study period. U was the primary driver of carbon loss while E was the leading driver of carbon gain. While the direct impact of M on carbon loss accounted for only 5.23 % of the total, it affected urbanization and led to village relocation. R led to the recovery of cropland and the reclamation of water for aquaculture, which in turn improved the efficiency of land use. However, it contributed only 2.09 % to the total increase in carbon storage. Numerous complicated and intertwined processes (211) drove the changes in carbon storage in the study area. The work here provides valuable information for decision-makers as well as people involved in reclamation and ecological restoration to better understand the link between carbon storage and the forces influencing it. The results can be used to integrate the goals of carbon sequestration into measures for land management.

Mechanism through which the hsa-circ_0000992- hsa- miR- 936-AKT3 regulatory network promotes the PM2.5-induced inflammatory response in human bronchial epithelial cells.

BACKGROUND: Studies have shown that fine particulate matter (PM2.5) remains a significant problem in developing countries and plays a critical role in the onset and progression of respiratory illnesses. Circular RNAs (circRNAs) are involved in many pathophysiological processes,but their relationship to PM2.5 pollution is largely unexplored. OBJECTIVES: To elucidate the functional role of hsa_circ_0000992 in PM2.5-induced inflammation in a human bronchial epithelial cell line (16HBE) and to clarify whether the competing endogenous RNA (ceRNA) mechanism is involved in the interrelationships between hsa_circ_0000992 and hsa-miR-936 and the inflammatory signaling pathways. METHODS: Detection of inflammatory factors in 16HBE cells exposed to PM2.5 by RT-qPCR and ELISA.High throughput sequencing and bioinformatics analysis methods were used to screen circRNA.The bioinformatics analysis method western blotting and dual-luciferase reporter gene system were used to verify mechanisms associated with circRNA. RESULTS: PM2.5 cause inflammation in the 16HBE cells. High throughput sequencing and RT-qPCR result revealed that the expression of hsa_circ_0000992 was markedly up-regulated in 16HBE exposed to PM2.5. The binding sites between hsa_circ_0000992 and hsa-miR-936 was confirmed by dual-luciferase reporter gene system.Western blotting and RT-qPCR showed that hsa_circ_0000992 can interact with hsa-miR-936 to regulate AKT serine/threonine kinase 3(AKT3),thereby activating the PI3K/AKT pathway and ultimately promoting the expression of interleukin (IL)- 1ß and IL-8. CONCLUSION: PM2.5 can induce the inflammatory response in 16HBE cells by activating the PI3K/AKT pathway. The expression of hsa_circ_0000992 increased when PM2.5 stimulated 16HBE cells,and the circRNA could then regulate the inflammatory response.Hsa_circ_0000992 regulates the hsa-miR-936/AKT3 axis through the ceRNA mechanism,thereby activating the PI3K/AKT signaling pathway,increasing the expression of cellular inflammatory factors,and promoting PM2.5-induced respiratory inflammation.

Personality traits and co-occurrence of depressive symptoms and high BMI: a prospective cohort study.

We assess the associations between personality traits and co-occurrence of depressive symptoms and high BMI from adolescence to early adulthood. We employed a nationally representative cohort in China from 2010 to 2020 year. We included adolescents aged 10-19 years without depressive symptoms and unhealthy weight status (obesity, overweight, or thinness) at baseline and excluded those without any measurement of depressive symptoms or BMI at follow-ups. We assessed baseline personality traits in 7 dimensions of conscientiousness, openness, neuroticism, agreeableness, extraversion, self-esteem, and responsibility. We also assessed the combined effects of these 7 dimensions of personality traits by generating individual-level personality trait risk scores based on the weighted sum of all these 7 dimensions of personality traits. We measured the co-occurrence of depressive symptoms and high BMI using both a single measurement of depressive symptoms and BMI at the last follow-up and repeated measurements of them over 10 years. We used the multinomial logistic regression models to examine the exposure-outcome associations. At baseline, we included 1778 individuals (mean age: 14.4 year; female: 853 (48.0%)). At follow-ups, we observed increased risk of co-occurrence of depressive symptoms and high BMI per 1-SD increase in neuroticism score (1.95-2.38 odds ratio) or 1-SD decrease in self-esteem and conscientiousness (0.63-0.80 odds ratio; all P values < 0.05); we observed no evidence of associations between openness, agreeableness, extraversion, or responsibility and the risk of co-occurrence of depressive symptoms and high BMI (all P values > 0.05). For the combined effects of the 7 dimensions of personality traits, we found an elevated risk of co-occurrence of depressive symptoms and high BMI per 1-SD increase in the personality trait risk scores (OR (95% CI), single measurement at the last follow-up: 2.01, 1.66 to 2.43; trajectory classification using the repeated measurements 2.30, 1.55 to 3.42; average level using the repeated measurements: 2.27, 1.93 to 2.67). In this national cohort in China, personality traits were found to be associated with the co-occurrence of depressive symptoms and high BMI from adolescence to early adulthood. These findings highlight the importance of stratifying individuals based on their personality traits and providing targeted interventions for those at risk of comorbid depression and obesity.

A randomized trial of Bacteroides fragilis 839 on preventing chemotherapy-induced myelosuppression and gastrointestinal adverse effects in breast cancer patients.

BACKGROUND AND OBJECTIVES: To evaluate the potential benefits of Bacteroides fragilis 839 (BF839), a next-generation probiotics, in reducing myelosuppression and gastrointestinal toxicity associated with chemotherapy in breast cancer patient. METHODS AND STUDY DESIGN: 40 women with early breast cancer were randomly assigned to the BF839 (n=20) or placebo (n=20) during the administration of adjuvant chemotherapy (4 cycles of epirubicin 100mg/m2 and cyclophosphamide 600mg/m2). Myelosuppression and gastrointestinal adverse effects were monitored in both groups. RESULTS: Throughout the four treatment cycles, the percentage of patients experiencing myelosuppression was 42.5% in the BF839 group, significantly lower than the 66.3% observed in the control group (p=0.003). Two patients in the BF839 group and three patients in the placebo group received recombinant human granulocyte colony-stimulating factor (rhG-CSF) due to leuko-penia/neutropenia. When considering an ITT analysis, which included all patients regardless of rhG-CSF treatment, the BF839 group exhibited less reduction from baseline in white blood cells (-0.31±1.19 vs -1.15±0.77, p=0.012) and neutrophils (0.06±1.00 vs -0.84±0.85, p=0.004) compared to the placebo group. The difference became even more significant when excluding the patients who received rhG-CSF injections. Throughout the four treatment cycles, compared to the placebo group, the BF839 group had significantly lower rates of 3-4 grade nausea (35.0% vs 71.3%, p=0.001), vomiting (20.0% vs 45.0%, p=0.001), and diarrhea (15.0% vs 30.0%, p=0.023). CONCLUSIONS: These findings suggest that BF839 has the potential to effectively mitigate myelosuppression and gastrointestinal toxicity associated with chemotherapy in breast cancer patients.

Microwave ablation versus laparoscopic resection as first-line therapy for solitary 3-5-cm HCC.

BACKGROUND AND AIMS: The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3-5-cm HCC over time. APPROACH AND RESULTS: From 2008 to 2019, 1289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology. Propensity score matching was used to balance all baseline variables between the two groups in 2008-2019 (n = 335 in each group) and 2014-2019 (n = 257 in each group) cohorts, respectively. For cohort 2008-2019, during a median follow-up of 35.8 months, there were no differences in overall survival (OS) between MWA and LLR (HR: 0.88, 95% CI 0.65-1.19, p = 0.420), and MWA was inferior to LLR regarding disease-free survival (DFS) (HR 1.36, 95% CI 1.05-1.75, p = 0.017). For cohort 2014-2019, there was comparable OS (HR 0.85, 95% CI 0.56-1.30, p = 0.460) and approached statistical significance for DFS (HR 1.33, 95% CI 0.98-1.82, p = 0.071) between MWA and LLR. Subgroup analyses showed comparable OS in 3.1-4.0-cm HCCs (HR 0.88, 95% CI 0.53-1.47, p = 0.630) and 4.1-5.0-cm HCCs (HR 0.77, 95% CI 0.37-1.60, p = 0.483) between two modalities. For both cohorts, MWA shared comparable major complications (both p > 0.05), shorter hospitalization, and lower cost to LLR (all p < 0.001). CONCLUSIONS: MWA might be a first-line alternative to LLR for solitary 3-5-cm HCC in selected patients with technical advances, especially for patients unsuitable for LLR.

High Emission Efficiency and Thermal Stability in Zero-Dimensional Hybrid Zinc Halide as a Blue Light Emitter.

Exploring highly efficient blue-emissive lead-free halide materials is a significant and challenging objective in the study of luminescent materials. This study reports the synthesis of a new zero-dimensional (0D) hybrid zinc halide of [CYP]ZnBr4 (CYP = 1-cyclohexylpiperazine) containing an isolated [ZnBr4]2- tetrahedron. [CYP]ZnBr4 exhibits strong blue light emission with a high photoluminescence quantum yield (PLQY) of 79.22%, surpassing all previously reported 0D zinc halide counterparts. According to the theoretical and experimental studies, the blue light emission is attributed to intrinsic self-trapped excitons resulting from strong electron-phonon coupling and structural deformation. Importantly, [CYP]ZnBr4 demonstrates excellent structural and luminescence stability toward high temperatures (180 °C) over at least half a month. High luminescence efficiency and stability enable [CYP]ZnBr4 to be an efficient blue phosphor to fabricate white light-emitting diodes (LEDs), which produces high-quality white light with a color rendering index (CRI) of 93.1 and a correlated color temperature (CCT) of 5304 K, closely resembling natural sunlight. This white LED also exhibits consistent performance and stability across different drive currents, suggesting the potential for high-power optoelectronic applications. Overall, this study paves the way for the utilization of 0D hybrid halides in advanced solid-state lighting applications.

Self-Pumping Janus Hydrogel with Aligned Channels for Accelerating Diabetic Wound Healing.

Excessive exudate secreted from diabetic wounds often results in skin overhydration, severe infections, and secondary damage upon dressing changes. However, conventional wound dressings are difficult to synchronously realize the non-maceration of wound sites and rapid exudate transport due to their random porous structure. Herein, a self-pumping Janus hydrogel with aligned channels (JHA) composed of hydrophilic poly (ethylene glycol) diacrylate (PEGDA) hydrogel layer and hydrophobic polyurethane (PU)/graphene oxide (GO)/polytetrafluoroethylene (PTFE) layer is designed to rapidly export exudate and accelerate diabetic wound healing. In the design, the ice-templating process endows the hydrophilic hydrogel layer with superior liquid transport ability and mechanical strength due to the formation of aligned channel structure. The hydrophobic layer with controlled thickness functions as an effective barrier to prevent exudate from wetting the skin surface. Experiments in diabetic rat model show that JHA can significantly promote re-epithelialization and collagen deposition, shorten the inflammation phase, and accelerate wound healing. This unique JHA dressing may have great potential for real-life usage in clinical patients.

Hernandezine induces autophagic cell death in human pancreatic cancer cells via activation of the ROS/AMPK signaling pathway.

Hernandezine (Her) is a bisbenzylisoquinoline alkaloid extracted from the traditional Chinese herbal medicine Thalictrum glandulosissimum. Evidence shows that Her is a natural agonist of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and induces apoptosis and autophagy in tumor cells. In this study, we investigated the role of autophagy in Her-induced cell death in human pancreatic cancer cell lines. We showed that Her dose-dependently suppressed cell proliferation, promoted autophagy and induced autophagic death in pancreatic ductal adenocarcinoma (PDAC) cell lines Capan-1 and SW1990. The IC50 values of Her in inhibition of Capan-1 and SW1990 cells were 47.7 µM and 40.1 µM, respectively. Immunoblotting showed that Her (1-40 µM) promoted the conversion of LC3-I to LC3-II, and Her exerted concentration-dependent and time-dependent effects on autophagy activation in PDAC cells. In transmission electron microscopy and fluorescence image analysis, we found that autophagic vacuoles were significantly increased in Her-treated cells. Knockdown of ATG5, a key gene in the autophagy pathway, alleviated the activation of autophagy by Her. These results demonstrated that Her induced autophagy in PDAC cells. Intensely activated autophagy could promote cell death. The autophagy inhibitors, BafA1 and HCQ significantly inhibited Her-induced cell death, implying that Her induced autophagic cell death in PDAC cells. Moreover, we showed that Her activated autophagy by increasing the phosphorylation of AMPK and decreasing the phosphorylation of mTOR/p70S6K. Knockdown of AMPKα relieves the autophagic cell death induced by Her. Furthermore, Her concentration-dependently enhanced reactive oxygen species (ROS) generation in PDAC cells. Antioxidants could reduce the phosphorylation of AMPK and suppress autophagic cell death induced by Her. Our study provides evidence for the development of Her as a therapeutic agent for the treatment of pancreatic cancer.

A new glance at autophagolysosomal-dependent or -independent function of transcriptional factor EB in human cancer.

Autophagy-lysosome system plays a variety of roles in human cancers. In addition to being implicated in metabolism, it is also involved in tumor immunity, remodeling the tumor microenvironment, vascular proliferation, and promoting tumor progression and metastasis. Transcriptional factor EB (TFEB) is a major regulator of the autophagy-lysosomal system. With the in-depth studies on TFEB, researchers have found that it promotes various cancer phenotypes by regulating the autophagolysosomal system, and even in an autophagy-independent way. In this review, we summarize the recent findings about TFEB in various types of cancer (melanoma, pancreatic ductal adenocarcinoma, renal cell carcinoma, colorectal cancer, breast cancer, prostate cancer, ovarian cancer and lung cancer), and shed some light on the mechanisms by which it may serve as a potential target for cancer treatment.

Perioperative and oncologic outcomes of laparoscopic versus open liver resection for combined hepatocellular-cholangiocarcinoma: a propensity score matching analysis.

BACKGROUND: Laparoscopic liver resection (LLR) has now been established as a safe and minimally invasive technique that is deemed feasible for treating hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). However, the role of LLR in treating combined hepatocellular-cholangiocarcinoma (cHCC-CC) patients has been rarely reported. This study aimed to assess the efficacy of LLR when compared with open liver resection (OLR) procedure for patients with cHCC-CC. METHODS: A total of 229 cHCC-CC patients who underwent hepatic resection (34 LLR and 195 OLR patients) from January 2014 to December 2018 in Zhongshan Hospital, Fudan University were enrolled and underwent a 1:2 propensity score matching (PSM) analysis between the LLR and OLR groups to compare perioperative and oncologic outcomes. Overall survival (OS) and recurrence-free survival (RFS) parameters were assessed by the log-rank test and the sensitivity analysis. RESULTS: A total of 34 LLR and 68 OLR patients were included after PSM analysis. The LLR group displayed a shorter postoperative hospital stay (6.61 vs. 8.26 days; p value < 0.001) when compared with the OLR group. No significant differences were observed in the postoperative complications' incidence or a negative surgical margin rate between the two groups (p value = 0.409 and p value = 1.000, respectively). The aspartate aminotransferase (AST), alanine aminotransferase (ALT), and inflammatory indicators in the LLR group were significantly lower than those in the OLR group on the first and third postoperative days. Additionally, OS and RFS were comparable in both the LLR and OLR groups (p value = 0.700 and p value = 0.780, respectively), and similar results were obtained by conducting a sensitivity analysis. CONCLUSION: LLR can impart less liver function damage, better inflammatory response attenuation contributing to a faster recovery, and parallel oncologic outcomes when compared with OLR. Therefore, LLR can be recommended as a safe and effective therapeutic modality for treating selected cHCC-CC patients, especially for those with small tumors in favorable location.

Identification of competing endogenous RNA network in laryngeal squamous cell carcinoma.

OBJECTIVE: This study was conducted to investigate key long noncoding RNAs (lncRNAs) involved in competitive endogenous RNA (ceRNA) network associated with laryngeal squamous cell carcinoma (LSCC). MATERIALS AND METHODS: Three mRNA datasets, two miRNA datasets, and one lncRNA dataset of LSCC were downloaded from GEO database. Following the identification of differentially expressed mRNAs (DEmRNAs), (microRNAs) miRNAs (DEmiRNAs), and lncRNAs (DElncRNAs) in LSCC compared with adjacent tissues, functional enrichment of DEmRNAs was performed. Then, construction of the ceRNA (DElncRNA-DEmiRNA-DEmRNA) regulatory network and functional analyses of all DEmRNAs in ceRNA regulatory network were conducted. Quantitative real-time polymerase chain reactions (qRT-PCR) were used to detect the expression levels of selected DEmRNAs, DEmiRNAs, and DElncRNAs. RESULTS: A total of 3449 DEmRNAs, 40 DEmiRNAs, and 100 DElncRNAs were identified in LSCC. The ceRNA networks, which contained 132 DElncRNA-DEmiRNA pairs and 287 DEmiRNA-DEmRNA pairs, involving 44 lncRNAs, 3 miRNAs, and 271 mRNAs, were obtained. DEmRNAs in ceRNA regulatory networks were significantly enriched in pathways in cancer, prostate cancer, and aldosterone-regulated sodium reabsorption. Except for HCG22 and hsa-miR-1246, expressions of the others in the qRT-PCR results played the same pattern with that in our integrated analysis, generally. CONCLUSIONS: We concluded that HCG22/EGOT-hsa-miR-1275-FAM107A and HCG22/EGOT-hsa-miR-1246-Glycerol-3-phosphate dehydrogenase 1 like interaction pairs may play a central role in LSCC.

Using POI and time series Landsat data to identify and rebuilt surface mining, vegetation disturbance and land reclamation process based on Google Earth Engine.

The development of coal resources is necessary, but it has a huge negative impact on land, ecology, and the environment. With the increasing awareness of environmental protection and the requirements of related regulations, the design and practice of reclamation projects run through the mining life cycle and continue for a long time after the coal production. High-precision monitoring of mining disturbance and reclamation, quantifying the degree and time of vegetation disturbance and restoration, is of great significance to minimize the environmental effect of mining. Remote sensing, widely used as efficient monitoring tool, but there is not enough research on disturbance and reclamation monitoring taking into account large-scale areas and high temporal and spatial accuracy. Especially when mining sites remain unknown, how to distinguish the disturbance of coal mining and other human activities affecting the surface land cover has become a challenge. Therefore, this paper proposed a method to reconstruct the time series of mining disturbance and reclamation in a large area by using the POI (point of interest) and Landsat time series images using multiple buffer analysis methods. The process includes: (1) Retrieval of POI in the study area based on the public mining list using Python crawler, and buffering 100 km for preliminary extraction of potential mining areas; (2) Using spectral index mask and random forest algorithm to accurately extract the exposed coal on the Google Earth Engine (GEE) platform; (3) Buffering 10 km to identify the occurrence of disturbance and reclamation, using pixel-based temporal trajectory identification of LandTrendr algorithm under GEE. The method successful detect the change points of surface coal mining disturbance and reclamation in eastern Inner Mongolia of China. The results show that: (1) The method can effectively identify the extent of surface coal mining disturbance and reclamation, and the overall extraction accuracy is 81%. (2) Surface coal mining disturbance in eastern Inner Mongolia was concentrated in 2006-2011. By 2020, the total disturbed area is 627.8 km2, with an average annual disturbance of 18.5 km2, and the annual maximum disturbance to the ground reached 64.6 km2 in 2008. With the total reclaimed area being 236.3 km2, the reclamation rate is about 37.6%. This study provides a systematic solution and process for monitoring the disturbance and reclamation of surface coal mining in a large range with little known about the mines' location. It can effectively identify the mining disturbance and reclamation process which can also be extended to other areas, providing a quantitative assessment of mining disturbance and reclamation, which can support further ecological restoration decision-making.

[Clinical observation of transurethral holmium laser enucleation of prostate by two-way rendezvous and trenching].

OBJECTIVE: Exploring the clinical efficacy, safety, and surgical techniques of two-way rendezvous and trenching method for transurethral holmium laser prostatectomy in the treatment of benign prostatic hyperplasia. METHODS: Retrospective analysis of clinical data on preoperative, intraoperative, and postoperative follow-up of 326 patients with benign prostatic hyperplasia who underwent two-way rendezvous and trenching method of transurethral holmium laser prostatectomy at the Urology Department of Wujin People's Hospital in Changzhou City from January 2020 to January 2023. RESULTS: Compared with preoperative measures, IPSS symptom score, quality of life (QoL) score, maximum urinary flow rate (Qmax), and residual urine volume (PVR) were significantly improved at 1, 6, and 12 months postoperatively (P<0.05). Thirty two patients with normal and regular sexual life pre-operation were observed. There were no significant changes in their IIEF-5 score and Erectile Hardness Scale (EHGS) score after surgery compared with pre-operation (P<0.05). There were 9 patients (28.12%) with retrograde ejaculation after surgery. CONCLUSION: The two-way rendezvous and trenching method of transurethral holmium laser prostatectomy is a safe and effective method for treating benign prostatic hyperplasia, with precise results, high safety, minimal trauma, and fast postoperative recovery.