METTL16 deficiency attenuates apoptosis through translational control of extrinsic death receptor during nutrient deprivation.

METTL16 is a well-characterized m6A methyltransferase that has been reported to contribute to tumorigenesis in various types of cancer. However, the effect of METTL16 on tumor progression under restricted nutrient conditions, which commonly occur in tumor microenvironment, has yet to be elucidated. Herein, our study initially reported the inhibitory effect of METTL16 depletion on apoptosis under amino acid starvation conditions. Mechanistically, we determined that the METTL16 knockdown represses the expression of extrinsic death receptors at both transcription and translation levels. Depletion of METTL16 prevented protein synthesis of GCN2, resulting in diminished ATF4 expression in a GCN2-eIF2α-dependent manner. Reduction of ATF4 further declined the expression of apoptotic receptor protein DR5. Meanwhile, METTL16 deficiency directly hampered protein synthesis of FADD and DR5, thereby impairing apoptosis and promoting cancer cell survival. Taken together, our study provides novel evidence for the involvement of METTL16 in regulating cancer progression, suggesting that METTL16 as a potential therapeutic target for cancer treatment.

Pre- vs Post-Operative Levator Ani Subtended Volume in Patients Undergoing Hysterectomy: A Comparative Imaging Study.

INTRODUCTION AND HYPOTHESIS: The effects of hysterectomy on pelvic floor function remain uncertain, with the levator ani muscle (LAM) playing a critical role in pelvic support. The levator ani subtended volume (LASV) is an objective measure of the LAM's anatomical volume, derived from magnetic resonance imaging (MRI). This study was aimed at assessing the consistency between MRI and computed tomography (CT) in quantifying LASV, and to investigate the effect of hysterectomy on the LAM. METHODS: This retrospective study analyzed a cohort of 55 hysterectomy patients, utilizing pre-operative pelvic MRI and post-operative CT scans to measure the LASV. To evaluate the consistency between MRI and CT, the study employed the intraclass correlation coefficient and Bland-Altman agreement analysis in a subset of 32 patients with both pre-operative scans. A paired-samplet test was used to analyze LASV changes pre- and post-hysterectomy, and linear regression analysis was performed to account for potential risk factors that may influence post-operative LASV. RESULTS: High consistency between MRI and CT in measuring LASV was found, with an ICC of 0.911. We observed a significant increase in LASV following hysterectomy, with mean volume pre- and post-operatively of 16.66 cm3 and 18.87 cm3 respectively. Age and body mass index were significant predictors of post-hysterectomy LASV, whereas parity and the type of hysterectomy had no significant impact. CONCLUSIONS: Hysterectomy significantly affects the LAM, resulting in an increase in post-operative LASV. Moreover, this study verifies that MRI and CT can be used interchangeably for LASV measurements in clinical practice.

Effect of maternal vaccination on infant morbidity in Bangladesh.

BACKGROUND: Risk factors of infant mortality in Africa and south Asian countries have been broadly discussed. However, infant morbidity is largely underestimated. We analyzed the data from a randomized vaccine trial in Bangladesh to identify and assess the effect of risk factors on infant morbidity. METHODS: Pregnant women were randomly assigned to receive either inactivated influenza vaccine or pneumococcal polysaccharide vaccine and the infants were randomly assigned to receive 7-valent pneumococcal conjugate vaccine or Hib conjugate vaccine at week 6, 10 and 14. The data were collected from August 2004 through December 2005. Each pair of infant and mother were followed for 24 weeks after birth with weekly visits. Generalized estimating equations (GEE) for repeated measurements and Poisson regression models were used to identify the risk factors and evaluate their effect on the longitudinal incidence and total number of episodes of respiratory illness with fever (RIF), diarrhea disease, ear problem and pneumonia. RESULTS: A total of 340 pregnant women were randomized with mean age of 25 years. The baseline mother and infant characteristics were similar between two treatment groups. Exclusive breastfeeding and higher paternal education level were common factors associated with lower infant morbidity of RIF (adjusted OR = 0.40 and 0.94 with p < 0.01 and p = 0.02, respectively), diarrhea disease (adjusted OR = 0.39 and 0.95 with p < 0.01 and p = 0.04, respectively), and ear problem (adjusted OR = 0.20 and 0.76 with p < 0.01 and p < 0.01, respectively). Maternal influenza vaccine significantly reduced the incidence of RIF (adjusted OR = 0.54; p < 0.01) but not diarrhea disease or ear problem (p > 0.05). Female infants had lower incidence of diarrhea disease (adjusted OR = 0.67; p = 0.01) and ear problem (adjusted OR = 0.12; p = 0.01). CONCLUSIONS: Maternal influenza vaccination, exclusive breastfeeding, female children, and higher paternal education level significantly reduced the infant morbidity within the 24 weeks after birth in Bangladesh.

Extremely Large Response of Phonon Coherence in Twisted Penta-NiN2 Bilayer.

Twisting has recently been demonstrated as an effective strategy for tuning the interactions between particles or quasi-particles in layered materials. Motivated by the recent experimental synthesis of pentagonal NiN2 sheet [ACS Nano 2021, 15, 13539], for the first time, the response of phonon coherence to twisting in bilayer penta-NiN2 , going beyond the particle-like phonon transport is studied. By using the unified theory of phonon transport and high order lattice anharmonicity, together with the self-consistent phonon theory, it is found that the lattice thermal conductivity is reduced by 80.6% from 33.35 to 6.47 W m-1 K-1 at 300 K when the layers are twisted. In particular, the contribution of phonon coherence is increased sharply by an order of magnitude, from 0.21 to 2.40 W m-1 K-1 , due to the reduced differences between the phonon frequencies and enhanced anharmonicity after the introduction of twist. The work provides a fundamental understanding of the phonon interaction in twisted pentagonal sheets.

Decomposition of SO2 on Ni(111) Surface and the Effect of Metal Doping: A First-Principles Study.

Sulfides poisoning of metallic Ni is an important issue in catalyst deactivation. SO2, similar to H2S and other sulfides, is an impurity presented in reactants or during the regeneration steps. Herein, spin-polarized density functional theory calculations were used to study the adsorption and decomposition of SO2 on a pristine and metal-doped Ni(111) surface. The adsorption energy, transition state energy, and partial density of state (PDOS) were calculated. On the pristine Ni(111) surface, ten different configurations were considered, and three typical ones were selected for transition state searching. It was found that the reaction barrier of the first S-O bond dissociation was much higher than that of the second one. Doping the top layer with a second metal could strongly change the adsorption and decomposition behavior. Doping with 3/9ML Co slightly increases the adsorption energy of SO2 for most configurations and decreases the reaction barriers of the SO2-tht-2 decomposition, while the others decrease the adsorption ability and increase the barriers. The order of adsorption energy for the most stable configurations is Co > Ni > Cu > Rh > Pd. The order of the first S-O bond dissociation reaction barriers is Pd > Rh > Cu = Ni > Co, and the order of the second bond dissociation barrier is Rh > Pd > Cu > Ni > Co.

Persistence Infection of TGEV Promotes Enterococcus faecalis Infection on IPEC-J2 Cells.

Transmissible gastroenteritis virus (TGEV) is a coronavirus causing diarrhea with high incidence in swine herds. Its persistent infection might lead to epithelial-mesenchymal transition (EMT) of swine intestinal epithelial cells, followed by subsequent infections of other pathogens. Enterococcus faecalis (E. faecalis) is a member of the enteric microorganisms and an opportunistic pathogen. There is no report of secondary E. faecalis infection to TGEV, even though they both target to the intestinal tracts. To investigate the interactions between TGEV and E. faecalis, we set up an in vitro infection model by the swine IPEC-J2 cells. Dynamic changes of cell traits, including EMT and cell motility, were evaluated through qPCR, Western blot, electronic microscopy, scratch test, Transwell migration test and invasion test, respectively. The adhesion and invasion tests of E. faecalis were taken to verify the impact of the preceding TGEV infection. The cell morphology and molecular marker evaluation results showed that the TGEV persistent infection induced EMT on IPEC-J2 cells; increased cellular motility and invasion potential were also observed. Spontaneously, the expression levels of fibronectin (FN) and the membrane protein integrin-α5, which are dominant bacterial receptors on IPEC-J2 cells, were upgraded. It indicated that the bacteria E. faecalis adhered to IPEC-J2 cells through the FN receptor, and then invaded the cells by binding with the integrin-α5, suggesting that both molecules were critical for the adhesion and invasion of E. faecalis to IPEC-J2 cells. Additionally, it appeared that E. faecalis alone might trigger certain EMT phenomena, implying a vicious circle might occur. Generally, bacterial and viral co-infections are frustrating yet common in both human and veterinary medicines, and our observations on enteric TGEV and E. faecalis interactions, especially the diversity of bacterial invasion strategies, might provide new insights into the mechanisms of E. faecalis pathogenicity.

LncRNA CASC21 induces HGH1 to mediate colorectal cancer cell proliferation, migration, EMT and stemness.

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Long non-coding RNAs (lncRNAs) have been increasingly reported to serve vital parts in malignancies including CRC. Although cancer susceptibility 21 (CASC21) has been uncovered to play a part in CRC, its mechanism still needs further explanation. Thus, our study aimed to further explore the influence and mechanism of CASC21 in CRC progression. Quantitative real-time RT-PCR and western blot were performed to detect gene expression; a series of functional assays were performed to investigate the effect of CASC21 on CRC cells; in vivo tumour growth was evaluated via the nude mice xenograft model. The results revealed that CASC21 facilitated CRC cell proliferation, migration, epithelial-mesenchymal transition (EMT) and stemness. In addition, CASC21 was co-expressed with and bound to transcription factor POU5F1B (POU class 5 homeobox 1B). CASC21 recruited POU5F1B to HGH1 promoter to activate the transcription of HGH1 homolog. Also, CASC21 served as a competitive endogenous RNA (ceRNA) to up-regulate HGH1 via endogenously sponging miR-485-5p. Moreover, HGH1 overexpression counteracted the suppression of CASC21 deficiency on CRC tumour growth. In summary, our study indicated that CASC21 enhanced the expression of HGH1 to promote the malignancy of CRC by recruiting POU5F1B and sponging miR-485-5p, suggesting a key role of CASC21 in CRC progression.

Silencing of Proteasome 26S Subunit ATPase 2 Regulates Colorectal Cancer Cell Proliferation, Apoptosis, and Migration.

OBJECTIVE: Colorectal cancer (CRC) remains a major cause of cancer-related death worldwide. Proteasome 26S subunit ATPase 2 (PSMC2) plays vital roles in regulating cell cycle and transcription and has been confirmed to be a gene potentially associated with some human tumors. However, the expression correlation and molecular mechanism of PSMC2 in CRC are still unclear. This study aimed to investigate the role of PSMC2 in malignant behaviors in CRC. METHODS: The high protein levels of PSMC2 in CRC samples were identified by tissue microarray analysis. Lentivirus was used to silence PSMC2 in HCT116 and RKO cells; MTT and colony formation assay were performed to determine cell proliferation. Wound healing and Transwell assay were used to detect cell migration and invasion. Flow cytometry assay was applied to detect cell cycle and apoptosis. RESULT: The results showed that, among the 96 CRC patients, the expression of PSMC2 was a positive correlation with the clinicopathological features of the patients with CRC. Furthermore, the low PSMC2 expression group showed a higher survival rate than the high PSMC2 expression group. The expression levels of PSMC2 in cancer tissue were dramatically upregulated compared with adjacent normal tissues. In vitro, shPSMC2 was designed to inhibit the expression of PSMC2 in CRC cells. Compared with shCtrl, silencing of PSMC2 significantly suppressed cell proliferation, decreased single cell colony formation, enhanced apoptosis, and accelerated G2 phase and/or S phase arrest. CONCLUSION: Survival analysis indicated that high expression of PSMC2 in the CRC samples was associated with poorer survival rate than low expression of PSMC2, while the anti-tumor effect of PSMC2 silencing was also confirmed at the cellular level in vitro. Our results suggested that PSMC2 potentially worked as a regulator for CRC, and the silencing of PSMC2 may be a therapeutic strategy for CRC.

Quantitative analysis of modified functional muscle-bone unit and back muscle density in patients with lumbar vertebral fracture in Chinese elderly men: a case-control study.

OBJECTIVES: Bone mineral density (BMD) is associated with muscle mass and quality, but little research has been done on functional muscle-bone unit and back muscle density in patients with lumbar vertebral fracture. This study used the "modified functional muscle-bone unit" concept and measured back muscle density to investigate muscle-bone interaction difference between the fracture and control group. METHODS: This was a case-control study. A total of 52 elderly male patients (mean age 75 years) with lumbar vertebral fracture (cases) and 52 control healthy subjects were enrolled. Cross-sectional area (CSA) and density of paravertebral muscle were measured in quantitative computed tomography (QCT) images to represent the muscle mass, while the bone mineral density measured by QCT was used to represent the bone mass. The modified functional muscle-bone unit was calculated as the value of volumetric BMD divided by muscle area. RESULTS: People with vertebral fractures reported significantly lower values in the cross-sectional area and density of paravertebral muscle compared to control group. In the multivariate analysis, BMD (odds ratio, OR = 0.929; 95% confidence intervals, CIs 0.888-0.971), erector muscle density (OR = 0.698; 95% CI 0.547-0.892), and summated muscle CSA (OR = 0.963; 95% CI 0.93-0.991) were independent protective factors for the presence of a fracture. BMD resulted significantly and moderately associated with cross-sectional area and density of paravertebral muscle (r = 0.329-0.396). CONCLUSIONS: There were significant differences between the modified functional muscle-bone unit and back muscle density between the fracture group and control group in elderly men. Lower BMD, loss of muscle mass and density are associated with increased presence of the lumbar vertebral fracture.

Validation of goose liver fat measurement by QCT and CSE-MRI with biochemical extraction and pathology as reference.

OBJECTIVES: This study aimed to validate the accuracy and reliability of quantitative computed tomography (QCT) and chemical shift encoded magnetic resonance imaging (CSE-MRI) to assess hepatic steatosis. METHODS: Twenty-two geese with a wide range of hepatic steatosis were collected. After QCT and CSE-MRI examinations, the liver of each goose was removed and samples were taken from the left lobe, upper and lower half of the right lobe for biochemical measurement and histology. Fat percentages by QCT and proton density fat fraction by MRI (MRI-PDFF) were measured within the sample regions of biochemical measurement and histology. The accuracy of QCT and MR measurements were assessed through Spearman correlation coefficients (r) and Passing and Bablok regression equations using biochemical measurement as the "gold standard". RESULTS: Both QCT and MRI correlated highly with chemical extraction [r = 0.922 (p < 0.001) and r = 0.949 (p < 0.001) respectively]. Chemically extracted triglyceride was accurately predicted by both QCT liver fat percentages (Y = 0.6 + 0.866 × X) and by MRI-PDFF (Y = -1.8 + 0.773 × X). CONCLUSIONS: QCT and CSE-MRI measurements of goose liver fat were accurate and reliable compared with biochemical measurement. KEY POINTS: • QCT and CSE-MRI can measure liver fat content accurately and reliably • Histological grading of hepatic steatosis has larger sampling variability • QCT and CSE-MRI have potential in the clinical setting.

CXCR5+CD8+ T cells infiltrate the colorectal tumors and nearby lymph nodes, and are associated with enhanced IgG response in B cells.

Colorectal cancer is the third most prevalent cancer type worldwide and contributes to a significant percentage of cancer-related mortality. Recent studies have shown that the CXCR5+CD8+ T cells present more potent proinflammatory function than CXCR5-CD8+ T cells in chronic virus infections and in follicular lymphoma, but the role of CXCR5+CD8+ T cells in colorectal cancer is yet unclear. In this study, we demonstrated that CXCR5+CD8+ T cells were very rare in peripheral blood mononuclear cells from healthy and colorectal cancer individuals, but were significantly enriched in resected tumors and tumor-associated lymph nodes. Compared to CXCR5-CD8+ T cells, the CXCR5+CD8+ T cells demonstrated significantly higher Bcl-6 expression and lower Blimp1 expression, suggesting that CXCR5+CD8+ T cells might represent a memory CD8+ T cell subset. CXCR5+CD8+ T cells also enhanced the IgG expression by autologous B cells. Under ex vivo condition, the CXCR5+CD8+ T cells demonstrated lower degranulation, TNFα expression and IFNγ expression than CXCR5-CD8+ T cells. However, after PMA + ionomycin stimulation, the degranulation and TNFα expression by CXCR5+CD8+ T cells were significantly elevated to a level comparable with CXCR5-CD8+ T cells, whereas the IFNγ expression by PMA + ionomycin-stimulated CXCR5+CD8+ T cells were significantly higher than that by CXCR5-CD8+ T cells. Following long-term TCR-stimulation, CXCR5+CD8+ T cells demonstrated significantly more potent proliferation capacity and higher IFNγ expression than CXCR5-CD8+ T cells. TCR-stimulated CXCR5+CD8+ T cells also showed a gradual downregulation in CXCR5 expression. We further found that TCR-stimulated CXCR5+CD8+ T cells demonstrated higher granzyme B production and induced more specific lysis of autologous tumor cells than CXCR5-CD8+ T cells. Together, these data demonstrate that CXCR5+CD8+ T cells represent a significant CD8+ T cell subset in colorectal tumors and have the potential to contribute to antitumor immunity, but their specific roles require further studies in vivo.

Antihypoxic effect of miR-24 in SH-SY5Y cells under hypoxia via downregulating expression of neurocan.

Hypoxia-induced apoptosis-related mechanisms involved in the brain damage following cerebral ischemia injury. A subset of the small noncoding microRNA (miRNAs) is regulated by tissue oxygen levels, and miR-24 was found to be activated by hypoxic conditions. However, the roles of miR-24 and its target gene in neuron are not well understood. Here, we validated miRNA-24 is down-regulated in patients with cerebral infarction. Hypoxia suppressed the expression of miR-24, but increased the expression of neurocan in both mRNA and protein levels in SH-SY5Y cells. MiR-24 mimics reduced the expression of neurocan, suppressed cell apoptosis, induced cell cycle progression and cell proliferation in SH-SY5Y cells under hypoxia. By luciferase reporter assay, neurocan is validated a direct target gene of miR-24. Furthermore, knockdown of neurocan suppressed cell apoptosis, induced cell cycle progression and cell proliferation in SH-SY5Y cells under hypoxia. Taken together, miR-24 overexpression or silencing of neurocan shows an antihypoxic effect in SH-SY5Y cells. Therefore, miR-24 and neurocan play critical roles in neuron cell apoptosis and are potential therapeutic targets for ischemic brain disease.

Biocomposite based on graphene oxide immobilized Pseudomonas psychrotolerans for the recovery of Y(III) in acid mine drainage.

Rare earth elements (REEs) recovery is a critical issue concerning both resource recovery and wastewater utilization. In this study, a new bio-composite was fabricated using graphene oxide immobilized Pseudomonas psychrotolerans (PP@GO), which was isolated from the soil of REEs mine. Results showed that 99.6% Y(III) was removed in 48 h and various characterization confirmed that S-S, -NH2, HPO42-, -OH and -COOH from extracellular polymeric substances (EPS) secreted by microorganisms formed complexation with Y(III). As well, the Y(III) adsorption best followed Freundlich isotherm and non-linear pseudo-second-order kinetic model having R2 of 0.985 and 0.996, respectively, demonstrating that the adsorption was governed by multilayered chemisorption. Additionally, the effectiveness of PP@GO was not limited to Y(III), where 27.9% of this substance was removed in acid mine drainage (AMD), also exhibited great adsorption for other REEs, such as Er (45.0%) and Ho (43.8%). Furthermore, the adsorption efficiency of Y(III) remained high (70.0%) after a 5th cycle, emphasizing the consistent stability of PP@GO. Finally, REEs adsorbed could be greatly desorbed by KNO3, like Sm (80.1%) and La (80.0%), which revealed that PP@GO has great potential to recover REEs in AMD. Overall, this study offers a promising strategy for the green and sustainable REEs recovery and wastewater treatment.

Recovery of rare earth elements from mine wastewater using alginate microspheres encapsulated with zeolitic imidazolate framework-8.

There is increasing demand and interest in efficient methods for the recovery of rare earth elements (REEs) from wastewater because of the growing concerns associated with the negative impacts of REEs-rich waste discharged on pristine ecosystems. Here, we designed a ZIF-8@ALG composite hydrogel by encapsulating zeolitic imidazolate frameworks-8 (ZIF-8) into sodium alginate and poly (vinyl alcohol) double cross-linked networks (ALG) for the recovery of REEs from mine wastewater. ZIF-8@ALG showed exceptional REEs adsorption performance with the most superior separation factor (Ho/Mn) of 597.5. For the REEs considered, the ZIF-8@ALG composite exhibited a preference for heavy REEs with high adsorption efficiencies (65.3 ∼ 97.2%) and distribution coefficients (2045.5 ∼ 28500.0 mL·g-1). Adsorption involved a combination of electrostatic attraction, complexation and ion exchange mechanisms. REEs adsorbed on ZIF-8@ALG could also be desorbed using sodium citrate via ion-exchange and complexation, thus achieving efficient REEs recovery. In addition, ZIF-8@ALG was stable and reusable, maintaining effective adsorption in wastewater over four consecutive cycles, where the optimal adsorption efficiency reached 80.0%. Overall, this study provided an effective and feasible method for the recovery of REEs in mine wastewater, and confirmed that ZIF-8-based materials have significant potential for REEs recovery applications in wastewater engineering treatment.

Association Between Social Determinants of Health and Cancer Treatment Delay in an Urban Population.

PURPOSE: Delays in oncologic time to treatment initiation (TTI) independently and adversely affect disease-specific mortality. Social Determinants of Health (SDoH) are increasingly recognized as significant contributors to patients' disease management and health outcomes. Our academic center has validated a 10-item SDoH screener, and we elucidated which specific needs may be predictive of delayed TTI. METHODS: This is a retrospective cohort study at an urban academic center of patients with a SDoH screening and diagnosis of breast, colorectal, endocrine/neuroendocrine, GI, genitourinary, gynecologic, head and neck, hematologic, hepatobiliary, lung, or pancreatic cancer from 2018 to 2022. Variables of interest included household income, tumor stage, and emergency department (ED) or inpatient admission 30 days before diagnosis. Factors associated with delayed TTI ≥45 days were assessed using multivariable logistic regression. RESULTS: Among 2,328 patients (mean [standard deviation] age, 64.0 (12.8) years; 66.6% female), having >1 unmet social need was associated with delayed TTI (odds ratio [OR], 1.68; 95% CI, 1.54 to 1.82). The disparities most associated with delay were legal help, transportation, housing stability, and needing to provide care for others. Those with ED (OR, 0.49; 95% CI, 0.44 to 0.54) or inpatient (OR, 0.54; 95% CI, 0.50 to 0.58) admission 30 days before diagnosis were less likely to experience delay. CONCLUSION: Delays in oncologic TTI ≥45 days are independently associated with unmet social needs. ED or inpatient admissions before diagnosis increase care coordination, leading to improved TTI. Although limitations included the retrospective nature of the study and self-reporting bias, these findings more precisely identify targets for intervention that may more effectively decrease delay. Patients with SDoH barriers are at higher risk of treatment delay and could especially benefit from legal, transportation, caregiver, and housing assistance.

Development of an "on-off-on" fluoroprobe utilizing an anthrylimidazole-based fluorescent ionic liquid for sensitive Cr(VI) and ascorbic acid detection.

Developing a rapid detection method of Cr(VI) and ascorbic acid (AA) is vital in the food and environmental fields. Herein, an anthrylimidazole-based fluorescent ionic liquid (AI-FIL) with the advantageous fluorescent properties was successfully prepared and used to construct a promising "on-off-on" fluoroprobe for rapid/sensitive Cr(VI) and AA detection. Cr(VI) could effectively quench the fluorescence of AI-FIL owing to the inner-filter effect and photoinduced electron-transfer process. However, the decreased fluorescence could be rapidly recovered by AA owing to the redox reaction between AA and Cr(VI). For Cr(VI) detection, a satisfactorily linear response (0.03-300 µM) was achieved with the corresponding detection limit of 9 nM. For AA detection, a good linearity from 1 to 1000 µM was obtained with the resultant detection limit of 0.3 µM. Moreover, the AI-FIL based fluoroprobe was successfully utilized for Cr(VI) and AA detection in food and water samples with satisfactory accuracy and precision.

Sedimentary Paleoenvironment and Organic Matter Enrichment Characteristics of Lacustrine Shahezi Shale in Songliao Basin: Insights from the Continental Scientific Drilling.

The lacustrine shale of the Shahezi Formation in the Songliao Basin has obvious organic matter enrichment characteristics and great potential for oil and gas resources. At present, the understanding of the sedimentary paleoenvironment and organic matter enrichment characteristics of the lacustrine shale of the Shahezi Formation is relatively weak. Therefore, taking the international continental scientific drilling Program (ICDP) borehole Songke-2 (SK-2) with continuous and whole Shahezi cores as the research object, combined with organic geochemistry, elemental geochemistry, and logging data, the sedimentary paleoenvironment and organic matter enrichment mechanism were studied. The results show that the organic matter of Shahezi shale is generally in the high to over mature stage. The kerogen type of organic matter is mainly II2-III. The organic matter is mainly derived from the lake basin's own algae and terrestrial higher plants. The total organic carbon (TOC) content of Shahezi shale is relatively high, and the TOC is mainly distributed between 1% and 2%. The Shahezi Formation is dominated by clay shale and siliceous shale, and experienced moderate chemical weathering during deposition. According to the analysis of organic geochemistry and elemental geochemistry data, the paleoenvironment of organic matter deposition in Shahezi shale was dominated by warm and humid climate in the early stage, and then experienced multiple cooling and arid periods. The climate type turned to semihumid-semiarid, with stable terrigenous debris input, low deposition rate, brackish water salinity and oxygen-rich-oxygen-poor water environment. The sedimentary period of Shahezi Formation is in the Cretaceous oceanic anoxic Aptian-Albian stage. During the oceanic anoxic event, the anoxic sedimentary environment and the frequent volcanic activity have an important impact on the organic matter enrichment. The oceanic anoxic event and volcanic activity are the main causes of water body hypoxia in the lake basin. The nutrients brought by volcanic activity are also one of the reasons for promoting the growth of lake basin organisms, creating good conditions for organic matter enrichment. The enrichment of organic matter in Shahezi Formation is the result of the interaction and coupling of various factors such as paleoclimate, paleoenvironment, paleoproductivity, water environment, terrestrial input, and major geological events. And, the organic matter enrichment model of Shahezi Formation shale is established.

Immunotherapy Efficacy in Advanced Hepatocellular Carcinoma in a Diverse and Underserved Population in the United States.

Background :   Incidence of hepatocellular cancer (HCC) in the Bronx is 61% higher than the rest of New York State. Underserved populations are not well represented in clinical trials of immune checkpoint inhibitors (ICI). Methods: Demographics were tabulated for 194 patients treated with ICI at the Montefiore-Einstein Comprehensive Cancer Center (MECCC) between 2017 and 2022. Categorical variables were analyzed by Chi-squared test, and survival was analyzed using Kaplan-Meier (KM) curves. Results: MECCC patients were 40.7% Hispanic and 20.6% Black, compared with 3% and 2%, respectively, in the landmark IMbrave 150 study. Median overall survival (mOS) on ICI was 9.0 months, 25.0 months for the 100 (51.5%) favorable-prognosis Child Pugh A (CPA) patients included in HCC clinical trials. Disease control rate (DCR) was 58.5% among 123 evaluable patients per mRECIST 1.1. Baseline liver function, as defined by CP and the Model for End-Stage Liver Disease-Sodium (MELD-Na), correlated with survival (p < 0.001). Hepatitis C Virus (HCV) and alcoholism were over-represented relative to National Cancer Institute (NCI) data (56.2% vs 4.7% and 38.7% vs 8.2%, respectively). HCV treatment correlated with prolonged survival in infected patients (p = 0.0017). AFP decline correlated with response (p = 0.001). Hispanic patients lived longer when clinical variables were controlled for (mOS 52 vs 23 months; p = 0.011). Conclusion: In an underserved HCC population, ICI yielded a DCR of 58.5% and low rates of severe toxicity. This work highlights ICI efficacy in minority groups, a need for earlier HCC diagnosis and for studies of genetic and environmental factors in Hispanics with HCC.

Type-1 Pentagonal Tiling Realized in 2D Penta-SrP2 Sheet.

According to the systematic classification of pentagon-based two-dimensional (2D) materials [ Phys. Rep. 2022, 964, 1], only type-2 and type-4 out of the 15 pentagonal tiling patterns have been realized in 2D materials so far. Here, we propose the first stable pentagon-based 2D material characterized by the type-1 pentagonal tiling pattern named penta-SrP2. We find that penta-SrP2 is not only thermally and mechanically stable but also dynamically stable when the temperature is above 200 K derived from the calculations by taking both phonon renormalization and thermal expansion into consideration. Moreover, the penta-SrP2 sheet is semiconducting with an indirect band gap of 0.96 eV. These findings expand the family of pentagon-based 2D materials in morphology and provide a new perspective to explore the dynamical stability of high-temperature phases.

Establishment of a pathomic-based machine learning model to predict CD276 (B7-H3) expression in colon cancer.

CD276 is a promising prognostic indicator and an attractive therapeutic target in various malignancies. However, current methods for CD276 detection are time-consuming and expensive, limiting extensive studies and applications of CD276. We aimed to develop a pathomic model for CD276 prediction from H&E-stained pathological images, and explore the underlying mechanism of the pathomic features by associating the pathomic model with transcription profiles. A dataset of colon adenocarcinoma (COAD) patients was retrieved from the Cancer Genome Atlas (TCGA) database. The dataset was divided into the training and validation sets according to the ratio of 8:2 by a stratified sampling method. Using the gradient boosting machine (GBM) algorithm, we established a pathomic model to predict CD276 expression in COAD. Univariate and multivariate Cox regression analyses were conducted to assess the predictive performance of the pathomic model for overall survival in COAD. Gene Set Enrichment Analysis (GESA) was performed to explore the underlying biological mechanisms of the pathomic model. The pathomic model formed by three pathomic features for CD276 prediction showed an area under the curve (AUC) of 0.833 (95%CI: 0.784-0.882) in the training set and 0.758 (95%CI: 0.637-0.878) in the validation set, respectively. The calibration curves and Hosmer-Lemeshow goodness of fit test showed that the prediction probability of high/low expression of CD276 was in favorable agreement with the real situation in both the training and validation sets (P=0.176 and 0.255, respectively). The DCA curves suggested that the pathomic model acquired high clinical benefit. All the subjects were categorized into high pathomic score (PS) (PS-H) and low PS (PS-L) groups according to the cutoff value of PS. Univariate and multivariate Cox regression analysis indicated that PS was a risk factor for overall survival in COAD. Furthermore, through GESA analysis, we found several immune and inflammatory-related pathways and genes were associated with the pathomic model. We constructed a pathomics-based machine learning model for CD276 prediction directly from H&E-stained images in COAD. Through integrated analysis of the pathomic model and transcriptomics, the interpretability of the pathomic model provide a theoretical basis for further hypothesis and experimental research.