Soluble Programmed Cell Death 1 Protein Is a Promising Biomarker to Predict Severe Liver Inflammation in Chronic Hepatitis B Patients.

Background and Aims: Liver inflammation is important in guiding the initiation of antiviral treatment and affects the progression of chronic hepatitis B(CHB). The soluble programmed cell death 1 protein (sPD-1) was upregulated in inflammatory and infectious diseases and correlated with disease severity. We aimed to investigate the correlation between serum sPD-1 levels and liver inflammation in CHB patients and their role in indicating liver inflammation. Methods: 241 CHB patients who underwent liver biopsy were enrolled. The correlation between sPD-1 levels and the degree of liver inflammation was analyzed. Univariate and multivariate logistic regression analyses were performed to analyze independent variables of severe liver inflammation. Binary logistic regression analysis was conducted to construct a predictive model for severe liver inflammation, and the receiver operating characteristic curve (ROC) was used to evaluate the diagnostic accuracy of the predictive model. Results: sPD-1 was highest in CHB patients with severe liver inflammation, which was higher than that in CHB patients with mild or moderate liver inflammation (P < 0.001). Besides, sPD-1 was weakly correlated with AST (r = 0.278, P < 0.001). Multivariable analysis showed that sPD-1 was an independent predictor of severe liver inflammation. The predictive model containing sPD-1 had areas under the ROC (AUROCs) of 0.917 and 0.921 in predicting severe liver inflammation in CHB patients and CHB patients with ALT ≤ 1× upper limit of normal (ULN), respectively. Conclusions: Serum sPD-1 level is associated with liver inflammation in CHB patients, and high levels of sPD-1 reflect severe liver inflammation. Serum sPD-1 is an independent predictor of severe liver inflammation and shows improved diagnostic accuracy when combined with other clinical indicators.

Complications and local recurrence of chondrosarcoma and chordoma treated by total tumor resection in thoracic and lumbar spine.

BACKGROUND: En bloc resection of spinal tumors is challenging and associated with a high incidence of complications; however, it offers the potential to reduce the risk of recurrence when a wide margin is achieved. This research aims to investigate the safety and efficacy of en bloc resection in treating thoracic and lumbar chondrosarcoma/chordoma. METHODS: Data from patients diagnosed with chondrosarcoma and chordoma in the thoracic or lumbar region, who underwent total en bloc or piecemeal resection at our institution over a 7-year period, were collected and regularly followed up. The study analyzed overall perioperative complications and compared differences in complications and local tumor recurrence between the two surgical methods. RESULTS: Seventeen patients were included, comprising 12 with chondrosarcoma and 5 with chordoma. Among them, 5 cases underwent intralesional piecemeal resection, while the remaining 12 underwent planned en bloc resection. The average surgical time was 684 min (sd = 287), and the mean estimated blood loss was 2300 ml (sd = 1599). Thirty-five complications were recorded, with an average of 2.06 perioperative complications per patient. 82% of patients (14/17) experienced at least one perioperative complication, and major complications occurred in 64.7% (11/17). Five patients had local recurrence during the follow-up, with a mean recurrence time of 16.2 months (sd = 7.2) and a median recurrence time of 20 months (IQR = 12.5). Hospital stays, operation time, blood loss, and complication rates did not significantly differ between the two surgical methods. The local recurrence rate after en bloc resection was lower than piecemeal resection, although not statistically significant (P = 0.067). CONCLUSIONS: The complication rates between the two surgical procedures were similar. Considering safety and local tumor control, en bloc resection is recommended as the primary choice for patients with chondrosarcoma/chordoma in the thoracic and lumbar regions who are eligible for this treatment.

Catalytic dehydrogenative coupling and reversal of methanol-amines: advances and prospects.

The development of efficient hydrogen release and storage processes to provide environmentally friendly hydrogen solutions for mobile energy storage systems (MESS) stands as one of the most challenging tasks in addressing the energy crisis and environmental degradation. The catalytic dehydrogenative coupling of methanol and amines (DCMA) and its reverse are featured by high capacity for hydrogen release and storage, enhanced capability to purify the produced hydrogen, avoidance of carbon emissions and singular product composition, offering the environmentally and operationally benign strategy of overcoming the challenges associated with MESS. Particularly, the cycle between these two processes within the same catalytic system eliminates the need for collecting and transporting spent fuel back to a central facility, significantly facilitating easy recharging. Despite the promising attributes of the above strategy for environmentally friendly hydrogen solutions, challenges persist, primarily due to the high thermodynamic barriers encountered in methanol dehydrogenation and amide hydrogenation. By systematically summarizing various reaction mechanisms and pathways involving Ru-, Mn-, Fe-, and Mo-based catalytic systems in the development of catalytic DCMA and its reverse and the cycling between the two, this review highlights the current research landscape, identifies gaps, and suggests directions for future investigations to overcome these challenges. Additionally, the critical importance of developing efficient catalytic systems that operate under milder conditions, thereby facilitating the practical application of DCMA in MESS, is also underscored.

Impact of Sarcopenia on Prognosis in Primary Hepatocellular Carcinoma Patients Treated with Transcatheter Arterial Chemoembolization: A Single Center Retrospective Study.

Objective: This study aimed to investigate the prognostic effect of sarcopenia on primary hepatocellular carcinoma (HCC) patients after transcatheter arterial chemoembolization (TACE). Methods: This retrospective study enrolled 265 patients diagnosed with HCC who underwent TACE between April 2014 and February 2021. The patients were divided into two groups: the sarcopenia group (n=133) and the non-sarcopenia group (n=132). The study analyzed the differences in overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier curves. The independent risk factors for OS and PFS were determined using univariate and multivariate Cox regression analysis. Based on these factors, the study constructed a prognostic risk grading system. Results: At 3 and 6 months post-TACE, the prognoses of the sarcopenia group were worse than that of the non-sarcopenia group according to the mRECIST criteria. Kaplan-Meier curves showed that the cumulative OS and PFS rate in the non-sarcopenia group were significantly higher compared to the sarcopenia group (HR=3.319, 95%CI: 2.283-4.824, Log-rank P < 0.001; HR=0.631, 95%CI: 0.486-0.820, Log-rank P < 0.001). Sarcopenia, maximal tumor diameter, and AFP ≥ 200 ng/mL were independent risk factors for OS and PFS. The prognostic risk grading system based on sarcopenia, AFP ≥ 200 ng/mL, and maximal tumor diameter≥8.9 cm showed significant differences in prognosis between risk groups. Conclusion: Sarcopenia had excellent predictive value for OS and PFS in patients after TACE, and AFP ≥ 200 ng/mL and maximal tumor diameter were also independent risk factors for a poor prognosis. The prognostic risk grading system based on sarcopenia, AFP, and maximal tumor diameter had good guiding value for the prognosis of patients.

Nanodrug delivery systems for regulating microglial polarization in ischemic stroke treatment: A review.

The incidence of ischemic stroke (IS) is rising in tandem with the global aging population. There is an urgent need to delve deeper into the pathological mechanisms and develop new neuroprotective strategies. In the present review, we discuss the latest advancements and research on various nanodrug delivery systems (NDDSs) for targeting microglial polarization in IS treatment. Furthermore, we critically discuss the different strategies. NDDSs have demonstrated exceptional qualities to effectively permeate the blood-brain barrier, aggregate at the site of ischemic injury, and target specific cell types within the brain when appropriately modified. Consequently, NDDSs have considerable potential for reshaping the polarization phenotype of microglia and could be a prospective therapeutic strategy for IS. The treatment of IS remains a challenge. However, this review provides a new perspective on neuro-nanomedicine for IS therapies centered on microglial polarization, thereby inspiring new research ideas and directions.

A comparative study on the age, growth, and mortality of Gobio huanghensis (Luo, Le & Chen, 1977) in the Gansu and Ningxia sections of the upper Yellow River, China.

BALKGROUND: Gobio huanghensis is a small economic fish endemic to the Yellow River at the junction of the Tibetan Plateau and the Huangtu Plateau in China. To understand the impact of environmental changes and human activities on the ecological structure of the G. huanghensis population, a comparative study was conducted on the age composition, growth characteristics, mortality rate, and exploitation rate of the G. huanghensis populations in the Gansu and Ningxia sections of the upper Yellow River. RESULTS: During the investigation, a total of 1147 individuals were collected, with 427 individuals collected from the Gansu section and 720 individuals from the Ningxia section. The results showed that G. huanghensis in the Gansu section exhibited a total length ranging from 5.00 to 22.80 cm, with an average of 12.68 ± 4.03 cm. In the Ningxia section, the total length of G. huanghensis ranged from 2.15 to 20.65 cm, with an average of 9.48 ± 3.56 cm. The age composition of G. huanghensis in the Gansu section ranged from 1 to 7 years, where female fish were observed between 1 and 7 years old, and male fish between 1 and 6 years old. In the Ningxia section, both female and male fish ranged from 1 to 5 years old. The relationships between total length and body weight were (Gansu section, R2 = 0.9738) and (Ningxia section, R2 = 0.9686), indicating that fish in the Gansu section exhibit positive allometric growth, while fish in the Ningxia section exhibit negative allometric growth. The von Bertalanffy growth equation revealed that G. huanghensis in the Gansu section exhibited an asymptotic total length L∞ of 27.426 cm with a growth coefficient K of 0.225 yr-1, while in the Ningxia section, the asymptotic total length L∞ was 26.945 cm with a growth coefficient K of 0.263 yr-1. The total mortality rate (Z) values of G. huanghensis were 0.7592 yr and 1.1529 yr in the Gansu section and Ningxia section, respectively. The average natural mortality rate (M), estimated by three different methods, in the Gansu section was 0.4432 yr, while it was 0.5366 yr in the Ningxia section. The exploitation rate (E) of G. huanghensis was 0.4163 in the Gansu section and 0.5345 in the Ningxia section, indicating that the population in the Ningxia section may have been overexploited. CONCLUSION: Prolonged fishing pressures and environmental changes may have led to variations in the ecological parameters of the G. huanghensis population between the Gansu and Ningxia sections.

Activation of AMPK pathway by low­dose donafenib and atorvastatin combination improves high­fat diet­induced metabolic dysfunction­associated steatotic liver disease.

Metabolic dysfunction­associated steatotic liver disease (MASLD) is an increasingly significant global health burden for which there is currently no effective treatment. The present study aimed to explore the underlying mechanisms and investigate the effects of donafenib and atorvastatin in MASLD. The effects of donafenib and atorvastatin on the activity and lipid metabolism of HepG2 cells were analyzed in vitro. A rat model of MASLD was established induced by a high­fat diet in vivo. H&E and Oil red O staining were used to observe the improvement in MASLD, western blotting analysis was used to detect the expression of proteins related to fat metabolism and immunofluorescence was used to detect reactive oxygen species (ROS) levels. In vitro, donafenib and atorvastatin inhibited lipid accumulation in HepG2 cells. In vivo, donafenib and atorvastatin activated the AMP­activated protein kinase (AMPK) pathway, downregulated the expressions of proteins related to fatty acid synthesis (sterol regulatory element­binding protein­1, 3­hydroxy­3­methylglutaryl­CoA reductase and fatty acid synthase) and upregulated the expression of proteins related to fatty acid ß­oxidation (carnitine palmitoyl­transferase 1C and acyl­CoA oxidase). The levels of free fatty acids, cholesterol and triglycerides in the liver and serum decreased in all three treatment groups. Additionally, donafenib and atorvastatin reduced oxidative stress in the liver tissue and decreased ROS levels. Low­dose donafenib combined with atorvastatin improved MASLD by regulating fatty acid metabolism and reducing oxidative stress through activation of the AMPK signaling pathway.

Transcranial ultrasound estimation of viscoelasticity and fluidity in brain tumors aided by transcranial shear waves.

Cerebral diseases, such as brain tumors, are intricately linked to the mechanical properties of brain tissues. Estimating the mechanical properties of brain tumors using transcranial ultrasound is a promising approach. However, the complexity of cranial features introduces challenges, such as ultrasound attenuation and interference from multidirectional transcranial shear waves induced by impact vibrations. To address these issues, this study proposes a transcranial ultrasound estimation method assisted by transcranial shear vibrations. Transcranial vibrations apply shear forces on the parietal bone, inducing unidirectional transcranial shear waves within brain tissue, as validated through simulations. Shear waves at different frequencies were captured via transcranial ultrasound, which were used to assess the viscoelasticity and fluidity of brain tumors. Transcranial experimental validations were conducted in 3D-printed models with tumor phantoms and ex vivo animal tumors. Vibration safety assessments were also performed. The results demonstrate that transcranial ultrasound can detect micron displacements induced by transcranial shear waves. In phantom and ex vivo animal experiments, speed distribution maps were employed to determine the size and location of one or two tumors enclosed in the skull model. The results revealed that the proposed approach could detect tumors with a minimum diameter of 0.8 cm and an inter-tumor distance of 0.8 cm. Notably, significant differences in viscoelasticity and fluidity between normal brain tissue and brain tumors were found (p<0.001). The maximum assessment errors for the elasticity, viscosity, and fluidity using transcranial ultrasound were 11.90%, 4.82%, and 0.73%, respectively, indicating that fluidity was more robust than viscoelasticity. The maximum accelerations of the skull were only 3.21 ms-2.

Effect of a magnetic field on droplet freezing and frost formation on cold surfaces.

The effect of a magnetic field on condensed droplet freezing and frost formation was investigated using visualized experimental devices in this study. The size, shape, freezing time of droplets, and frost shape on the magnetic field considerably differ from those on the nonmagnetic surface. Moreover, the magnetic field could suppress droplet freezing and frost formation. The magnetic field suppression effect on droplet freezing and frost formation was analyzed according to the polarity characteristics of water molecules.

New dammarane-type triterpenoids from the whole plant of Euphorbia hypericifolia.

Euphorhypenoids A (1) and B (2), two new dammarane-type triterpenoids, along with four known tetracyclic triterpenoids (3-6), were isolated from the whole plant of Euphorbia hypericifolia. The structures of new compounds were mainly elucidated by a series of extensive spectroscopic methods, including HR-ESI-MS, NMR, IR, and UV. Compound 1 exhibited significant inhibitory effect on platelet aggregation at concentrations of 10 - 200 µM.

Nano-Micron Combined Hydrogel Microspheres: Novel Answer for Minimal Invasive Biomedical Applications.

Hydrogels, key in biomedical research for their hydrophilicity and versatility, have evolved with hydrogel microspheres (HMs) of micron-scale dimensions, enhancing their role in minimally invasive therapeutic delivery, tissue repair, and regeneration. The recent emergence of nanomaterials has ushered in a revolutionary transformation in the biomedical field, which demonstrates tremendous potential in targeted therapies, biological imaging, and disease diagnostics. Consequently, the integration of advanced nanotechnology promises to trigger a new revolution in the realm of hydrogels. HMs loaded with nanomaterials combine the advantages of both hydrogels and nanomaterials, which enables multifaceted functionalities such as efficient drug delivery, sustained release, targeted therapy, biological lubrication, biochemical detection, medical imaging, biosensing monitoring, and micro-robotics. Here, this review comprehensively expounds upon commonly used nanomaterials and their classifications. Then, it provides comprehensive insights into the raw materials and preparation methods of HMs. Besides, the common strategies employed to achieve nano-micron combinations are summarized, and the latest applications of these advanced nano-micron combined HMs in the biomedical field are elucidated. Finally, valuable insights into the future design and development of nano-micron combined HMs are provided.

Ginkgetin exhibits antifibrotic effects by inducing hepatic stellate cell apoptosis via STAT1 activation.

Liver fibrosis affects approximately 800 million patients worldwide, with over 2 million deaths each year. Nevertheless, there are no approved medications for treating liver fibrosis. In this study, we investigated the impacts of ginkgetin on liver fibrosis and the underlying mechanisms. The impacts of ginkgetin on liver fibrosis were assessed in mouse models induced by thioacetamide or bile duct ligation. Experiments on human LX-2 cells and primary mouse hepatic stellate cells (HSCs) were performed to explore the underlying mechanisms, which were also validated in the mouse models. Ginkgetin significantly decreased hepatic extracellular matrix deposition and HSC activation in the fibrotic models induced by thioacetamide (TAA) and bile duct ligation (BDL). Beneficial effects also existed in inhibiting hepatic inflammation and improving liver function. In vitro experiments showed that ginkgetin markedly inhibited HSC viability and induced HSC apoptosis dose-dependently. Mechanistic studies revealed that the antifibrotic effects of ginkgetin depend on STAT1 activation, as the effects were abolished in vitro after STAT1 silencing and in vivo after inhibiting STAT1 activation by fludarabine. Moreover, we observed a meaningful cross-talk between HSCs and hepatocytes, in which IL-6, released by ginkgetin-induced apoptotic HSCs, enhanced hepatocyte proliferation by activating STAT3 signaling. Ginkgetin exhibits antifibrotic effects by inducing HSC apoptosis via STAT1 activation and enhances hepatocyte proliferation secondary to HSC apoptosis via the IL-6/STAT3 pathway.

Phase Control and Singlet Energy Transfer Enabled by Trimethylamine Modified Boron Dipyrromethene for Stable CsPbBr3 Quantum Wells.

The phase distribution and organic spacer cations play pivotal roles in determining the emission performance and stability of perovskite quantum wells (QWs). Here, we propose a universal molecular regulation strategy to tailor phase distribution and enhance the stability of CsPbBr3 QWs. The capability of sterically hindered ligands with formidable surface binding groups is underscored in directing CsPbBr3 growth and refining phase distribution. With trimethylamine modified boron dipyrromethene (BDP-TMA) ligand as a representative, the BDP-TMA driven can precisely control phase distribution and passivate defects of CsPbBr3 . Notably, BDP-TMA acts as a co-spacer organic entity in obtained BDP-TMA-CsPbBr3 , facilitating efficient singlet energy transfer and tailoring the luminescence to produce a distinctive bluish-white emission. The BDP-TMA-CsPbBr3 demonstrates significant phase stability under water exposure, light irradiation, and moderate temperature. Interestingly, BDP-TMA-CsPbBr3 exhibits the thermally-induced dynamic fluorescence control at elevated temperatures, which can be achieved feasible for advanced information encryption. This discovery paves the way for the exploration of perovskite QWs in applications like temperature sensing, anti-counterfeiting, and other advanced optical smart technologies.

Noninvasive assessment of pressure distribution and fractional flow in middle cerebral artery using microbubbles and plane wave in vitro.

Fractional flow has been proposed for quantifying the degree of functional stenosis in cerebral arteries. Herein, subharmonic aided pressure estimation (SHAPE) combined with plane wave (PW) transmission was employed to noninvasively estimate the pressure distribution and fractional flow in the middle cerebral artery (MCA) in vitro. Consequently, the effects of incident sound pressure (peak negative pressures of 86-653 kPa), pulse repetition frequency (PRF), number of pulses, and blood flow rate on the subharmonic pressure relationship were investigated. The radio frequency data were stored and beamformed offline, and the subharmonic amplitude over a 0.4 MHz bandwidth was extracted using a 12-cycle PW at 4 MHz. The optimal incident sound pressure was 217 kPa without skull (sensitivity = 0.09 dB/mmHg; r2 = 0.997) and 410 kPa with skull (median sensitivity = 0.06 dB/mmHg; median r2 = 0.981). The optimal PRF was 500 Hz, as this value affords the highest sensitivity (0.09 dB/mmHg; r2 = 0.976) and temporal resolution. In addition, the blood flow rate exhibited a lesser effect on the subharmonic pressure relationship in our experimental setup. Using the optimized parameters, the blood pressure distribution and fractional flow (FFs) were measured. As such, the FFs value was in high agreement with the value measured using the pressure sensor (FFm). The mean ± standard deviations of the FF difference (FFm - FFs) were 0.03 ± 0.06 without skull and 0.01 ± 0.05 with skull.

Acetic acid-driven synthesis of environmentally stable MAPb0.5Sn0.5Br3 nano-assembly for anti-counterfeiting.

In mixed Sn-Pb perovskites, the synergistic properties of tin (Sn) and lead (Pb) are leveraged, effectively combining the merits of Pb-based perovskites while simultaneously reducing Pb-associated toxicity. However, the propensity for Sn to undergo facile oxidation from Sn2+ to Sn4+ poses a significant challenge to the stability of these mixed perovskites, limiting their advancement. This study proposes an innovative acetic acid (HAc)-driven synthesis approach to obtain a stable chain-like MAPb0.5Sn0.5Br3 nano-assembly. Leveraging the acidic properties of HAc serves a dual purpose. Primarily, it curtails the oxidation of Sn2+ to Sn4+. Secondly, it orchestrates nanocrystals (NCs) into a more uniform and ordered chain-like assembly, a consequence of hydrogen bonding and coordination interactions facilitated by the HAc. Additionally, HAc demonstrates its capability to passivate MAPb0.5Sn0.5Br3 surface through coordination bonding with unsaturated sites (i.e., Sn2+ or Pb2+), thus effectively compensating for bromide vacancies. Introducing HAc during the synthesis process yields perovskite NCs with enhanced thermal resilience, optical and water stability. Drawing upon the different stimulus responses of synthesized perovskite NCs when exposed to external environment, the optical anti-counterfeiting labels are prepared. The findings provide a potent strategy for augmenting the stability of perovskite NCs, suggesting their potential applicability in anti-counterfeiting endeavors.

Liver inflammation activity in patients with autoimmune hepatitis with normal alanine aminotransferase and immunoglobulin G levels.

Background and aims: Normal serum transaminases and immunoglobulin G (IgG) levels are surrogate markers for hepatic histologic disease activity in autoimmune hepatitis (AIH). This study aimed to evaluate liver inflammation in patients with AIH with normal serum alanine aminotransferase (ALT) and IgG levels. Methods: Two hundred and five AIH patients who underwent liver biopsy in four medical centers were included. Logistic regression analysis was used to identify risk factors associated with advanced inflammation. Results: One hundred and thirty-one (63.9 %) AIH patients had advanced liver inflammation, and 108 (52.7 %) patients had advanced liver fibrosis. 60.0 % of patients with normal ALT and 51.7 % of patients with normal ALT and IgG had advanced inflammation. However, 76.7 % and 35.0 % of patients with or without advanced fibrosis with normal ALT had advanced inflammation, while the corresponding proportions of advanced inflammation were 78.6 % and 26.7 % in patients with normal ALT and IgG, respectively. Moreover, 81.0 % and 44.8 % of patients with and without cirrhosis with normal ALT had advanced inflammation, while the corresponding proportions were 83.3 % and 29.4 % in patients with normal ALT and IgG, respectively. Red cell distribution width (OR = 1.325, 95%CI 1.045-1.681, P = 0.020) and PT (OR = 1.514, 95%CI 1.138-2.014, P = 0.004) were independent factors associated with advanced inflammation. Conclusions: High proportion of advanced inflammation was found in AIH patients with normal ALT and IgG levels despite without advanced fibrosis. Although using non-invasive methods may contribute to rule out liver fibrosis in AIH patients with normal ALT and IgG levels, liver biopsy is encouraged to assess liver inflammation.

Histological features of chronic hepatitis B patients with normal alanine aminotransferase according to different criteria.

BACKGROUND: The upper limits of normal (ULNs) for alanine aminotransferase (ALT) are different among international guidelines for chronic hepatitis B (CHB). We aimed to investigate the proportion of significant histological disease in Asian patients with CHB with detectable hepatitis B virus (HBV) DNA under diverse ALT ULNs. METHODS: Consecutive patients with CHB and detectable HBV DNA who underwent liver biopsy were retrospectively included from four tertiary hospitals. Above grade 2 inflammation and stage 2 fibrosis were defined as significant inflammation and significant fibrosis, respectively. Significant histological disease was defined as above grade 2 inflammation or stage 2 fibrosis. RESULTS: Among the 414 patients with detectable HBV DNA and normal ALT, the proportion of those with significant histological disease was lower (59.7%) according to the ULN for ALT at 30/19 U/L (male/female), while the corresponding proportions were 66.7% and 62.3% according to the ULNs of 40 U/L and 35/25 U/L (male/female), respectively. In patients with detectable HBV DNA and normal ALT levels without significant fibrosis, the proportions of significant inflammation were comparable among different ULNs of ALT at 40 U/L (30.7%), 35/25 U/L (27.3%) and 30/19 U/L (25.0%). The proportion of significant histological disease was significantly lower in patients with normal ALT for 2 determinations at least 6 months apart compared to patients with normal ALT once. CONCLUSIONS: Although a more stringent ALT ULN may reduce the risk of the presence of significant histological disease in patients with detectable HBV DNA, the rates of significant histological disease remain high. Persistently normal ALT levels are more important for excluding patients with CHB with a high probability of significant histological disease.

Freeze-thaw cycles drove chemical weathering and enriched sulfates in the Burns formation at Meridiani, Mars.

Sulfate-rich sedimentary rocks explored by the Opportunity rover during its 14-year surface mission at Meridiani Planum provide an invaluable window into the thousands of sulfate deposits detected on Mars via remote sensing. Existing models explaining the formation of martian sulfates can be generally described as either bottom-up, groundwater-driven playa settings or top-down icy chemical weathering environments. Here, we propose a hybrid model involving both bottom-up and top-down processes driven by freeze-thaw cycles. Freezing leads to cryo-concentration of acidic fluids from precipitations at the surface, facilitating rapid chemical weathering despite low temperatures. Cryosuction causes the upward migration of vadose water and even groundwater with dissolved ions, resulting in the accumulation of ions in near-surface environments. Evaporation precipitates salts, but leaching separates chlorides from sulfates during the thawing period. Freeze-thaw cycles, therefore, can enrich sulfates at the surface. While freeze-thaw is more commonly understood as a mechanism of physical weathering, we suggest that it is a fundamental aspect of chemical weathering on Mars.

Synergistic Effects of Nanoscale CaO2 Combined with PD-1 Inhibitors in the Treatment of Hepatocellular Carcinoma: A Promising Combination.

Purpose: To explore the effect of calcium peroxide nanoparticles (CaO2 NPs) combined with programmed cell death protein 1 (PD-1) inhibitors in the treatment of liver cancer and its related mechanism. Methods: Hepa1-6 cells were cultured to construct the Hepa1-6 mouse liver cancer model. In vivo mechanism study, a unilateral tumor model was established. Eighteen tumor-bearing mice were randomly divided into the control group (intra-tumoral injection of PBS solution) and the experimental group (intra-tumoral injection of CaO2 NPs). A hypoxic probe, pH probe, and micro-CT were used to evaluate the effect of CaO2 NPs on improving hypoxia, neutralizing acidity, and inducing calcium overload within the tumor. To study the effect of CaO2 NPs combined with PD-1 inhibitors on proximal and distal tumors, the bilateral tumor model was established. Forty tumor-bearing mice were randomly divided into the control group (intra-tumoral/intra-peritoneal injection of PBS solution), CaO2 NPs group (intra-tumoral injection of CaO2 NPs), PD-1 group (intra-peritoneal injection of PD-1 inhibitor), and the combination group (intra-tumoral injection of CaO2 NPs and intra-peritoneal injection of PD-1 inhibitors). The administered side was recorded as the proximal tumor. Tumor volume and body weight were measured every 2 days after treatment. On day 8, serum and tumor samples were collected. The immune factors in serum (Interferon-γ (IFN-γ), Tumour necrosis factor-α (TNF-α), Interleukin-2 (IL-2), and Interleukin-10 (IL-10)) and tumor tissue (IFN-γ and TNF-α) were detected by ELISA. H&E staining was used to detect tumor necrosis. Immunohistochemical staining was used to detect the amount of CD4+ and CD8+ T cells within the tumor. By analyzing the tumor volume, pathological indexes, and immune-related indexes, the effects of CaO2 NPs combined with PD-1 inhibitors on proximal and distal tumors were evaluated, and they mediated immunomodulatory effects (including local and systemic immunity), and their effects on tumor burden were studied. In addition, a unilateral tumor model was established to study the effect of CaO2 NPs combined with PD-1 inhibitors on survival time. Results: The results of in vivo mechanism study showed that CaO2 NPs can improve hypoxia, neutralize acidity, and induce calcium overload within tumors. The results of the study on the effect of CaO2 NPs combined with PD-1 inhibitor on proximal and distal tumors showed that, compared with the other three groups, the bilateral tumor burden of the combination group was significantly reduced, the intra-tumoral infiltration of CD8+ and CD4+ T cells were significantly increased, the secretion of anti-tumor immune factors in tumor and serum was increased, and the secretion of pro-tumor immune factors was decreased. Mice in the combination group showed the longest survival compared with the other groups. Conclusion: CaO2 NPs can improve hypoxia, neutralize acidity, and induce calcium overload within tumors, so as to reduce tumor burden and realize an immunosuppressive tumor transformation to a hot tumor, and play a synergistic role with PD-1 inhibitors in anti-liver cancer.

Age, growth, reproduction and mortality of Xenocypris argentea (Günther,1868) in the lower reaches of the Tangwang River, China.

To investigate various population biological parameters of Xenocypris argentea in the lower reaches of the Tangwang River (China), a comprehensive study was conducted for the first time. A total of 1,003 samples were collected from April to November 2022. The collected samples revealed that female X. argentea had total lengths ranging from 12.4 cm to 25.7 cm (weighing 15.86 g to 159.55 g), and male X. argentea had total lengths ranging from 10.8 cm to 23.9 cm (weighing 9.27 g to 121.06 g). The age of the samples was determined using otolith analysis, indicating that the ages ranged from 1 to 5 years old in both females and males. The length-weight relationships were further analyzed, uncovering the allometric growth index (b) was 3.1296 for females, indicating a positive allometric growth pattern. Differently, males exhibited a b value of 3.0274, suggesting an isometric growth pattern. Furthermore, the von Bertalanffy growth formula provided insights into the growth characteristics of X. argentea, revealing an asymptotic total length (L∞) of 36.096 cm and a growth coefficient (K) of 0.121. The analysis of the gonadal somatic index (GSI) and ovarian development period indicated that the spawning period occurred from April to July, with peak spawning in June. The study also explored fecundity-related traits, finding that individual absolute fecundity (FA) ranged from 11,364 eggs to 56,377 eggs, while eviscerated body weight relative fecundity (FW) ranged from 209 eggs/g to 823 eggs/g. The exploitation rate (E) for X. argentea was calculated as 0.574, suggesting that the population of X. argentea has been overexploited. By revealing previously unknown data on the key life history traits of X. argentea, this study has provided valuable insights that are crucial for the development of conservation strategies and policies.