Origin and evolution of intercrystalline brine in the northern Qaidam Basin based on hydrochemistry and stable isotopes

The Kunteyi Basin, located in northern Qaidam, is known as a significant potash ore deposit in China. It is of great significance to study the origin of the potassium-rich intercrystalline brine to support the exploitation of potassium salts. In this study, the major ion concentrations and isotopic ratios (δ2H, δ18O, and δ11B) of intercrystalline brine were used to analyze the evolution of the brine. The results show that the intercrystalline brine has a much higher concentration of total dissolved solids compared with the oil-field brine. Most of the ions are enriched except Ca2+ and Br−. The value of δ2H and δ18O are much negative while the δ11B values are positive. The analysis of CNa/CCl, CBr/CCl, Cl/(Na + K + Mg) and isotopes ratios, indicate that (1) Atmospheric precipitation is the primary source of water in brine; (2) The salinity of the brine is mainly influenced by halite dissolution; (3) The study area was influenced by the deep hydrothermal fluids. The thermal water recharged the Pleistocene layer, reacted with polyhalite, and formed Mg- and K-rich brine. The solution rose along the channel formed by the Shuangqiquan Fault and was supplied to the shallow intercrystalline brine

Structure and Activity of a Selective Antibiofilm Peptide SK-24 Derived from the NMR Structure of Human Cathelicidin LL-37

The deployment of the innate immune system in humans is essential to protect us from infection. Human cathelicidin LL-37 is a linear host defense peptide with both antimicrobial and immune modulatory properties. Despite years of studies of numerous peptides, SK-24, corresponding to the long hydrophobic domain (residues 9–32) in the anionic lipid-bound NMR structure of LL-37, has not been investigated. This study reports the structure and activity of SK-24. Interestingly, SK-24 is entirely helical (~100%) in phosphate buffer (PBS), more than LL-37 (84%), GI-20 (75%), and GF-17 (33%), while RI-10 and 17BIPHE2 are essentially randomly coiled (helix%: 7–10%). These results imply an important role for the additional N-terminal amino acids (likely E16) of SK-24 in stabilizing the helical conformation in PBS. It is proposed herein that SK-24 contains the minimal sequence for effective oligomerization of LL-37. Superior to LL-37 and RI-10, SK-24 shows an antimicrobial activity spectrum comparable to the major antimicrobial peptides GF-17 and GI-20 by targeting bacterial membranes and forming a helical conformation. Like the engineered peptide 17BIPHE2, SK-24 has a stronger antibiofilm activity than LL-37, GI-20, and GF-17. Nevertheless, SK-24 is least hemolytic at 200 µM compared with LL-37 and its other peptides investigated herein. Combined, these results enabled us to appreciate the elegance of the long amphipathic helix SK-24 nature deploys within LL-37 for human antimicrobial defense. SK-24 may be a useful template of therapeutic potentia

Expression and Prognostic Significance of PD-L2 in Diffuse Large B-Cell Lymphoma

Recent studies suggest that programmed death ligand-2 (PD-L2) constitutes an important antitumor immune response. Here, we investigated the relationship between PD-L2 expression and clinicopathological features in diffuse large B-cell lymphoma (DLBCL). Immunohistochemistry showed that positive expression of PD-L2 was observed in 45 of 181 newly diagnosed patients, including 14 cases with expression exclusively on tumor cells (TCs) and 31 cases with the expression on both TCs and immune cells (ICs) in the tumor microenvironment (TME). In 21 recurrent patients, positive expression of PD-L2 was present in six cases, including two cases with expression exclusively on TCs, and four cases with the expression on both TCs and ICs in the TME. Patients with PD-L2 tumor proportion score (TPS) ≥1% exhibited a better ECOG performance status (PS) (ECOG PS score <2, P = 0.041), lower international prognostic index (IPI) score (P < 0.001), and early Ann Arbor stage (Ann Arbor stage I or II, P = 0.010). Similarly, patients with PD-L2 immune proportion score (IPS) ≥1% also exhibited a better ECOG PS (ECOG PS score < 2, P = 0.006) and lower IPI score (P = 0.001). Survival analysis showed that patients with PD-L2 TPS ≥1% exhibited prolonged overall survival (OS) and progression-free survival (PFS). However, survival analysis showed no prognostic significance based on expression of PD-L2 on ICs in the TME. TC PD-L2 expression was significantly associated with OS (P = 0.041) and PFS (P = 0.001). In the multivariate analysis, TC PD-L2 expression was an independent prognostic risk factor for PFS (P = 0.013), but not for OS (P = 0.249). Furthermore, we found that higher TC and IC PD-L2 expression was associated with higher objective response rate (ORR). Moreover, we demonstrated that the expression level of PD-L2 was positively correlated with the expression status of M1 macrophage markers CD86. Our findings highlight PD-L2 as a promising therapeutic target in DLBCL

The economic burden of cervical cancer from diagnosis to one year after final discharge in Henan Province, China: A retrospective case series study.

BACKGROUND: In China, the disease burden of cervical cancer remains substantial. Human papillomavirus (HPV) vaccines are expensive and not yet centrally funded. To inform immunization policy, understanding the economic burden of the disease is necessary. This study adopted a societal perspective and investigated costs and quality of life changes associated with cervical cancer from diagnosis to one year after final discharge in Henan province, China. METHODS: Inpatient records of cervical cancer patients admitted to the largest cancer hospital in Henan province between Jan. 2017 and Dec. 2018 were extracted. A telephone interview with four modules was conducted in Jun.-Jul. 2019 with a 40% random draw of patients to obtain direct non-medical costs and indirect costs associated with inpatients, costs associated with outpatient visits, and changes in quality of life status using the EQ-5D-5L instrument. Direct medical expenditures were converted to opportunity costs of care using cost-to-charge ratios obtained from hospital financial reports. For each clinical stage (IA-IV), total costs per case from diagnosis to one year after final discharge were extrapolated based on inpatient records, responses to the telephone interview, and recommendation on outpatient follow-ups by Chinese cervical cancer treatment guidelines. Loss in quality-adjusted life years was obtained using the 'under the curve' method and regression predictions. RESULTS: A total of 3,506 inpatient records from 1,323 patients were obtained. Among 541 randomly selected patients, 309 completed at least one module of the telephone interview. The average total costs per case associated with cervical cancer from diagnosis to one year after final discharge ranged from $8,066-$22,888 (in 2018 US Dollar) and the quality-adjusted life years loss varied from 0.05-0.26 for IA-IV patients. CONCLUSIONS: The economic burden associated with cervical cancer is substantial in Henan province. Our study provided important baseline information for cost-effectiveness analysis of HPV immunization program in China

Neurological risks of COVID-19 in women: the complex immunology underpinning sex differences

The COVID-19 pandemic has uncovered many mysteries about SARS-CoV-2, including its potential to trigger abnormal autoimmune responses. Emerging evidence suggests women may face higher risks from COVID-induced autoimmunity manifesting as persistent neurological symptoms. Elucidating the mechanisms underlying this female susceptibility is now imperative. We synthesize key insights from existing studies on how COVID-19 infection can lead to immune tolerance loss, enabling autoreactive antibodies and lymphocyte production. These antibodies and lymphocytes infiltrate the central nervous system. Female sex hormones like estrogen and X-chromosome mediated effects likely contribute to dysregulated humoral immunity and cytokine profiles among women, increasing their predisposition. COVID-19 may also disrupt the delicate immunological balance of the female microbiome. These perturbations precipitate damage to neural damage through mechanisms like demyelination, neuroinflammation, and neurodegeneration – consistent with the observed neurological sequelae in women. An intentional focus on elucidating sex differences in COVID-19 pathogenesis is now needed to inform prognosis assessments and tailored interventions for female patients. From clinical monitoring to evaluating emerging immunomodulatory therapies, a nuanced women-centered approach considering the hormonal status and immunobiology will be vital to ensure equitable outcomes. Overall, deeper insights into the apparent female specificity of COVID-induced autoimmunity will accelerate the development of solutions mitigating associated neurological harm