Optimize Vancomycin Dose in Surgical Ward Patients with Augmented Renal Clearance Determined by Chronic Kidney Disease Epidemiology Collaboration Equation.

Background: In the field of postoperative care, infections caused by Gram-positive bacteria pose a major clinical challenge. Vancomycin is a key therapeutic agent whose efficacy is greatly influenced by renal function, particularly by augmented renal clearance (ARC). The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (eGFR) is an easy and commonly used method to predict ARC; however, it is not well studied to determine vancomycin dose. In this study, we examined the effectiveness of the CKD-EPI equation in determining ARC and optimizing the dose of vancomycin for surgical ward patients. Methodology: A retrospective observational study was conducted to examine 158 surgical ward patients receiving vancomycin. Data on demographics, medical history, and vancomycin dosing were collected. Renal function was evaluated using the CKD-EPI equation, with ARC defined as eGFR ≥ 96.5 mL/min/1.73 m2. Vancomycin pharmacokinetics were calculated using the ClinCalc tool. Results: ARC was in 54% of the patients. Compared with patients without ARC, those with ARC were younger and had lower serum creatinine levels. They also required higher vancomycin doses but had lower trough concentrations and 24-hour area-under-the-curve values. A significant correlation was observed between eGFR and vancomycin clearance, with eGFR > 96.5 mL/min/1.73 m2 necessitating higher vancomycin doses (>45 mg/kg/day) to achieve the desired area under the curve to minimum inhibitory concentration ratio. Conclusion: For surgical ward patients with CKD-EPI eGFR ≥ 96.5 mL/min/1.73 m2, a vancomycin dosage of >45 mg/kg/day may be recommended to reach effective therapeutic levels. Overall, this study emphasizes the importance of tailoring vancomycin therapy depending on renal function to ensure efficacy and mitigate the risk of antimicrobial resistance in surgical ward patients.

Gastric Cancer Signaling Pathways and Therapeutic Applications.

Gastric cancer (GC) is a prevalent malignant tumor and ranks as the second leading cause of death among cancer patients worldwide. Due to its hidden nature and difficulty in detection, GC has a high incidence and poor prognosis. Traditional treatment methods such as systemic chemotherapy, radiotherapy, and surgical resection are commonly used, but they often fail to achieve satisfactory curative effects, resulting in a very low 5-year survival rate for GC patients. Currently, targeted therapy and immunotherapy are prominent areas of research both domestically and internationally. These methods hold promise for the treatment of GC. This article focuses on the signaling pathways associated with the development of GC, as well as the recent advancements and applications of targeted therapy and immunotherapy. The aim is to provide fresh insights for the clinical treatment of GC.

ZCCHC8 p.P410A disrupts nucleocytoplasmic localization, promoting idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a special kind of chronic interstitial lung disease with insidious onset. Previous studies have revealed that mutations in ZCCHC8 may lead to IPF. The aim of this study is to explore the ZCCHC8 mutations in Chinese IPF patients. METHODS: Here, we enrolled 124 patients with interstitial lung disease from 2017 to 2023 in our hospital. Whole exome sequencing and Sanger sequencing were employed to explore the genetic lesions of these patients. RESULTS: Among these 124 patients, a novel mutation (NM_017612: c.1228 C > G/p.P410A) of Zinc Finger CCHC-Type Containing 8 (ZCCHC8)was identified in a family with IPF and chronic obstructive lung disease. As a component of the nuclear exosome-targeting complex that regulates the turnover of human telomerase RNA, ZCCHC8 mutations have been reported may lead to IPF in European population and American population. Functional study confirmed that the novel mutation can disrupt the nucleocytoplasmic localization of ZCCHC8, which further decreased the expression of DKC1 and RTEL1, and finally reduced the length of telomere and led to IPF and related disorders. CONCLUSIONS: We may first report the ZCCHC8 mutation in Asian population with IPF. Our study broadens the mutation, phenotype, and population spectrum of ZCCHC8 deficiency.

Tetrahydroberberine Prevents Ovariectomy-Induced Bone Loss by Inhibiting RANKL-Induced Osteoclastogenesis and Promoting Osteoclast Apoptosis.

Postmenopausal osteoporosis (PMOP) arises from the disruption in bone remodeling caused by estrogen deficiency, leading to a heightened susceptibility to osteoporotic fractures in aging women. Tetrahydroberberine (THB) is a chemical compound extracted from Corydalis yanhusuo, a member of the traditional Chinese medicine series "Zhejiang eight taste", possessing a variety of pharmacological functions such as lowering lipids and preventing muscle atrophy. However, the impact of THB on PMOP has not been systematically explored. In vitro experiments supported that THB suppresses osteoclast formation and resorption of bone concentration-dependently. Further experiments confirmed that these inhibitory effects of THB were related to inhibition on expressions of osteoclast-specific genes, the mitogen-activated protein kinase (MAPK) pathway, and the nuclear factor kappa-B (NF-κB) pathway and an increased apoptosis level in mature osteoclasts. Additionally, THB treatment mitigated the ovariectomy-induced bone loss and improved the skeletal microarchitecture in vivo. In conclusion, THB has such potential to improve the PMOP status.

Handling delayed or missed direct oral anticoagulant doses: model-informed individual remedial dosing.

Non-adherence to direct oral anticoagulants (DOACs) pharmacotherapy may increase the risks of thromboembolism or bleeding, and delayed or missed doses are the most common types of non-adherence. Current recommendations from regulatory agencies or guidelines regarding this issue lack evidence and fail to consider individual differences. The study aims to develop individual remedial dosing strategies when the dose was delayed or missed for DOACs including rivaroxaban, apixaban, edoxaban, and dabigatran etexilate. Remedial dosing regimens based on population pharmacokinetic (PK)-pharmacodynamic (PD) modeling and simulation strategies were developed to expeditiously restore drug concentration or PD biomarkers within the therapeutic range. Population PK-PD characteristics of DOACs were retrieved from previously published literature. The effect of factors which influence PK and PD parameters were assessed for their impact on remedial dosing regimens. A web-based dashboard was established with R-shiny to recommend remedial dosing regimens based on patient traits, dosing schedules, and delay duration. Addressing delayed or missed doses relies on the delay time and specific DOACs involved. Additionally, age, body weight, renal function, and polypharmacy may marginally impact remedial strategies. The proposed remedial dosing strategies surpass current recommendations, with less deviation time beyond the therapeutic range. The online dashboard offers quick and convenient solutions for addressing missed or delayed DOACs. We developed a superior, cost-free tool for managing delayed or missed DOACs doses. Individualized remedial dosing strategies could be approached based on patient characteristics to decrease the risks of bleeding and thrombosis.

Effects of epidural anesthesia and analgesia on the incidence of chronic pain after thoracoscopic lung surgery: A retrospective cohort study.

Objective: Chronic postoperative pain (CPSP) is common after thoracic surgery, even after the less invasive video-assisted thoracoscopic surgery (VATS). This study investigated the effect of thoracic epidural anesthesia (TEA) on the development of CPSP. Materials: We retrospectively analyzed the data of patients who underwent VATS at our center between 2020 and 2022. The enrolled patients were divided into the epidural block (EPI) and patient-controlled intravenous analgesia (PCIA) groups. A telephone questionnaire was used to collect information regarding CPSP, which was defined as a numerical rating scale (VAS) score ≥1 at 3 or 6 months postoperatively. Additionally, statistical analyses were performed to identify the risk factors for CPSP in the two groups. Results: Overall, 894 patients completed the follow-up interviews at 3 and 6 months, with 325 and 569 patients in the PCIA and EPI groups, respectively. The incidence rates of CPSP in the PCIA group at 3 and 6 months were 16.9 % (95 % confidence interval [CI]: 9.3-32.7 %) and 13.5 % (95 % CI: 8.7-33.4 %), and 10.3 % (95 % CI: 8.1-30.5 %) and 3.6 % (95 % CI: 3.5-21.5 %) in EPI group, respectively. The incidence of CPSP at 3 months (P = 0.0048) and 6 months (P < 0.005) was statistically significant in both groups. Age and lymph node dissection were significantly associated with CPSP. Conclusions: Compared to PCIA, TEA was associated with a lower incidence of CPSP after VATS, and should be considered an important part of the analgesia regimen for patients with VATS.

Spatiotemporally selective astrocytic ATP dynamics encode injury information sensed by microglia following brain injury in mice.

Injuries to the brain result in tunable cell responses paired with stimulus properties, suggesting the existence of intrinsic processes that encode and transmit injury information; however, the molecular mechanism of injury information encoding is unclear. Here, using ATP fluorescent indicators, we identify injury-evoked spatiotemporally selective ATP dynamics, Inflares, in adult mice of both sexes. Inflares are actively released from astrocytes and act as the internal representations of injury. Inflares encode injury intensity and position at their population level through frequency changes and are further decoded by microglia, driving changes in their activation state. Mismatches between Inflares and injury severity lead to microglia dysfunction and worsening of injury outcome. Blocking Inflares in ischemic stroke in mice reduces secondary damage and improves recovery of function. Our results suggest that astrocytic ATP dynamics encode injury information and are sensed by microglia.

circRNA6448-14/miR-455-3p/OTUB2 axis stimulates glycolysis and stemness of esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a gastrointestinal malignancy with high incidence. This study aimed to reveal the complete circRNA-miRNA-mRNA regulatory network in ESCC and validate its function mechanism. METHOD: Expression of OTU Domain-Containing Ubiquitin Aldehyde-Binding Protein 2 (OTUB2) in ESCC was analyzed by bioinformatics to find the binding sites between circRNA6448-14 and miR-455-3p, as well as miR-455-3p and OTUB2. The binding relationships were verified by RNA Immunoprecipitation (RIP) and dual-luciferase assay. The expressions of circRNA6448-14, miR-455-3p, and OTUB2 were detected by quantitative real-time polymerase chain reaction (qRT-PCR). MTT assay measured cell viability, and the spheroid formation assay assessed the ability of stem cell sphere formation. Western blot (WB) determined the expression of marker proteins of stem cell surface and rate-limiting enzyme of glycolysis. The Seahorse XFe96 extracellular flux analyzer measured the rate of extracellular acidification rate and cellular oxygen consumption. Corresponding assay kits assessed cellular glucose consumption, lactate production, and adenosine triphosphate (ATP) generation. RESULTS: In ESCC, circRNA6448-14 and OTUB2 were highly expressed in contrast to miR-455-3p. Knocking down circRNA6448-14 could prevent the glycolysis and stemness of ESCC cells. Additionally, circRNA6448-14 enhanced the expression of OTUB2 by sponging miR-455-3p. Overexpression of OTUB2 or silencing miR-455-3p reversed the inhibitory effect of knockdown of circRNA6448-14 on ESCC glycolysis and stemness. CONCLUSION: This research demonstrated that the circRNA6448-14/miR-455-3p/OTUB2 axis induced the glycolysis and stemness of ESCC cells. Our study revealed a novel function of circRNA6448-14, which may serve as a potential therapeutic target for ESCC.

Interactions between platelets and the cancer immune microenvironment.

Cancer is a leading cause of death in both China and developed countries due to its high incidence and low cure rate. Immune function is closely linked to the development and progression of tumors. Platelets, which are primarily known for their role in hemostasis, also play a crucial part in the spread and progression of tumors through their interaction with the immune microenvironment. The impact of platelets on tumor growth and metastasis depends on the type of cancer and treatment method used. This article provides an overview of the relationship between platelets and the immune microenvironment, highlighting how platelets can either protect or harm the immune response and cancer immune escape. We also explore the potential of available platelet-targeting strategies for tumor immunotherapy, as well as the promise of new platelet-targeted tumor therapy methods through further research.

Integrated anatomical structure, physiological, and transcriptomic analyses to identify differential cold tolerance responses of Ziziphus jujuba mill. 'Yueguang' and its autotetraploid 'Hongguang'.

Cold stress is a limiting stress factor that limits plant distribution and development; however, polyploid plants have specific characteristics such as higher resistance to abiotic stress, especially cold stress, that allow them to overcome this challenge. The cultivated cultivar Ziziphus jujuba Mill. 'Yueguang' (YG) and its autotetraploid counterpart 'Hongguang' (HG) exhibit differential cold tolerance. However, the underlying molecular mechanism and methods to enhance their cold tolerance remain unknown. Anatomical structure and physiological analysis indicated YG had a higher wood bark ratio, and xylem ratio under cold treatment compared to HG. However, the half-lethal temperature (LT50), cortex ratio, and malondialdehyde (MDA) content were significantly decreased in YG than HG, which indicated YG was cold tolerant than HG. Transcriptome analysis showed that 2084, 1725, 2888, and 2934 differentially expressed genes (DEGs) were identified in HC vs YC, H20 vs Y20, Y20 vs YC, and H20 vs HC treatment, respectively. Meanwhile, KEGG enrichment analysis of DEGs showed that several metabolic pathways, primarily plant hormone signal transduction and the MAPK signaling pathway, were involved in the differential regulation of cold tolerance between YG and HG. Furthermore, exogenous abscisic acid (ABA) and brassinolide (BR) treatments could improve their cold tolerance through increased SOD and POD activities, decreased relative electrical conductivity, and MDA content. All of these findings suggested that plant hormone signal transduction, particularly ABA and BR, might have an important role in the regulation of differential cold tolerance between YG and HG, laying the foundation for further improving cold tolerance in jujube and examining the molecular mechanisms underlying differences in cold tolerance among different ploidy cultivars.

Electropositive Citric Acid-Polyethyleneimine Carbon Dots Carrying the PINK1 Gene Regulate ATP-Related Metabolic Dysfunction in APP/PS1-N2a Cells.

(1) Background: Alzheimer's disease (AD) is characterized by ß-amyloid (Aß) peptide accumulation and mitochondrial dysfunction during the early stage of disease. PINK1 regulates the balance between mitochondrial homeostasis and bioenergy supply and demand via the PINK1/Parkin pathway, Na+/Ca2+ exchange, and other pathways. (2) Methods: In this study, we synthesized positively charged carbon dots (CA-PEI CDs) using citric acid (CA) and polyethyleneimine (PEI) and used them as vectors to express PINK1 genes in the APP/PS1-N2a cell line to determine mitochondrial function, electron transport chain (ETC) activity, and ATP-related metabolomics. (3) Results: Our findings showed that the CA-PEI CDs exhibit the characteristics of photoluminescence, low toxicity, and concentrated DNA. They are ideal biological carriers for gene delivery. PINK1 overexpression significantly increased the mitochondrial membrane potential in APP/PS1-N2a cells and reduced reactive-oxygen-species generation and Aß1-40 and Aß1-42 levels. An increase in the activity of NADH ubiquinone oxidoreductase (complex I, CI) and cytochrome C oxidase (complex IV, CIV) induces the oxidative phosphorylation of mitochondria, increasing ATP generation. (4) Conclusions: These findings indicate that the PINK gene can alleviate AD by increasing bioenergetic metabolism, reducing Aß1-40 and Aß1-42, and increasing ATP production.

Trilaciclib dosage in Chinese patients with extensive-stage small cell lung cancer: a pooled pharmacometrics analysis.

This study aimed to analyze potential ethnic disparities in the dose-exposure-response relationships of trilaciclib, a first-in-class intravenous cyclin-dependent kinase 4/6 inhibitor for treating chemotherapy-induced myelosuppression in patients with extensive-stage small cell lung cancer (ES-SCLC). This investigation focused on characterizing these relationships in both Chinese and non-Chinese patients to further refine the dosing regimen for trilaciclib in Chinese patients with ES-SCLC. Population pharmacokinetic (PopPK) and exposure-response (E-R) analyses were conducted using pooled data from four randomized phase 2/3 trials involving Chinese and non-Chinese patients with ES-SCLC. PopPK analysis revealed that trilaciclib clearance in Chinese patients was approximately 17% higher than that in non-Chinese patients with ES-SCLC. Sex and body surface area influenced trilaciclib pharmacokinetics in both populations but did not exert a significant clinical impact. E-R analysis demonstrated that trilaciclib exposure increased with a dosage escalation from 200 to 280 mg/m2, without notable changes in myeloprotective or antitumor efficacy. However, the incidence of infusion site reactions, headaches, and phlebitis/thrombophlebitis rose with increasing trilaciclib exposure in both Chinese and non-Chinese patients with ES-SCLC. These findings suggest no substantial ethnic disparities in the dose-exposure-response relationship between Chinese and non-Chinese patients. They support the adoption of a 240-mg/m2 intravenous 3-day or 5-day dosing regimen for trilaciclib in Chinese patients with ES-SCLC.

Computation-Guided Rational Design of Cysteine-Less Protein Variants in Engineered hCGL.

The engineered human cystathionine-γ-lyase (hCGL) resulting in enhanced activity toward both cysteine and cystine unveils a potential robust antitumor activity. However, the presence of cysteine residues has the potential to induce oligomerization or incorrect disulfide bonding, which may decrease the bioavailability of biopharmaceuticals. Through a meticulous design process targeting the cysteine residues within engineered hCGL, a set of potential beneficial mutants were obtained by virtual screening employing Rosetta and ABACUS. Experimental measurements have revealed that most of the mutants showed increased activity toward both substrates l-Cys and CSSC. Furthermore, mutants C109V and C229D demonstrated Tm value increases of 8.2 and 1.8 °C, respectively. After an 80 min incubation at 60 °C, mutant C229D still maintained high residual activity. Unexpectedly, mutant C109V, displaying activity approximately 2-fold higher than the activity of wild type (WT) for both substrates, showed disappointing instability in plasma, which suggests that computational design still requires further consideration. Analysis of their structure and molecular dynamics (MD) simulation revealed the impact of hydrophobic interaction, hydrogen bonds, and near-attack conformation (NAC) stability on activity and stability. This study acquired information about mutants that exhibit enhanced activity or thermal resistance and serve as valuable guidance for subsequent specific cysteine modifications.

Magnetic Resonance-Guided Focused Ultrasound for Treatment of Essential Tremor: Ventral Intermediate Nucleus Ablation Alone or Additional Posterior Subthalamic Area Lesioning?

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) for treatment of essential tremor (ET) traditionally targets the ventral intermediate (Vim) nucleus. Recent strategies include a secondary lesion to the posterior subthalamic area (PSA). OBJECTIVE: The aim was to compare lesion characteristics, tremor improvement, and adverse events (AE) between patients in whom satisfactory tremor suppression was achieved with lesioning of the Vim alone and patients who required additional lesioning of the PSA. METHODS: Retrospective analysis of data collected from ET patients treated with MRgFUS at St Vincent's Hospital Sydney was performed. Clinical Rating Scale for Tremor (CRST), hand tremor score (HTS), and Quality of Life in Essential Tremor Questionnaire (QUEST) were collected pre- and posttreatment in addition to the prevalence of AEs. The lesion coordinates and overlap with the dentatorubrothalamic tract (DRTT) were evaluated using magnetic resonance imaging. RESULTS: Twenty-one patients were treated in Vim only, and 14 were treated with dual Vim-PSA lesions. Clinical data were available for 29 of the 35 patients (19 single target and 10 dual target). At follow-up (mean: 18.80 months) HTS, CRST, and QUEST in single-target patients improved by 57.97% (P < 0.001), 36.71% (P < 0.001), and 58.26% (P < 0.001), whereas dual-target patients improved by 68.34% (P < 0.001), 35.37% (P < 0.003), and 46.97% (P < 0.005), respectively. The Vim lesion of dual-target patients was further anterior relative to the posterior commissure (PC) (7.84 mm), compared with single-target patients (6.92 mm), with less DRTT involvement (14.85% vs. 23.21%). Dual-target patients exhibited a greater proportion of patients with acute motor AEs (100% vs. 58%); however, motor AE prevalence was similar in both groups at long-term follow-up (33% vs. 38%). CONCLUSION: Posterior placement of lesions targeting the Vim may confer greater tremor suppression. The addition of a PSA lesion, in patients with inadequate tremor control despite Vim lesioning, had a trend toward better long-term tremor suppression; however, this approach was associated with greater prevalence of gait disturbance in the short term.

Development and Evaluation of a Quantitative Systems Pharmacology Model for Mechanism Interpretation and Efficacy Prediction of Atezolizumab in Combination with Carboplatin and Nab-Paclitaxel in Patients with Non-Small-Cell Lung Cancer.

Immunotherapy has shown clinical benefit in patients with non-small-cell lung cancer (NSCLC). Due to the limited response of monotherapy, combining immune checkpoint inhibitors (ICIs) and chemotherapy is considered a treatment option for advanced NSCLC. However, the mechanism of combined therapy and the potential patient population that could benefit from combined therapy remain undetermined. Here, we developed an NSCLC model based on the published quantitative systems pharmacology (QSP)-immuno-oncology platform by making necessary adjustments. After calibration and validation, the established QSP model could adequately characterise the biological mechanisms of action of the triple combination of atezolizumab, nab-paclitaxel, and carboplatin in patients with NSCLC, and identify predictive biomarkers for precision dosing. The established model could efficiently characterise the objective response rate and duration of response of the IMpower131 trial, reproducing the efficacy of alternative dosing. Furthermore, CD8+ and CD4+ T cell densities in tumours were found to be significantly related to the response status. This significant extension of the QSP model not only broadens its applicability but also more accurately reflects real-world clinical settings. Importantly, it positions the model as a critical foundation for model-informed drug development and the customisation of treatment plans, especially in the context of combining single-agent ICIs with platinum-doublet chemotherapy.

Global burden of pancreatic cancer attributable to metabolic risks from 1990 to 2019, with projections of mortality to 2030.

OBJECTIVE: Metabolic risks play a key role in the progression of pancreatic cancer. This study aimed to present global, regional and national data on mortality and disability-adjusted life-year (DALY) for pancreatic cancer attributable to metabolic risk and to forecast mortality to 2030 using data from the Global Burden of Disease (GBD). METHODS: Data on mortality and DALYs due to pancreatic cancer attributable to metabolic risks were obtained from GBD 2019. Metabolic risks include high fasting plasma glucose (FPG) and high body mass index (BMI). Total numbers and age-standardized rates per 100,000 people for mortality and DALYs were reported by age, sex, region and country/territory from 1990 to 2019. The "Bayes age-period-cohort" method was used for projections of mortality to 2030. RESULTS: Globally, there was a 3.5-fold increase in the number of pancreatic cancer deaths attributable to metabolic risk, from 22,091 in 1990 to 77,215 in 2019. High-income North America and Central Europe had the highest age-standardized mortality rates (ASMRs) of pancreatic cancer attributable to high FPG and high BMI in 2019, respectively. From 1990 to 2019, the global ASMR of pancreatic cancer attributable to high FPG and high BMI increased. Countries with high healthcare access quality had much higher age-standardized DALY rates. In the next 10 years, the ASMR of pancreatic cancer attributable to high FPG and high BMI will continue to increase. CONCLUSION: Pancreatic cancer mortality and DALYs attributable to metabolic factors remain high, particularly in high-income regions or countries. Studies on the metabolic mechanism of pancreatic cancer and effective treatment strategies are needed.

A system review of central nervous system tumors on children in China: epidemiology and clinical characteristics.

BACKGROUND: Central nervous system (CNS) tumors are the most common solid tumors in children and the leading cause of cancer-related death in the latter. Currently, the incidence rate exceeds that of leukemia and ranks first in the incidence of malignant tumors in children. METHODS: The epidemiological data on childhood CNS tumors were collected from the Chinese Cancer Registry Annual Report. The annual percent change (APC) of incidence and mortality-rate changes were estimated via Joinpoint regression. Due to a lack of pertinent data, we performed a system review on the clinical-pathological characteristics in Chinese publications. RESULTS: There was no significant increase in the incidence rate (APC: -0.1, 95% CI: -1.5 to 1.3), but there was a significant increase in the mortality rate (APC: 1.8, 95% CI: 0.3 to 3.4) for childhood CNS tumors. In the subgroup analysis, there were significant increases in both the incidence and mortality rates in rural areas (APC in the incidence: 6.2, 95% CI: 2.4 to 10.2; APC in mortality: 4.4, 95% CI: 0.4 to 8.4). The most common location and type of childhood CNS were, respectively, the cerebral hemisphere (25.5%, 95% CI: 21.7% to 29.4%) and astrocytomas (26.8%, 95% CI: 23.9% to 29.6%). CONCLUSIONS: The epidemiological trends, and the relevant prediction, highlighted the need to pay continual attention to childhood CNS tumors, and the clinicopathology evinced its own distinctive characteristics. Timely detection and effective treatment must be further promoted regarding childhood CNS tumors with a view to decreasing the disease burden, especially in rural areas.

Polydopamine Nanostructure-Enhanced Water Interaction with pH-Responsive Manganese Sulfide Nanoclusters for Tumor Magnetic Resonance Contrast Enhancement and Synergistic Ferroptosis-Photothermal Therapy.

Rational structure design benefits the development of efficient nanoplatforms for tumor theranostic application. In this work, a multifunctional polydopamine (PDA)-coated manganese sulfide (MnS) nanocluster was prepared. The polyhydroxy structure of PDA enhanced the water interaction with pH-responsive MnS nanoclusters via hydrogen bonds. At pH 5.5 conditions, the spin-lattice relaxation rate of MnS nanoclusters dramatically increased from 5.76 to 19.33 mM-1·s-1 after the PDA coating, which can be beneficial for efficient tumor magnetic resonance imaging. In addition, PDA endowed MnS nanoclusters with excellent biocompatibility and good photothermal conversion efficiency, which can be used for efficient tumor photothermal therapy (PTT). Furthermore, MnS nanoclusters possess the ability to release H2S in the acidic tumor microenvironment, effectively inhibiting mitochondrial respiration and adenosine triphosphate production. As a result, the expression of heat shock protein was obviously reduced, which can reduce the resistance of tumor cells to photothermal stimulation and enhance the efficacy of PTT. The released Mn2+ also displayed efficient peroxidase and glutathione oxidase-like activity, effectively inducing tumor cell ferroptosis and apoptosis at the same time. Therefore, this nanoplatform could be a potential nanotheranostic for magnetic resonance contrast enhancement and synergistic ferroptosis-PTT of tumors.