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Of concern is a problem of strain gradient porous elastic theory with nonlinear damping terms, whose constitutive equations contain higher-order derivatives of the displacement in the basic postulates. The paper is based on the theory of 'consistency' due to Aouadi et al. [J. Therm. Stress. 43(2)(2020), 191–209] and Ieşan [American Institute of Physics, Conference Proceedings, 1329 (2011), 130–149], and contains four results. We firstly show that the system is global well posed by using maximal monotone operator. The second main result is the existence of global attractors which is proved by the method developed by Chueshov and Lasiecka [Long-time behavior of second order evolution equations with nonlinear damping. Mem. Amer. Math. Soc. vol. 195, no. 912, Providence, 2008; Von Karman evolution equations: well-posedness and long-time dynamics. Springer Monographs in Mathematics, Springer, New York, 2010]. By showing the system is gradient and asymptotically smooth, we establish the existence of global attractors with finite fractal dimension via a stabilizability inequality. Then we study the continuity of global attractors regarding the parameter in a residual dense set. The above results allow the damping terms with polynomial growth. Finally we discuss the exponential decay and global boundedness to the linear case of damping terms of the system. The assumption of equal-speed wave propagations is not needed for all of results obtained. [ABSTRACT FROM AUTHOR]

The problem of Reissner–Mindlin–Timoshenko plate systems with nonlinear damping terms is considered. The main result is the existence of global attractors. By showing the system is gradient and asymptotic smoothness via a stabilizability inequality, we establish the existence of global attractors with finite fractal dimension. The continuity of global attractors regarding the parameter in a residual dense set is also proved. The above results allow the damping terms with polynomial growth. [ABSTRACT FROM AUTHOR]

Saline-alkali land is an important cultivated land reserve resource for tackling global climate change and ensuring food security, partly because it can store large amounts of carbon (C). However, it is unclear how saline-alkali land reclamation (converting saline-alkali land into cultivated land) affects soil C storage. We collected 189 adjacent pairs of salt-affected and cultivated soil samples (0-30 cm deep) from the Songnen Plain, eastern coastal area, Hetao Plain, and northwestern arid area in China. Various soil properties, the soil inorganic C (SIC), organic C (SOC), particulate organic C (POC), and mineral-associated organic C (MAOC) densities, and plant- and microbial-derived C accumulation were determined. Saline-alkali land reclamation inconsistently affected the SIC density but significantly (P < 0.001) increased the SOC density. The SOC, POC, and MAOC densities were predicted well by the integrative soil amelioration index. Saline-alkali land reclamation significantly increased plant-derived C accumulation and the plant-derived C to microbial-derived C ratios in all saline-alkali areas, and less microbial transformation of plant-derived C (i.e., less lignin degradation or oxidation) occurred in cultivated soils than salt-affected soils. The results indicated that saline-alkali land reclamation leads to plant-derived C becoming the dominant contributor of SOC storage. POC storage and MAOC storage were strongly linked to plant- and microbial-derived C accumulation, respectively, caused by saline-alkali land reclamation. Our findings suggest that saline-alkali land reclamation increases C storage in topsoil by preferentially promoting plant-derived C accumulation., (Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved.)

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a rare subtype of inflammatory myofibroblastic tumor, characterized to be an aggressive disease with high frequency of ALK rearrangement, rapid recurrence, and poor prognosis. Primary EIMS of thoracic origin is rarely observed. Herein, we described a case of 28-year-old female developed primary EIMS in the anterior mediastinum with hepatic metastasis. The EIMS displayed sheet-like growth of epithelioid and spindle cells with enlarged nuclei, abundant and eosinophilic cytoplasm, and infiltration of inflammatory cells. Immunohistochemical staining revealed positive expression of ALK in the nuclear membrane, and ALK rearrangement was identified by polymerase chain reaction assay. Alectinib showed partial response, and achieved a meaningful survival benefit for four months. Based on this case report and literature review, ALK inhibitor reveals promising activity on the rare but aggressive EIMS. Awareness of EIMS in thoracic disease and its clinicopathological features is essential to avoid erroneous diagnosis., (© 2024. The Author(s).)

The photoelectron spectra of cluster anions of superoxide (O 2 - ) solvated by one molecule of benzoxazole (BzOx) reveal two competing photodetachment mechanisms: a direct photoemission from the solvated cluster core and an indirect pathway involving temporary anion states of benzoxazole accessed via the O 2 - ·BzOx → O 2 ·BzOx - charge-transfer transitions. Benzoxazole is a bicyclic unsaturated organic molecule that does not form permanent anions. However, its low-lying vacant π* orbitals permit a resonant capture of the electron emitted from the O 2 ) at 0.891 eV and resonance B (π - cluster core. The non-Hermitian theory using a complex absorbing potential predicts the existence of two BzOx - π* resonances within the experimental energy range: resonance A (π 1 * ) at 0.891 eV and resonance B (π 2 * ) at 1.76 eV, relative to the onset of the BzOx + e - continuum at the ground-state geometry of neutral BzOx. Within the clusters, the O 2 ·BzOx - charge-transfer states are partially stabilized relative to the free-electron limit by interactions with the O 2 molecule. These interactions depend on the electronic states of both species. The theory predicts that at the O 2 - ·BzOx cluster geometry, the O 2 ( X 3 Σ g - )·BzOx - (B) resonance is found 1.43 eV (vertically) above O 2 ( a 1 Δ g )·BzOx - (A) states lie at 0.56 and 0.47 eV (vertically) above the respective neutral states. The O 2 ( 3 Σ g - )·BzOx - (B) resonance is found 1.43 eV (vertically) above O 2 ( X 3 Σ g - )·BzOx. Intense signatures of both BzOx - (B) are observed in the 355 nm (3.495 eV) and 532 nm (2.330 eV) photoelectron spectra of the O 2 ( X 3 Σ g - )·BzOx - (A), O 2 ( a 1 Δ g )·BzOx - (A), and O 2 ( 3 Σ g - )·BzOx - (B) are observed in the 355 nm (3.495 eV) and 532 nm (2.330 eV) photoelectron spectra of the O 2 - ·BzOx cluster anion.

Due to the high charge separation efficiency leading to high photocatalytic activity, there has been significant interest in enhancing the charge separation ability of photocatalysts by controlling the heterojunction structure. To investigate the effect of the heterojunction structure on the photocatalytic performance of composite catalysts and understand its corresponding mechanism, a Z-scheme ZnFe 2 O 4 /ZnO/CdS heterojunction was constructed using the ultrasound method and used for CO 2 photoreduction. The Z-scheme heterojunction catalyst demonstrates elevated photocatalytic and charge separation efficiencies. Specifically, the conversion rate for the photocatalytic conversion of CO 2 to CH 4 reaches 105.9 μmol g -1 h -1 , surpassing that of the majority of previously reported semiconductor photocatalysts like ZnFe 2 O 4 /CdS. This research offers a fresh perspective on the development of innovative heterojunction photocatalysts and broadens the utilization of ternary composite materials in CO 2 photoreduction.

Despite a high response rate in chimeric antigen receptor (CAR) T cell therapy for acute lymphocytic leukaemia (ALL) 1-3 , approximately 50% of patients relapse within the first year 4-6 , representing an urgent question to address in the next stage of cellular immunotherapy. Here, to investigate the molecular determinants of ultralong CAR T cell persistence, we obtained a single-cell multi-omics atlas from 695,819 pre-infusion CAR T cells at the basal level or after CAR-specific stimulation from 82 paediatric patients with ALL enrolled in the first two CAR T ALL clinical trials and 6 healthy donors. We identified that elevated type 2 functionality in CAR T infusion products is significantly associated with patients maintaining a median B cell aplasia duration of 8.4 years. Analysis of ligand-receptor interactions revealed that type 2 cells regulate a dysfunctional subset to maintain whole-population homeostasis, and the addition of IL-4 during antigen-specific activation alleviates CAR T cell dysfunction while enhancing fitness at both transcriptomic and epigenomic levels. Serial proteomic profiling of sera after treatment revealed a higher level of circulating type 2 cytokines in 5-year or 8-year relapse-free responders. In a leukaemic mouse model, type 2 high CAR T cell products demonstrated superior expansion and antitumour activity, particularly after leukaemia rechallenge. Restoring antitumour efficacy in type 2 low CAR T cells was attainable by enhancing their type 2 functionality, either through incorporating IL-4 into the manufacturing process or by priming manufactured CAR T products with IL-4 before infusion. Our findings provide insights into the mediators of durable CAR T therapy response and suggest potential therapeutic strategies to sustain long-term remission by boosting type 2 functionality in CAR T cells., (© 2024. The Author(s).)

Current cancer immunotherapy predominately focuses on eliciting type 1 immune responses fighting cancer; however, long-term complete remission remains uncommon 1,2 . A pivotal question arises as to whether type 2 immunity can be orchestrated alongside type 1-centric immunotherapy to achieve enduring response against cancer 3,4 . Here we show that an interleukin-4 fusion protein (Fc-IL-4), a typical type 2 cytokine, directly acts on CD8 + T cells and enriches functional terminally exhausted CD8 + T (CD8 + T TE ) cells in the tumour. Consequently, Fc-IL-4 enhances antitumour efficacy of type 1 immunity-centric adoptive T cell transfer or immune checkpoint blockade therapies and induces durable remission across several syngeneic and xenograft tumour models. Mechanistically, we discovered that Fc-IL-4 signals through both signal transducer and activator of transcription 6 (STAT6) and mammalian target of rapamycin (mTOR) pathways, augmenting the glycolytic metabolism and the nicotinamide adenine dinucleotide (NAD) concentration of CD8 + T TE cells in a lactate dehydrogenase A-dependent manner. The metabolic modulation mediated by Fc-IL-4 is indispensable for reinvigorating intratumoural CD8 + T TE cells. These findings underscore Fc-IL-4 as a potent type 2 cytokine-based immunotherapy that synergizes effectively with type 1 immunity to elicit long-lasting responses against cancer. Our study not only sheds light on the synergy between these two types of immune responses, but also unveils an innovative strategy for advancing next-generation cancer immunotherapy by integrating type 2 immune factors., (© 2024. The Author(s).)

Metamaterial has been captivated a popular notion, offering photonic functionalities beyond the capabilities of natural materials. Its desirable functionality primarily relies on well-controlled conditions such as structural resonance, dispersion, geometry, filling fraction, external actuation, etc. However, its fundamental building blocks-meta-atoms-still rely on naturally occurring substances. Here, we propose and validate the concept of gradient and reversible atomic-engineered metamaterials (GRAM), which represents a platform for continuously tunable solid metaphotonics by atomic manipulation. GRAM consists of an atomic heterogenous interface of amorphous host and noble metals at the bottom, and the top interface was designed to facilitate the reversible movement of foreign atoms. Continuous and reversible changes in GRAM's refractive index and atomic structures are observed in the presence of a thermal field. We achieve multiple optical states of GRAM at varying temperature and time and demonstrate GRAM-based tunable nanophotonic devices in the visible spectrum. Further, high-efficiency and programmable laser raster-scanning patterns can be locally controlled by adjusting power and speed, without any mask-assisted or complex nanofabrication. Our approach casts a distinct, multilevel, and reversible postfabrication recipe to modify a solid material's properties at the atomic scale, opening avenues for optical materials engineering, information storage, display, and encryption, as well as advanced thermal optics and photonics., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Some clinicopathological risk stratification systems (CRSSs) such as the leibovich score have been used to predict the postoperative prognosis of patients with clear cell renal cell carcinoma (ccRCC), but there are no reliable noninvasive preoperative indicators for predicting postoperative prognosis in clinical practice., Purpose: To assess the value of a deep learning (DL) model based on CT images in predicting the postoperative prognosis of patients with ccRCC., Materials and Methods: A total of 382 patients with ccRCC were retrospectively enrolled andallocated to training (n = 229) or testing (n = 153) cohorts at a 6:4 ratio. The features were extracted from precontrast-phase (PCP), corticomedullary-phase (CMP) and nephrographic-phase (NP) CT images with ResNet50, and then extreme learning machines (ELMs) were used to construct classification models. The DL model and Leibovich score were compared and combined. A receiver operating characteristic (ROC) curve and integrated discrimination improvement (IDI) were used to evaluate model performance., Results: Compared with other single-phase DL models, the three-phase CT-based DL model achieved the best performance, with an area under the curve (AUC) of 0.839. Combining the three-phase DL model and the Leibovich score (AUC = 0.823) into a nomogram (AUC = 0.888) statistically improved performance (IDI Nomogram vs. Three-phase = 0.1358, IDI Nomogram vs. Leibovich = 0.1393, [Formula: see text]< 0.001)., Conclusion: The CT-based DL model could be valuable for preoperatively predicting the prognosis of patients with ccRCC, and combining it with the Leibovich score can further improve its predictive performance., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Climate change can pose a significant threat to terrestrial ecosystems by disrupting the circulation of soil nitrogen. However, experimental analyses on the effect of climate change on soil nitrogen cycles and the implications for the conservation of key wildlife species (i.e., the giant panda, Ailuropoda melanoleuca) remain understudied. We investigated the effects of a 1.5 °C, 3 °C, and 4.5 °C temperature increase on nitrogen distribution in different soil layers of bamboo forest via an in-situ experiment and assessed the implications for the growth and survival of arrow bamboo (Bashania faberi), a critical food resource for giant pandas. Our results showed that warming treatments generally increased soil N content, while effects differed between surface soil and subsurface soil and at different warming treatments. Particularly an increase of 1.5 °C raised the subsurface soil NO 3 -N content, as well as the content of N in bamboo leaves. We found a significant positive correlation between the subsurface soil NO 3 -N content and the N content of arrow bamboo. An increase of 3-4.5 °C raised the content of total N and NO 3 -N in the surface soil and led to a reduction in the total aboveground biomass and survival rate of arrow bamboo. Limited warming (e.g., the increase of 0-1.5 °C) may promote the soil N cycle, raise the N-acetylglucosaminidase (NAG) enzyme activity, increase NO 3 -N in subsurface soil, increase the N content of bamboo, and boost the biomass of bamboo - all of which could be beneficial to giant panda survival. However, higher warming (e.g., an increase of 3-4.5 °C) resulted in mass death of bamboo and a large reduction in aboveground biomass. Our findings provide a cautiously optimistic scenario for bamboo forest ecosystems under low levels of warming over a short period of time, but risks from higher levels of warming may be serious, especially considering the unpredictability of global climatic change., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Intraosseous regional administration (IORA) as a widely applicable and clinically valuable route of administration has gained significant attention in the context of total knee arthroplasty (TKA) for the prophylactic administration of antibiotics. However, there is still controversy regarding its effectiveness and safety. The latest meta-analysis reports that the use of IORA for antibiotics in TKA is as safe and effective as IV administration in preventing prosthetic joint infection (PJI), but they did not separate the statistics for primary TKA and revision TKA, which may be inappropriate. There is currently a lack of evidence specifically comparing the outcomes of prophylactic antibiotic administration via IORA or IV route in primary/revision TKA, respectively, and new research evidence has emerged., Purposes: In this study, we conducted a systematic review and meta-analysis with the primary objective of comparing the local drug tissue concentration and the incidence of PJI between preoperative IORA and intravenous (IV) administration of prophylactic antibiotics in TKA. Additionally, the occurrence of complications between the two administration routes was also compared., Patients and Methods: This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement (PRISMA) guidelines. Retrospective cohort studies and prospective randomized controlled trials that utilized intraosseous local drug delivery for prophylactic antibiotics in knee arthroplasty were included. English literature from PubMed, Embase, and Cochrane Library databases was searched from the inception of each database until December 2023. Two researchers independently screened the literature, assessed the quality, and extracted data according to the inclusion criteria. The primary outcomes were local antibiotic tissue concentration and postoperative PJI incidence, while the secondary outcome was the occurrence of postoperative complications. Statistical analysis was performed using Review Manager 5.3 software., Results: This study included 7 prospective randomized controlled trials and 5 retrospective cohort studies. A total of 4091 patients participated in the 12 included studies, with 1,801 cases receiving IORA and 2,290 cases in the control group. In terms of local drug tissue concentration, intraosseous infusion (IO) 500 mg vancomycin significantly increased the drug concentration in the periarticular adipose tissue (SMD: 1.36; 95% CI: 0.87-1.84; P < 0.001; I 2  = 0%) and bone tissue (SMD: 0.94; 95% CI: 0.49-1.40; P < 0.001; I 2  = 0%) compared to IV 1 g vancomycin. Regarding the incidence of postoperative PJI after primary TKA, IO 500 mg vancomycin was more effective in reducing the occurrence of PJI compared to IV 1 g vancomycin (OR: 0.19; 95% CI: 0.06-0.59; P < 0.001; I 2  = 36%). Finally, no significant differences were found between the two groups in terms of postoperative pulmonary embolism (PE) (OR: 1.72; 95% CI: 0.22-13.69; P = 0.59; I 2  = 0%) and vancomycin-related complications (OR: 0.54; 95% CI: 0.25-1.19; P = 0.44; I 2  = 0%)., Conclusions: Preoperative prophylactic antibiotic administration via IORA in TKA significantly increases local drug tissue concentration without significantly increasing systemic drug-related complications compared to traditional IV administration. In primary TKA, low-dose vancomycin via IORA is more effective in reducing the incidence of PJI compared to traditional IV regimens. However, its effectiveness remains controversial in high-risk populations for PJI, such as obese, diabetic, and renal insufficiency patients, as well as in revision TKA., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Poly(ADP-ribose) polymerase 1 (PARP1) inhibitors have revolutionized the treatment of many cancers with DNA-repairing deficiencies via synthetic lethality. Advocated by the polypharmacology concept, recent evidence discovered that a significantly synergistic effect in increasing the death of cancer cells was observed by simultaneously perturbating the enzymatic activities of bromodomain-containing protein 4 (BRD4) and PARP1. Here, we developed a novel cheminformatics approach combined with a structure-based method aiming to facilitate the design of dual PARP1-BRD4 inhibitors. Instead of linking pharmacophores, the developed approach first identified merged pharmacophores (a pool of amide-containing ring systems), from which phenanthridin-6(5 H )-one was further prioritized. Based on this starting point, several small molecules were rationally designed, among which HF4 exhibited low micromolar inhibitory activity against BRD4 and PARP1, particularly exhibiting strong inhibition of BRD4 BD1 with an IC 50 value of 204 nM. Furthermore, it demonstrated potent antiproliferative effects against breast cancer gene-deficient and proficient breast cancer cell lines by arresting cell cycle progression and impeding DNA damage repair. Collectively, our systematic efforts to design lead-like molecules have the potential to open doors for the exploration of dual PARP1-BRD4 inhibitors as a promising avenue for breast cancer treatment. Furthermore, the developed approach can be extended to systematically design inhibitors targeting PARP1 and other related targets.

Background: Abnormal arachidonic acid metabolism in the tumor microenvironment is closely related to cancer progression; however, thyroid cancer was rarely researched., Methods: Through lipidomic analysis, we disclosed that dysregulated arachidonic acid metabolism plays dual effects on thyroid cancer. The promoting role of arachidonic acid in the progression of thyroid cancer cells was evaluated utilizing cell viability (CCK-8 assay) and transwell invasion assays, confirmed by corresponding inhibitors. Lipid peroxidation and the use of various cell death inhibitors confirmed that arachidonic acid confers vulnerability to ferroptosis in thyroid cancer. The roles of arachidonic acid and ferroptosis inducer in thyroid cancer were assessed in a xenograft mouse model., Results: On one hand, arachidonic acid promotes the progression of thyroid cancer through the cyclooxygenase/prostaglandin pathway; on another hand, arachidonic acid confers vulnerability to ferroptosis through lipoxygenases. Moreover, iPLA2β drives converse roles of arachidonic acid between cancer-progression and ferroptosis vulnerability through releasing free arachidonic acid from the cell membrane. Finally, we confirmed high arachidonic acid diet promotes the development of thyroid cancer in vivo, whereas ferroptosis inducer sulfasalazine dramatically reduced tumor growth of mice with feeding arachidonic acid., Conclusions: Our research demonstrated the roles of iPLA2β in conversing dual effects of arachidonic acid in thyroid cancer and provides ferroptosis inducer as a potential therapeutic strategy., (© 2024 Wiley Periodicals LLC.)

Background: Chronic inflammation plays a crucial role in the pathogenesis of overweight/obesity. Nuclear receptor subfamily 2, group E, member 1 (NR2E1) is one of the nuclear receptor family proteins that play crucial roles in regulating numerous life processes. In this study, we attempted to detect NR2E1 levels in peripheral blood mononuclear cells (PBMCs) of overweight/obese people and preliminarily elucidate the regulatory role of NR2E1 in obesity-related chronic inflammation., Methods: We conducted a cross-sectional analysis of the clinical and biochemical data from 62 overweight/obese people and 70 control subjects. PBMCs of the participants were collected for detection of NR2E1 levels. PBMCs isolated from the control subjects were treated with different concentrations of palmitic acid (PA). We also transfected p-EGFP-N1-NR2E1 plasmids into PBMCs and treated them with PA, then detected TNF-α and IL-6 concentrations in the supernatant of PBMCs., Results: The NR2E1 mRNA and protein levels in overweight/obese people were both significantly higher than those in normal-BMI people (p < 0.01). NR2E1 mRNA levels in PBMCs of overweight/obese people were positively related with TC, FFA, IL-6, TNF-α (r = 0.387, 0.440, 0.610, 0.530, p < 0.01) and LDL-c (r = 0.290, p < 0.05). A similar correlation was also found between NR2E1 protein levels and these parameters. The expression of NR2E1 in PBMCs from the control subjects increased apparently with the treatment of PA in a concentration-depend manner in vitro . Overexpression of NR2E1 in PBMCs decreased TNF-α and IL-6 expression induced by PA (p < 0.01)., Conclusion: NR2E1 levels are increased in overweight/obese people and have a positive relationship with TC, FFA, LDL-C, TNF-α and IL-6. Overexpression of NR2E1 could alleviate PA-induced chronic inflammation. NR2E1 may be a potential target for regulating chronic inflammation in obesity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

The influence of transporters on the pharmacokinetics of drugs is being increasingly recognized, and drug-drug interactions (DDIs) via modulation of transporters could lead to clinical adverse events. Organic anion-transporting polypeptide 1B (OATP1B) is a liver-specific uptake transporter in humans that can transport a broad range of substrates, including statins. It is a challenge to predict OATP1B-mediated DDIs using preclinical animal models because of species differences in substrate specificity and abundance levels of transporters. PXB-mice are chimeric mice with humanized livers that are highly repopulated with human hepatocytes and have been widely used for drug metabolism and pharmacokinetics studies in drug discovery. In the present study, we measured the exposure increases [blood AUC (area under the blood/plasma concentration-time curve) and C max ] of 10 OATP1B substrates in PXB-mice upon coadministration with rifampin, a potent OATP1B specific inhibitor. These data in PXB-mice were then compared with the observed DDIs between OATP1B substrates and single-dose rifampin in humans. Our findings suggest that the DDIs between OATP1B substrates and rifampin in PXB-mouse are comparable with the observed DDIs in the clinic. Since most OATP1B substrates are metabolized by cytochromes P450 (CYPs) and/or are substrates of P-glycoprotein (P-gp), we further validated the utility of PXB-mice to predict complex DDIs involving inhibition of OATP1B, CYPs, and P-gp using cyclosporin A (CsA) and gemfibrozil as perpetrators. Overall, the data support that the chimeric mice with humanized livers could be a useful tool for the prediction of hepatic OATP1B-mediated DDIs in humans. SIGNIFICANCE STATEMENT: The ability of PXB-mouse with humanized liver to predict organic anion-transporting polypeptide 1B (OATP1B)-mediated drug-drug interactions (DDIs) in humans was evaluated. The blood exposure increases of 10 OATP1B substrates with rifampin, an OATP1B inhibitor, in PXB-mice have a good correlation with those observed in humans. More importantly, PXB-mice can predict complex DDIs, including inhibition of OATP1B, cytochromes P450 (CYPs), and P-glycoprotein (P-gp) in humans. PXB-mice are a promising useful tool to assess OATP1B-mediated clinical DDIs., (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.)

Laccases are the most commonly used agents for the treatment of phenolic pollutants. To address the instability and high cost of natural laccases, we investigated nucleobase-modulated copper nanomaterial with laccase-like activity. Various nucleobases, including adenine, guanine, cytosine, and thymine, were investigated as templates for Cu 2+ reduction and copper nanomaterials formation due to their coordination capacity. By comparing structure and catalytic activity, the cytosine-mediated copper nanomaterial (C-Cu) had the best laccase-like activity and other nucleobase-templated copper nanomaterials exhibited low catalytic activity under the same conditions. The mechanism of nucleobase regulation of the catalytic activity of copper nanomaterials was further analyzed using X-ray photoelectron spectroscopy and density functional theory. The possible catalytic mechanisms of C-Cu, including substrate adsorption, substrate oxidation, oxygen binding, and oxygen reduction, were proposed. Remarkably, nucleobase-modulated copper nanozymes showed high stability and catalytic oxidation performance at various pH values, temperatures, long-term storage, and high salinity. In combination with electrochemical techniques, a portable electrochemical sensor for measuring phenolic pollutants was developed. This novel sensor exhibited a good linear response to catechol (10-1000 μM) with a limit of detection of 1.8 μM and excellent selectivity and anti-interference ability. This study provides not only a new strategy for the regulation of the laccase-like activity of copper nanomaterials but also a novel tool for the effective removal and low-cost detection of phenolic pollutants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Polysaccharides with various molecular structures and morphology may influence the aggregation kinetics of nanoplastics. This study used various characterization methods to elucidate the heteroaggregation mechanism of polystyrene nanoplastics (PSNPs) in the presence of polysaccharides (ionic strength (IS) 1-800 mM NaCl and 0.01-60 mM CaCl 2 ). The results showed that under high IS, cellulose (CL) accelerated the heteroaggregation of PSNPs, and the aggregation rate of PSNPs increased by approximately 62.05 %, while amylose (AM) had little effect (10.38 %). Compared with AM (43.2 nm), the morphology of the CL (78.4 nm) gully had improved surface roughness, leading to its decisive role in the heteroaggregation of PSNPs. Quantum chemistry calculations indicated that van der Waals forces of PSNPs-CL systems (-217.28 kJ mol -1 ) were stronger than those of PSNPs-AM systems (-184.62 kJ mol -1 ) based on the subtle molecular conformation differences between CL and AM (opposite and same sides of OH groups in CL and AM, respectively). The morphology and molecular conformation of polysaccharides collaboratively controlled the heteroaggregation of PSNPs. Because the morphology of polysaccharides was based on their molecular conformation, the latter is the most critical factor. These findings provide new insights into the effects of PSNPs stability in the environment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Magnaporthe oryzae is a devastating fungal pathogen that causes the rice blast disease worldwide. The post-translational modification of ADP-ribosylation holds significant importance in various fundamental biological processes. However, the specific function of this modification in M. oryzae remains unknown. This study revealed that Poly(ADP-ribosyl)ation (PARylation) executes a critical function in M. oryzae. M. oryzae Poly(ADP-ribose) polymerase 1 (PARP1) exhibits robust PARylation activity. Disruption of PARylation by PARP1 knock-out or chemical inhibition reveals its involvement in M. oryzae virulence, particularly in appressorium formation. Furthermore, we identified two M. oryzae 14-3-3 proteins, GRF1 and GRF2, as substrates of PARP1. Deletion of GRF1 or GRF2 results in delayed and dysfunctional appressorium, diminished plant penetration, and reduced virulence of the fungus. Biochemical and genetic evidence suggest that PARylation of 14-3-3s is essential for its function in M. oryzae virulence. Moreover, PARylation regulates 14-3-3 dimerization and is required for the activation of the mitogen-activated protein kinases (MAPKs), Pmk1 and Mps1. GRF1 interacts with both Mst7 and Pmk1, and bridges their interaction in a PARylation-dependent manner. This study unveils a distinctive mechanism that PARylation of 14-3-3 proteins controls appressorium formation through MAPK activation, and could facilitate the development of new strategies of rice blast disease control., (© 2024. The Author(s).)

Breast cancer, the most common cancer among women worldwide, lacks specific tumor markers for accurate diagnosis. Recent advances have highlighted tumor-derived exosomes as a promising non-invasive biomarker for cancer detection. Continuous monitoring of surface protein markers on exosomes in the blood could offer valuable insights for breast cancer diagnosis. However, integrating the isolation and detection of exosomes from whole blood is bulky, time-consuming, and requires professional operations. To address this difficulty, we developed a method of integrated centrifugal disk chip (CD chip) exosome enrichment directly from whole blood followed by a colorimetric visualization strategy for multiplex analysis. The disc consists of multi-chambers and multi-microchannels with immediate smartphone-enabled processing of colorimetric results. The combination of CEA + CA125 + EGFR on-chip detection could significantly differentiate the different stages of cancer in tumor-bearing mice and successfully distinguish between breast cancer patients and healthy individuals. Crucially, small volumes (100 μL) of blood samples were adequate. In addition, the chip was simple and fast, with results within 10 min, which provides immediate exosomal information through consecutive blood sampling, which could potentially result in a more timely and well-informed clinical breast cancer diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

We report on a photochemical reaction of silyl enol ethers with iminoiodinanes. This aza Rubottom reaction provides a direct access towards α-amino carbonyl compounds under catalyst free reaction conditions with light as the sole source of energy. Control experiments suggest the participation of triplet nitrene intermediates.

Background: Diabetic foot ulcers (DFUs) are a common and serious complication of diabetes, often leading to amputation and decreased quality of life. Current treatment methods have limited success rates, highlighting the need for new approaches. This study investigates the potential of tibial transverse transport (TTT) to promote wound healing in DFUs., Methods: To test this hypothesis, the study used New Zealand White rabbits to establish a diabetic model and simulate foot ulcers, followed by the treatment of unilateral TTT or bilateral TTT. The study employed histological analysis, flow cytometry, ELISA, and qPCR to assess the impact of TTT on tissue repair and endothelial progenitor cell (EPC) mobilization and homing, aiming to understand the underlying biological processes in wound healing., Results: TTT significantly enhanced wound healing in diabetic rabbit foot ulcers. Specifically, bilateral TTT led to complete wound healing by day 19, faster than the unilateral TTT group, which healed by day 26, and the sham operation group, which nearly healed by day 37. Histological analysis showed improved tissue architecture, collagen deposition, and neovascularization in TTT-treated groups. Furthermore, TTT treatment resulted in a significant increase in VEGFR2 expression and VEGFR2/Tie-2 positive cells, particularly in the bilateral group. These findings were corroborated by qPCR results, which showed increased expression of VEGFA and CXCL12 by TTT. Conclusions: TTT may be a promising treatment for DFUs, significantly enhancing wound healing by stimulating EPC mobilization and homing mediated angiogenesis. This novel approach could substantially improve treatment outcomes for diabetic patients with chronic foot ulcers.

The effectiveness of chemokinetic therapy nanozymes is severely constrained because of the low H 2 O 2 levels in the tumor microenvironment. Unlike other self-produced H 2 O 2 nanozymes, the N-CNTs-encapsulated CoNi alloy (CoNiCoNC) with glucose oxidase and lactate oxidase activities has two ways to produce H 2 O 2 . It can facilitate the transformation of glucose and lactic acid into H 2 O 2 simultaneously. First, the H 2 O 2 generation pathway is favorable for aggravating energy metabolism. Second, some produced H 2 O 2 can be decomposed by CoNiCoNC to H 2 O and O 2 with the 4e - pathway to alleviate the TME hypoxia. Third, H 2 O 2 can be catalyzed to form OH to enhance reactive oxygen species (ROS) content. Through proteomic analysis, nanozymes substantially impact the metabolic pathways of cancer cells because of their aggravating energy metabolism. The high levels of ROS can cause mitochondrial lipid peroxidation and cellular ferroptosis. Consequently, the two-way H 2 O 2 -selective nanoenzymatic platform realizes the synergistic effect of starvation therapy and chemokinetics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Despite the widespread detection of polybrominated diphenyl ethers in aquatic ecosystems, their long-term effects on sediment multifunctionality remain unclear. Herein, a 360-day microcosm experiment was conducted to investigate how decabromodiphenyl ether (BDE-209) contamination at different levels (0.2, 2, and 20 mg/kg dry weight) affects sediment multifunctionality, focusing on carbon (C), nitrogen (N), phosphorus (P), and sulfur (S) cycling. Results showed that BDE-209 significantly increased sediment total organic carbon, nitrate, ammonium, available phosphorus, and sulfide concentrations, but decreased sulfate. Additionally, BDE-209 significantly altered key enzyme activities related to nutrient cycling. Bacterial community dissimilarity was positively correlated with nutrient variability. Long-term BDE-209 exposure inhibited C degradation, P transport and regulation, and most N metabolic pathways, but enhanced C fixation, methanogenesis, organic P mineralization, inorganic P solubilization, and dissimilatory sulfate reduction pathways. These changes were mainly regulated by microbial ecological clusters and keystone taxa. Overall, sediment multifunctionality declined under BDE-209 stress, primarily related to microbial co-occurrence network complexity and ecological cluster diversity. Interestingly, sediment C and N cycling had greater impacts on multifunctionality than P and S cycling. This study provides crucial insights into the key factors altering multifunctionality in contaminated sediments, which will aid pollution control and mitigation in aquatic ecosystems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The triglyceride-glucose (TyG) index is recognized as a robust indicator for evaluating insulin resistance (IR). Despite the well-documented anti-aging biological functions of Klotho protein, its correlation with the TyG index remains unexplored., Methods: A cross-sectional analysis was conducted involving participants from the National Health and Nutrition Examination Surveys (NHANES) 2007-2016. The TyG index was computed using laboratory data, while serum Klotho concentrations was determined using ELISA kit. After adjusting potential confounding variables, multivariate regression models were employed to evaluate the association between the TyG index and Klotho protein levels among middle-aged and elderly females and males separately. Additionally, smooth curve fitting and segmented regression model were applied to investigate potential threshold effects and identify the inflection point., Results: A total of 6,573 adults qualified for inclusion, comprising 3,147 (47.88%) males and 3,426 (52.12%) females. Multivariate regression analysis revealed that females with a higher TyG index exhibited significantly lower serum Klotho concentrations (β=-83.41, 95% CI: -124.23 to -42.60, P < 0.0001). This association was not statistically significant in males (β = 15.40, 95% CI: -19.16 to 49.95, P = 0.3827). Subgroup analyses revealed a significant interaction effect by diabetes status in females (P-interaction = 0.0121), where non-diabetic females showed a stronger negative association between TyG index and serum Klotho levels compared to diabetic females. In the female group, when TyG index was divided into quartiles, individuals in the highest quartile of TyG index exhibited reduced levels of Klotho protein (Q4: -88.77 pg/ml) compared to those in the lowest quartile (Q1) after full adjustment (P = 0.0041). Segmented regression analysis indicated a turning point value of 9.4 in females. Notably, a 1-unit increase in TyG index was significantly associated with a decrease in Klotho levels by -111.43 pg/ml (95% CI: -157.34 to -65.52, P < 0.0001) when TyG index was below 9.4, while above this threshold, the association was not significant (Log likelihood ratio test: 0.009)., Conclusions: The findings highlight a non-linear correlation between the TyG index and serum Klotho concentrations among females, indicative of a saturation effect. This relationship was particularly pronounced in non-diabetic women. In contrast, no statistically significant association was observed in male participants., (© 2024. The Author(s).)

Ethnopharmacological Relevance: Sepsis-induced acute lung injury (ALI) presents with significant morbidity and mortality in clinical settings. Tanreqing Injection (TRQI) has been clinically recommended for the treatment of ALI; however, the specific active chemical constituents remain unidentified., Aim of the Study: This study aimed to elucidate the potential pharmacologically active components and the underlying mechanisms of TRQI in the treatment of sepsis-induced ALI., Materials and Methods: High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) techniques were employed to identify the effective chemical constituents of TRQI. Additionally, an in vitro study was conducted using Raw264.7 macrophage cells stimulated with lipopolysaccharide (LPS) to evaluate the inhibitory effects of TRQI. An acute lung injury model produced by LPS was intraperitoneal injection in mice to assess the ALI-inhibitory effect of TRQI. The lung's pathological characteristics were examined using hematoxylin and eosin staining. Enzyme-linked immunosorbent assay (ELISA) and QPCR were performed to confirm the pharmaceutical effect. Network pharmacology was employed for mechanistic exploration, incorporating GO, and PPI analyses of targets. Src inhibitor and JNK agonist used to investigate the dependence of associated signaling pathways., Results: Combining pharmacokinetic characteristics, lung first-pass effect and anti-inflammatory effects, the main components of TRQI for treating sepsis induced ALI were narrowed down to seven compounds: chlorogenic acid, scutellarin, wogonoside, oroxyloside, oroxylin A and baicalein. Network pharmacology indicated that Src/JNK signaling pathway, may be the main regulatory pathway for treatment of actue lung injury. Next by using Src inhibitor, Src inhibition partly diminished the protective effects of TRQI in LPS-injected mice. Pretreatment with JNK agonist anisomycin abolished the protective effects of lung injury in vivo., Conclusions: TRQI is injected, the seven compounds could be presented in vivo, which can improve ALI by inhibiting Src-JNK signaling., Competing Interests: Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☐The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024. Published by Elsevier B.V.)

Atomic-resolution scanning transmission electron microscopy (STEM) characterization requires precise tilting of the specimen to a high symmetric zone axis, which is usually processed in reciprocal space by following the diffraction patterns. However, for small-sized nanocrystalline materials, their diffraction patterns are often too faint to guide the tilting process. Here, a simple and effective tilting method is developed based on the diffraction contrast change of the shadow image in the Ronchigram. The misorientation angle of the specimen can be calculated and tilted to the zone axis based on the position of the shadow image with lowest intensity. This method requires no prior knowledge of the sample and the maximum misorientation angle that can be corrected is >±6.9° with sub-mrad accuracy. It operates in real space, without recording the diffraction patterns of the specimens, making it particularly effective for nanocrystalline materials. Combined with the scripting to control the microscope, the sample can be automatically tilted to the zone axis under low dose conditions (<0.17 e -  Å - 2  s -1 ), facilitating the imaging of beam sensitive materials such as zeolites or metal-organic frameworks. This automated tilting method can significantly contribute to the atomic-scale characterization of the nanocrystalline materials by STEM imaging., (© 2024 Wiley‐VCH GmbH.)

Chlorpyrifos (CPF) is one of the organophosphorus pesticides widely used throughout the world. Epidemiological studies suggested a link between CPF exposure and neurologic disorders, while the molecular mechanisms remain inconclusive. In the present study, we investigated the impacts of chlorpyrifos-oxon (CPO), the major toxic CPF metabolite, on cell apoptosis, and explored possible mechanism associated with endoplasmic reticulum (ER) stress in SH-SY5Y cells. Results showed that CPO exposure induced dose-dependent apoptosis and expression of ER stress-related proteins in SH-SY5Y cells. Pretreatment with 4-PBA (an ER stress inhibitor) effectively inhibited the expression of GRP78, GRP94, p-IRE1α, and XBP1-s, and apoptotic events. Pretreatment with STF-083010 (an IRE1α inhibitor) partially attenuated CPO-induced apoptosis. In addition, CPO exposure significantly evoked the generation of reactive oxygen species (ROS) which could be eliminated by pretreatment of 4-PBA. Of note, buffering the ROS generation with antioxidant NAC had little impact on the expression of p-IRE1α, and only partially attenuated CPO-induced apoptosis. In contrast, co-pretreatment with NAC and STF-083010 effectively inhibited CPO-induced apoptotic events. Collectively, our results indicate that CPO exposure exerts neuronal cytotoxicity via ER stress downstream-regulated IRE1α/XBP1 signaling pathway and ROS generation-triggered apoptosis. These findings highlight the role of ER stress in CPF-induced neurotoxicity, and provide a promising target for the intervention of organophosphate-associated neurodegenerative diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which spreads rapidly all over the world. The main protease (M pro ) is significant to the replication and transcription of viruses, making it an attractive drug target against coronaviruses. Here, we introduce a series of novel inhibitors which are designed de novo through structure-based drug design approach that have great potential to inhibit SARS-CoV-2 M pro in vitro. High-resolution structures show that these inhibitors form covalent bonds with the catalytic cysteine through the novel dibromomethyl ketone (DBMK) as a reactive warhead. At the same time, the designed phenyl group beside the DBMK warhead inserts into the cleft between H41 and C145 through π-π stacking interaction, splitting the catalytic dyad and disrupting proton transfer. This unique binding model provides novel clues for the cysteine protease inhibitor development of SARS-CoV-2 as well as other pathogens., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The ruby lattice is one of the tight-binding models which hosts a flat band in its electronic structure and has potential applications in future spintronics and quantum devices. However, the experimental realization of a ruby lattice in realistic materials remains elusive. Here, we have experimentally realized an atomic ruby lattice by fabricating monolayer CuCl 1+ x on a Au(111) substrate. Scanning tunneling microscopy/spectra (STM/STS) measurements combined with density-functional theory (DFT) calculations reveal that the Cu atoms are arranged in a ruby lattice in this monolayer. Moreover, a significant density of states (DOS) peak corresponding to the characteristic of a ruby system is observed, consistent with both the tight-binding model and first-principles calculations on the band structure. Our work provides a promising platform to explore the physics of the ruby model.

Background: On April 18, 2024, the U.S. Food and Drug Administration officially required updating of the "boxed warning" for T cell malignancies for all chimeric antigen receptor T cell (CAR-T) therapies. Given the clinical significance of these therapies, a rigorous safety assessment is paramount. However, comprehensive real-world safety studies have been lacking for the newly marketed CAR-T products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), which target B cell maturation antigen, especially regarding the risk of secondary malignancies. Therefore, we aimed to thoroughly analyze the adverse events (AEs) information in the FDA Adverse Event Reporting System (FAERS) database to comprehensively understand the safety risks of ide-cel and cilta-cel., Methods: We extracted AE reports related to ide-cel and cilta-cel from the FAERS database (https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html.) from January 1, 2019 to December 31, 2023. Disproportionality analysis and Bayesian analysis were used to identify risk signals across subgroups and specific cases (including for death and secondary malignancies). Weibull distribution analysis was employed to determine the time to AE onset., Results: A total of 695 AE reports for ide-cel and 848 for cilta-cel were included in the FAERS database. This analysis identified 81 positive signals for ide-cel and 74 for cilta-cel. Notably, comparisons with the drug labels revealed "unexpected signals," including febrile bone marrow aplasia (reporting odds ratio=69.10; confidence interval 39.12-122.03) and plasma cell myeloma (12.45; 8.18-18.95) for ide-cel, and increased serum ferritin (24.98; 8.0-77.58) and large intestine perforation (18.57; 5.98-57.69) for cilta-cel. Both drugs showed a higher AE incidence among male recipients and patients aged ≥65 years, although female recipients faced a greater risk. Most AEs occurred at the early stage of administration. However, secondary malignancies were detected for both drugs, primarily occurring one-year post-administration., Conclusion: This study provides a foundation for understanding the safety profile of CAR-T cell therapy, particularly in relation to the emergence of secondary malignancies. Such insights are helpful for clinical decision-making and the safe and effective utilization of these therapeutic agents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Lin, Zhu, Yin, Liu, Lei and Feng.)

lncRNA can regulate tumorigenesis development and distant metastasis of colorectal cancer (CRC). However, the detailed molecular mechanisms are still largely unknown. Using RNA-sequencing data, RT-qPCR, and FISH assay, we found that HIF1A-AS2 was upregulated in CRC tissues and associated with poor prognosis. Functional experiments were performed to determine the roles of HIF1A-AS2 in tumor progression and we found that HIF1A-AS2 can promote the proliferation, metastasis, and aerobic glycolysis of CRC cells. Mechanistically, HIF1A-AS2 can promote FOXC1 expression by sponging miR-141-3p. SP1 can transcriptionally activate HIF1A-AS2. Further, HIF1A-AS2 can be packaged into exosomes and promote the malignant phenotype of recipient tumor cells. Taken together, we discovered that SP1-induced HIF1A-AS2 can promote the metabolic reprogramming and progression of CRC via miR-141-3p/FOXC1 axis. HIF1A-AS2 is a promising diagnostic marker and treatment target in CRC., (© 2024. The Author(s).)

The intestine constantly encounters and adapts to the external environment shaped by diverse dietary nutrients. However, whether and how gut adaptability to dietary challenges is compromised in ulcerative colitis is incompletely understood. Here, we show that a transient high-fat diet exacerbates colitis owing to inflammation-compromised bile acid tolerance. Mechanistically, excessive tumor necrosis factor (TNF) produced at the onset of colitis interferes with bile-acid detoxification through the receptor-interacting serine/threonine-protein kinase 1/extracellular signal-regulated kinase pathway in intestinal epithelial cells, leading to bile acid overload in the endoplasmic reticulum and consequent apoptosis. In line with the synergy of bile acids and TNF in promoting gut epithelial damage, high intestinal bile acids correlate with poor infliximab response, and bile acid clearance improves infliximab efficacy in experimental colitis. This study identifies bile acids as an "opportunistic pathogenic factor" in the gut that would represent a promising target and stratification criterion for ulcerative colitis prevention/therapy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Mitochondrial DNA (mtDNA) is a unique genetic material characterized by maternal inheritance. It possesses a circular structure devoid of histone protection and exhibits low cellular abundance, which poses great challenges for its sensitive and selective detection at the living cell level. Herein, we have designed three bis-naphthylimide probes with varying linker lengths (NANn-OH, n = 0, 2, 6), facilitating the formation of distinct twisted or folded molecular conformations in the free state. These probes emit the red fluorescence around 627 nm with different fluorescence quantum yields (Φ NAN0-OH = 0.0016, Φ NAN2-OH = 0.0136, and Φ NAN6-OH = 0.0125). When encountering mtDNA (0.4-3.4 μg/mL), these probes undergo conformational changes depending on the length of the attached C-strand and exhibit a gradually increasing fluorescence signal around 453 nm. The fluorescence intensity increased to 13.5-fold, 1.9-fold, and 8.2-fold, respectively. Notably, the red fluorescence intensities around 627 nm remain constant throughout this process, thus serving as an inherent correction mechanism for proportional fluorescence signal enhancement to improve selectivity and sensitivity. NAN0-OH, NAN2-OH, and NAN6-OH showed good linearity for mtDNA in the range of 0.4-3.4 μg/mL with detection limits of LOD NAN0-OH = 1.04 μg/mL, LOD NAN2-OH = 1.10 μg/mL, and LOD NAN6-OH = 1.15 μg/mL. Cellular experiments reveal that NAN6-OH effectively monitors curcumin-induced mtDNA damage in HepG-2 cells while enabling monitoring of genetic mtDNA damage. We anticipate that this tool holds significant potential for the precise evaluation of maternal genetic defects, thereby enhancing hypersensitive assessment in clinical medicine.

Transfer printing is a technology widely used in the production of flexible electronics and vertically stacked devices, which involves the transfer of predefined electronic components from a rigid donor substrate to a receiver substrate with a stamp, potentially avoiding the limitations associated with lithographic processes. However, the stamps typically used in transfer printing have several limitations related to unwanted organic solvents, substantial loading, film damage, and inadequate adhesion switching ratios. This study introduces a thermally responsive phase-change stamp for efficient and damage-free transfer printing inspired by the adhesion properties observed during water freezing and ice melting. The stamp employs phase-change composites and simple fabrication protocols, providing robust initial adhesion strength and switchability. The underlying mechanism of switchable adhesion is investigated through experimental and numerical studies. Notably, the stamp eliminates the need for extra preload by spontaneously interlocking with the ink through in situ melting and crystallization. This minimizes ink damage and wrinkle formation during pickup while maintaining strong initial adhesion. During printing, the stamp exhibits a sufficiently weak adhesion state for reliable and consistent release, enabling multiscale, conformal, and damage-free transfer printing, ranging from nano- to wafer-scale. The fabrication of nanoscale short-channel transistors, epidermal electrodes, and human-machine interfaces highlights the potential of this technique in various emerging applications of nanoelectronics, nano optoelectronics, and soft bioelectronics.

We have developed a cryogen-free, low-temperature terahertz scanning tunneling microscope (THz-STM). This system utilizes a continuous-flow cryogen-free cooler to achieve low temperatures of ∼25 K. Meanwhile, an ultra-small ultra-high vacuum chamber results in the reduction of the distance from sample to viewport to only 4 cm. NA = 0.6 can be achieved while placing the entire optical component, including a large parabolic mirror, outside the vacuum chamber. Thus, the convenience of optical coupling is much improved without compromising the performance of STM. Based on this, we introduced THz pulses into the tunnel junction and constructed the THz-STM, achieving atomic-level spatial resolution in THz-driven current imaging and sub-picosecond (sub-ps) time resolution in autocorrelation signals during pump-probe measurements. Experimental data from various representative samples are presented to showcase the performance of the instrument, establishing it as an ideal platform for studying non-equilibrium dynamic processes at nanoscale., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

This paper proposed an X-band phase shifter for the very compact inverse Compton scattering gamma-ray source program at Tsinghua University and conducted its structure design, numerical simulation, fabrication, cold test, and high-power testing. This phase shifter is composed of a polarizer, circular waveguide, and a piston with a choke structure. The simulation results show that the reflection coefficient of the phase shifter is under -40 dB and the insertion coefficient exceeds -0.06 dB at the operating frequency of 11.424 GHz. The phase variation is 20°/mm, and a linear phase change from 0° to 360° can be achieved with a piston displacement of 18 mm. The manufactured phase shifter has exhibited good performance in the cold test by using the vector network analyzer. After 16 h conditioning in the Tsinghua X-band high-power test stand, the phase shifter reached a peak power of 72 MW at 230 ns pulse width and a peak power of 82 MW at 130 ns pulse width. After processing signals from the high-speed oscilloscope, it was found that the transmission phase variations were in good agreement with the simulation results., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

An in-depth multiomic molecular characterization of PARP inhibitors revealed a distinct poly-pharmacology of niraparib (Zejula) mediated by its interaction with lanosterol synthase (LSS), which is not observed with other PARP inhibitors. Niraparib, in a similar way to the LSS inhibitor Ro-48-8071, induced activation of the 24,25-epoxysterol shunt pathway, which is a regulatory signaling branch of the cholesterol biosynthesis pathway. Interestingly, the combination of an LSS inhibitor with a PARP inhibitor that does not bind to LSS, such as olaparib, had an additive effect on killing cancer cells to levels comparable with niraparib as a single agent. In addition, the combination of PARP inhibitors and statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, an enzyme catalyzing the rate-limiting step in the mevalonate pathway, had a synergistic effect on tumor cell killing in cell lines and patient-derived ovarian tumor organoids. These observations suggest that concomitant inhibition of the cholesterol biosynthesis pathway and PARP activity might result in stronger efficacy of these inhibitors against tumor types highly dependent on cholesterol metabolism., Significance: The presented data indicate, to our knowledge, for the first time, the potential benefit of concomitant modulation of cholesterol biosynthesis pathway and PARP inhibition and highlight the need for further investigation to assess its translational relevance., (©2024 The Authors; Published by the American Association for Cancer Research.)

The cerebellum, a phylogenetically ancient brain region, has long been considered strictly a motor control structure. Recent studies have implicated the cerebellum in cognition, sensation, emotion and autonomic function, making it an important target for further investigation. Here, we show that cerebellar Purkinje neurons in mice are activated by the hormone asprosin, leading to enhanced thirst, and that optogenetic or chemogenetic activation of Purkinje neurons induces rapid manifestation of water drinking. Purkinje neuron-specific asprosin receptor (Ptprd) deletion results in reduced water intake without affecting food intake and abolishes asprosin's dipsogenic effect. Purkinje neuron-mediated motor learning and coordination were unaffected by these manipulations, indicating independent control of two divergent functions by Purkinje neurons. Our results show that the cerebellum is a thirst-modulating brain area and that asprosin-Ptprd signaling may be a potential therapeutic target for the management of thirst disorders., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)