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Mustard gas causes irreversible damage upon inhalation or contact with the human body. Consequently, the development of adsorbents for effective interception of mustard gas at low concentrations and high flow rates is an urgent necessity. Here we report a stable porous pillar[5]arene-containing metal–organic framework (MOF) based on zirconium (EtP5-Zr-scu), demonstrating that embedding pillar[5]arene units in MOFs can provide specific binding sites for efficient adsorption of a mustard gas simulant, 2-chloroethyl ethyl sulfide (CEES). EtP5-Zr-scuachieves a higher capacity and more rapid adsorption compared to its counterpart without embedded pillar[5]arene units (H4tcpt-Zr-scu) and perethylated pillar[5]arene (EtP5) alone. Single crystal X-ray diffraction and solid-state nuclear magnetic resonance reveal that the enhanced performance of EtP5-Zr-scuis derived from the host–guest complexation between CEES and pillar[5]arene moieties. Moreover, breakthrough experiments confirmed that the interception performance of EtP5-Zr-scuagainst CEES (800 ppm, 120 mL/min) was significantly improved (566 min/g) compared with H4tcpt-Zr-scu(353 min/g) and EtP5(0.873 min/g), attributed to the integration of open channels with specific recognition sites. This work marks a significant advancement in the development of macrocycle-incorporated crystalline framework materials with recognition sites for the efficient capture of guest molecules.

Ultrasmall Au25(MPA)18clusters show great potential in biocatalysts and bioimaging due to their well-defined, tunable structure and properties. Hence, in vivopharmacokinetics and toxicity of Au nanoclusters (Au NCs) are very important for clinical translation, especially at high dosages. Herein, the in vivohematological, tissue, and neurological effects following exposure to Au NCs (300 and 500 mg kg–1) were investigated, in which the concentration is 10 times higher than in therapeutic use. The biochemical and hematological parameters of the injected Au NCs were within normal limits, even at the ultrahigh level of 500 mg kg–1. Meanwhile, no histopathological changes were observed in the Au NC group, and immunofluorescence staining showed no obvious lesions in the major organs. Furthermore, real-time near-infrared-II (NIR-II) imaging showed that most of the Au25(MPA)18and Au24Zn1(MPA)18can be metabolized via the kidney. The results demonstrated that Au NCs exhibit good biosafety by evaluating the manifestation of toxic effects on major organs at ultrahigh doses, providing reliable data for their application in biomedicine.

The intricate tumor microenvironment (TME) always brings about unsatisfactory therapeutic effects for treatments, although nanomedicines have been demonstrated to be highly beneficial for synergistic therapies to avoid the side effects caused by the complexity and heterogeneity of cancer. Developing nanotheranostics with the functionalities of both synergistic therapies and TME regulation is a good strategy but is still in its infancy. Herein, an “all-in-one” nanoplatform for integrated diagnosis and treatment, namely, Carrier@ICG@DOX@FA (CIDF), is constructed. Benefiting from the bimetallic coordination of Eu3+-HTHA (4,4,4-trifluoro-1-(9-hexylcarbazol-3-yl)-1,3-butanedione) and Fe3+with the ligands in UiO-67, CIDF can simultaneously achieve two-photon fluorescence imaging, fluorescent lifetime imaging in deep tumors, and regulation of TME. Owing to its porosity, CIDF can encapsulate indocyanine green as photosensitizers and doxorubicin as chemotherapeutic agent, further realizing light-controlled drug release. Moreover, CIDF exhibited good biocompatibility and tumor targeting by coating with folic-acid-modified polymers. Both in vitro and in vivo experiments demonstrate the excellent therapeutic efficacy of CIDF through dual-modal-imaging-guided synergistic photothermal-, photodynamic-, and chemotherapy. CIDF provides a new paradigm for the construction of TME-regulated synergistic nanotheranostics and realizes the complete elimination of tumors without recurrence.

Major depressive disorder (MDD) is characterized by diverse debilitating symptoms that include loss of motivation and anhedonia. If multiple medications, psychotherapy, and electroconvulsive therapy fail in some patients with MDD, their condition is then termed treatment-resistant depression (TRD). MDD can be associated with abnormalities in the reward-system–dopaminergic mesolimbic pathway, in which the nucleus accumbens (NAc) and ventral tegmental area (VTA) play major roles. Deep brain stimulation (DBS) applied to the NAc alleviates the depressive symptoms of MDD. However, the mechanism underlying the effects of this DBS has remained elusive. In this study, using the chronic unpredictable mild stress (CUMS) mouse model, we investigated the behavioral and neurobiological effects of NAc-DBS on the multidimensional depression-like phenotypes induced by CUMS by integrating behavioral, in vivo microdialysis coupled with high-performance liquid chromatography–electrochemical detector (HPLC-ECD), calcium imaging, pharmacological, and genetic manipulation methods in freely moving mice. We found that long-term and repeated, but not single, NAc-DBS induced robust antidepressant responses in CUMS mice. Moreover, even a single trial NAc-DBS led to the elevation of the γ-aminobutyric acid (GABA) neurotransmitter, accompanied by the increase in dopamine (DA) neuron activity in the VTA. Both the inhibition of the GABAAreceptor activity and knockdown of the GABAA-α1gene in VTA-GABA neurons blocked the antidepressant effect of NAc-DBS in CUMS mice. Our results showed that NAc-DBS could disinhibit VTA-DA neurons by regulating the level of GABA and the activity of VTA-GABA in the VTA and could finally correct the depression-like behaviors in the CUMS mouse model.

Au nanoparticle sizes, as well as surface properties and Ti species of titanosilicate zeolite, have been identified to significantly influence the performances of Au–Ti bifunctional catalysts over propylene epoxidation with H2and O2to propylene oxide (HOPO process). Herein, we perform a convenient and efficient strategy to simultaneously regulate the properties of Au and Ti active sites by impregnating phosphate onto the uncalcined TS-1 zeolite (i.e., TS-1-B). The optimal P-modified TS-1-B-immobilized Au catalyst shows notably increased activity by 75% compared to the pristine Au/TS-1-B catalyst with a near PO selectivity and H2efficiency. We found that the introduction of phosphate conduces to the Au capture and formation of the smaller-sized Au nanoparticles with the smaller size over the TS-1-B zeolite, which promotes the generation of hydroperoxide species thereon and thus boosts the PO activity. Moreover, the moderate P modification could form highly active Ti species, reduce the surface defect, and enhance the Lewis acid sites over the TS-1-B zeolite, which makes for maintaining acceptable PO selectivity and H2efficiency under a high PO formation rate. We suggested this work could help develop efficient modification methods over Au–Ti bifunctional catalysts for this reaction.

In this work, TC4 members with different size surface waveform structures were prepared for vacuum brazing studies by laser powder bed fusion (LPBF) technique to obtain reliable joints, and the effects of the waveform structure, as well as process parameters on the structure and mechanical properties of the joints, were investigated. The experimental results show that there are two regions in the brazing joint: the isothermal solidification zone and the athermal solidification zone. Under the same brazing process, the microstructure in the brazing joint is more uniform, and the shear strength is higher with the increase of the waveform structure. When the brazing temperature was 980°C and the brazing time was 20min, the shear strength of the 0.5mm wave size joint reached 375MPa, which was 150% higher compared to the flat joint. The analysis by finite element analysis software found that the waveform structure joint can effectively reduce the residual stress in the joint, and alternating tensile and compressive stress fields will be formed in the joint, and the more obvious this stress field is with the increase of waveform size. The fracture paths of brazed joints with different waveform structures are different and are brittle fractures.

To investigate the prognostic factors in and role of postoperative radiotherapy (PORT) for surgically resected thymomas.

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The spoilage and forgery of perishable products such as food, drugs, and vaccines cause serious health hazards and economic loss every year. Developing highly efficient and convenient time–temperature indicators (TTIs) to realize quality monitoring and anticounterfeiting simultaneously is urgent but remains a challenge. To this end, a kind of colorimetric fluorescent TTI, based on CsPbBr3@SiO2nanoparticles with tunable quenching kinetics, is developed. The kinetics rate of the CsPbBr3-based TTIs is easily regulated by adjusting temperature, concentration of the nanoparticles, and addition of salts, stemming from the cation exchange effect, common-ion effect, and structural damage by water. Typically, when combined with europium complexes, the developed TTIs show an irreversible dynamic change in fluorescent colors from green to red upon increasing temperature and time. Furthermore, a locking encryption system with multiple logics is also realized by combining TTIs with different kinetics. The correct information only appears at specific ranges of time and temperature under UV light and is irreversibly self-erased afterward. The simple and low-cost composition and the ingenious design of kinetics-tunable fluorescence in this work stimulate more insights and inspiration toward intelligent TTIs, especially for high-security anticounterfeiting and quality monitoring, which is really conducive to ensuring food and medicine safety.

In this study, the Ti-Zr-Cu-Ni amorphous brazing filler was used to achieve vacuum brazing between TC4 titanium alloy manufactured by selective laser melting (SLM) and Inconel 718 superalloy. The microstructure of the brazed joint was mainly TC4 base metal/Widmanstätten structure/β-Ti + Ti2Cu/(Ti, Zr)2(Cu, Ni)/(Ti, Zr)2(Cu, Ni) + α-Ti/Fe2Ti + Cr7Ni3+ TiNi3+ Ni(Fe, Cr) solid solution/Inconel 718 base material. The influence of different brazing temperatures and brazing times on the microstructure and mechanical properties of the joint was studied. The distribution of residual stresses in the joints was analyzed by nanoindentation and EBSD. The mechanical properties of the intermetallic compounds in the joints and their effects on the mechanical properties of the joints were also investigated. When the brazing temperature was 930 °C and the brazing time was 20 min, the brazed joints with optimal mechanical properties were obtained, and the average shear strength of the joints reached 111.2 MPa. Fracture analysis showed that the cracks sprouted in the (Ti, Zr)2(Cu, Ni) and (Ti, Zr)2(Cu, Ni) + α-Ti two-phase zone and extended in this region. The fractured form was a brittle fracture, and the mechanical properties of the joint were dominated by Ti-based intermetallic compounds.

An adequate nutrient supply is essential for maintaining the function of highly active immune cells; however, in an environment of excessive inflammation, this nutrient supply aggravates inflammation. We propose a “hyperinflammatory starvation therapy” for various diseases caused by excessive metabolism by highly selective restriction of the supply of local nutrients. Here we developed a natural, physiologically triggered, injectable, nano-platelet vesicle-based extracellular matrix hydrogel (NPV-ECM). As a proof of concept, in representative excessive inflammatory disease diabetic wounds, we demonstrated that the NPV-ECM can selectively regulate nutrient transportation based on intermolecular interactions, remodel the local immune microenvironment, limit the state of excess metabolism, promote angiogenesis, and achieve wound healing. Moving into the clinic, we conducted a clinical trial in patients with diabetic foot ulcers to verify the safety and therapeutic effect of the NPV-ECM. This study provides an understanding of the preparation and application of natural ECM biomaterials for hyperinflammatory starvation therapy.

Many diseases and health conditions are closely related to various microbes, which participate in complex interactions with diverse drugs; nonetheless, the detailed targets of such drugs remain to be elucidated. Many existing studies have reported causal associations among drugs, gut microbes, or diseases, calling for a workflow to reveal their intricate interactions. In this study, we developed a systematic workflow comprising three modules to construct a Quorum Sensing-based Drug-Microbe-Disease (QS-DMD) database (http://www.qsdmd.lbci.net/), which includes diverse interactions for more than 8,000 drugs, 163 microbes, and 42 common diseases. Potential interactions between microbes and more than 8,000 drugs have been systematically studied by targeting microbial QS receptors combined with a docking-based virtual screening technique and in vitroexperimental validations. Furthermore, we have constructed a QS-based drug-receptor interaction network, proposed a systematic framework including various drug-receptor-microbe-disease connections, and mapped a paradigmatic circular interaction network based on the QS-DMD, which can provide the underlying QS-based mechanisms for the reported causal associations. The QS-DMD will promote an understanding of personalized medicine and the development of potential therapies for diverse diseases. This work contributes to a paradigm for the construction of a molecule-receptor-microbe-disease interaction network for human health that may form one of the key knowledge maps of precision medicine in the future.

N-methyl-d-aspartate (NMDA) receptors are heterotetramers comprising two GluN1 and two alternate GluN2 (N2A-N2D) subunits. Here we report full-length cryo-EM structures of the human N1-N2D di-heterotetramer (di-receptor), rat N1-N2C di-receptor and N1-N2A-N2C tri-heterotetramer (tri-receptor) at a best resolution of 3.0 Å. The bilobate N-terminal domain (NTD) in N2D intrinsically adopts a closed conformation, leading to a compact NTD tetramer in the N1-N2D receptor. Additionally, crosslinking the ligand-binding domain (LBD) of two N1 protomers significantly elevated the channel open probability (Po) in N1-N2D di-receptors. Surprisingly, the N1-N2C di-receptor adopted both symmetric (minor) and asymmetric (major) conformations, the latter further locked by an allosteric potentiator, PYD-106, binding to a pocket between the NTD and LBD in only one N2C protomer. Finally, the N2A and N2C subunits in the N1-N2A-N2C tri-receptor display a conformation close to one protomer in the N1-N2A and N1-N2C di-receptors, respectively. These findings provide a comprehensive structural understanding of diverse function in major NMDA receptor subtypes.

Background: The advent of robot-assisted thoracoscopic surgery (RATS) has completely revolutionized the modality of thymectomy, which could reportedly achieve equivalent efficacy compared with a minimally invasive approach. This study was conducted to further compare the perioperative outcomes between these two modalities. Methods: A retrospective single-center study that included patients receiving either a robotic or video-assisted thoracoscopic (VAT) thymectomy between February 2021 and January 2023 was conducted. All the patients were pathologically confirmed with thymic epithelial tumors. Clinical and pathological characteristics and perioperative outcomes were collected and compared between these two cohorts. Results: A total of 190 patients were included in this study, with 61 (32.1%) and 129 (67.9%) receiving robotic and video-assisted thymectomy, respectively. The clinicopathological characteristics were not significantly different between these 2 groups. The size of the resected specimens in the RATS cohort was larger than the VATS cohort [median (IQR), 13.0 (8.0–16.0) vs. 9.0 (6.7–12.0) cm, p< 0.001], while the procedural duration was longer for the RATS group than its counterpart [median (IQR), 105 (85–143) vs. 85 (69–115) min, p= 0.001]. Moreover, no other significant difference was observed between these two groups. Since more than half of the robotic thymectomy was performed using a subxiphoid approach, a subgroup analysis was further conducted. Similarly, the robotic group through a subxiphoid approach harbored a longer procedural duration, and the size of the specimens obtained was larger than the VATS group [median (IQR), 14.0 (11.0–16.5) vs. 12.5 (8.5–15.0) cm, p= 0.061]. Conclusions: The early clinical efficacy of robotic thymectomy was proven comparable to the established VATS approach, and such a modality might have strength when obtaining larger specimens, which could contribute to improving long-term efficacy. Despite the longer procedural duration recorded in the early stage of conducting robotic thymectomy, further accumulation would help decrease the time.

The small brown planthopper (Laodelphax striatellus(Fallén), Hemiptera: Delphacidae), is an important agricultural pest of rice, and neonicotinoid insecticides are commonly used for controlling L. striatellus. However, the sublethal effects of thiamethoxam on L. striatellusremain relatively unknown. In this study, an age-stage life table procedure was used to evaluate the sublethal effects of thiamethoxam on the biological parameters of L. striatellus. Additionally, activities of carboxylesterase, glutathione S-transferase, and cytochrome P450 monooxygenase in the third instar nymphs were analyzed. The results indicated that the survival time of F0adults and the fecundity of female adults decreased significantly after the third instar nymphs were treated with sublethal concentrations of thiamethoxam (LC150.428 mg/liter and LC300.820 mg/liter). The developmental duration, adult preoviposition period, total preoviposition period, and mean generation time of the F1generation increased significantly, whereas the fecundity of the female adults, intrinsic rate of increase (ri), and finite rate of increase (λ) decreased significantly. The oviposition period was significantly shorter for the insects treated with LC30than for the control insects. Neither sublethal concentrations had significant effects on the adult longevity, net reproduction rate (R0), or gross reproduction rate (GRR) of the F1generation. The activities of carboxylesterase, glutathione-S-transferase, and cytochrome P450 monooxygenase increased significantly after the thiamethoxam treatments. These results indicate that sublethal concentrations of thiamethoxam can inhibit L. striatelluspopulation growth and enhance detoxification enzyme activities.

Sentiment analysis on social networks mines users' opinions, emotions, and attitudes to derive useful insights into community opinions and can improve the sales strategies of e-commerce platforms. Existing sentiment analysis methods are primarily based on complex user social relations and text data. However, they only use social relations among users and ignore the interactions of user sentiment orientation. In this paper, we designed a novel USON model to learn user sentiment orientation in social networks that fuses the interaction of users and their opinions. We define the score of the user sentiment orientation according to the sentiment polarity distribution of the opinion datasets. Then, we rebuilt a user social network, which is an attribute network with scores of user sentiment orientation as node attributes and social relations as edges. Finally, we integrated user representations with opinion representations for sentiment analysis. Experimental results on Amazon and Yelp show that the performance of our proposed model is significantly higher than that of state-of-the-art methods. [ABSTRACT FROM AUTHOR]

ABSTRACTSocial epigenomics is an emerging field in which social scientist collaborate with computational biologists, especially epigeneticists, to address the underlying pathway for biological embedding of life experiences. This social epigenomics study included long-term childhood cancer survivors enrolled in the St. Jude Lifetime Cohort. DNA methylation (DNAm) data were generated using the Illumina EPIC BeadChip, and three social determinants of health (SDOH) factors were assessed: self-reported educational attainment, personal income, and an area deprivation index based on census track data. An epigenome-wide association study (EWAS) was performed to evaluate the relation between DNAm at each 5’-cytosine-phosphate-guanine-3’ (CpG) site and each SDOH factor based on multivariable linear regression models stratified by ancestry (European ancestry, n = 1,618; African ancestry, n = 258). EWAS among survivors of European ancestry identified 130 epigenome-wide significant SDOH–CpG associations (P< 9 × 10−8), 25 of which were validated in survivors of African ancestry (P< 0.05). Thirteen CpGs were associated with all three SDOH factors and resided at pleiotropic loci in cigarette smoking–related genes (e.g., CLDND1and CPOX). After accounting for smoking and body mass index, these associations remained significant with attenuated effect sizes. Seven of 13 CpGs were associated with gene expression level based on 57 subsamples with blood RNA sequencing data available. In conclusion, DNAm signatures, many resembling the effect of tobacco use, were associated with SDOH factors among survivors of childhood cancer, thereby suggesting that biologically distal SDOH factors influence health behaviours or related factors, the epigenome, and subsequently survivors’ health.

Structure–performance relationship is a complex issue in iron-catalyzed Fischer–Tropsch synthesis, and it is not easy to elucidate it by experimental investigations. First-principle calculation is a powerful method for explaining experimental results and guiding catalyst design. In this study, we investigated the reaction mechanisms of CH4formation and C–C coupling on four χ-Fe5C2surfaces and established the kinetic equations to compare the rates of CH4formation and C1+C1coupling reactions and determine the CH4/C2+selectivity. The results show that the geometry of the χ-Fe5C2surfaces has little effect on the formation rate of CH4; however, the C1+C1coupling reactions are significantly affected by the surface geometry. The C1+C1coupling reaction rates on the terraced-like (510) and (021) surfaces are much higher than those on the stepped-like (001) and (100) surfaces. Based on these results, we established a Brønsted–Evans–Polanyi (BEP) relationship between the effective barrier difference for CH4formation and C1+C1coupling (ΔEeff) and the adsorption energy of C+4H (ΔEC+4H) on χ-Fe5C2surfaces. ΔEC+4Hcan be used as a descriptor for CH4/C2+selectivity on different surfaces of χ-Fe5C2.

Objective To evaluate the efficacy and safety of fezolinetant for moderate to severe vasomotor symptoms (VMS) associated with menopause in East Asian women.Methods In this phase 3, randomized, double-blind study, postmenopausal women with moderate to severe VMS (minimum average frequency in the 10 days before randomization, ≥7/day or 50/week) received fezolinetant 30 mg/day or placebo (weeks 1–12), followed by an open-label extension phase with fezolinetant 30 mg/day (weeks 13–24). The co-primary endpoints were the mean changes in the daily frequency and severity of VMS at weeks 4 and 12.Results Among 301 participants, the difference in the least squares mean change (95% confidence interval) from baseline in the daily frequency of moderate to severe VMS versus placebo was −0.65 (−1.41 to 0.12) at week 4 and −0.55 (−1.35 to 0.26) at week 12. The differences in the least squares mean change from baseline in the VMS severity score versus placebo were −0.06 (−0.14 to 0.03) and −0.13 (−0.27 to 0.01) at weeks 4 and 12, respectively. Serious adverse events occurred in 0.7% of participants receiving fezolinetant in weeks 1 to 12, compared with 1.3% of those receiving placebo.Conclusions Fezolinetant was generally safe but did not reduce the frequency or severity of VMS versus placebo in postmenopausal women in this study. ClinicalTrials.Gov Identifier:NCT04234204

Objective: This study was performed to evaluate the clinical effect of skin redraping on lower eyelid epiblepharon accompanied by a medial epicanthal fold. Methods: This retrospective case series involved 572 eyes of 286 patients who underwent skin redraping surgery to treat lower eyelid epiblepharon accompanied by a medial epicanthal fold from January 2015 to May 2019. The postoperative surgical results were classified as “good”, “fair” and “poor”. The incision scars were assessed using the Vancouver scar scale. The patients’ subjective satisfaction and incidence of complications were also documented. Results: The mean patient age at the time of surgery was 6.9 ± 3.6 years (3–12 years), and the mean follow-up time was 32.6 ± 13.5 months (6–58 months). The clinical symptoms and severity of keratopathy were improved postoperatively. “Good” surgical outcomes were obtained in all patients, the mean Vancouver scar scale score was 1.1 ± 0.3, and hypertrophic scar formation did not occur. A total of 272 patients and their guardians were “very satisfied” with the cosmetic outcomes. Conclusion: Skin redraping was effective and endurable in the treatment of lower eyelid epiblepharon accompanied by a medial epicanthal fold. The postoperative scars were slight and nearly invisible, and no cases of recurrence were observed in this study.

Advanced and aggressive prostate cancer (PCa) depends on glutamine for survival and proliferation. We have previously shown that inhibition of glutaminase 1, which catalyzes the rate-limiting step of glutamine catabolism, achieves significant therapeutic effect; however, therapy resistance is inevitable. Here we report that while the glutamine carbon is critical to PCa survival, a parallel pathway of glutamine nitrogen catabolism that actively contributes to pyrimidine assembly is equally important for PCa cells. Importantly, we demonstrate a reciprocal feedback mechanism between glutamine carbon and nitrogen pathways which leads to therapy resistance when one of the two pathways is inhibited. Combination treatment to inhibit both pathways simultaneously yields better clinical outcome for advanced PCa patients.

Inconel 718 (IN718) superalloys with multi-size 3D waveform structures were prepared by selective laser melting (SLM) technology, and the transient liquid phase bonding (TLPB) of IN718 was carried out using a rapidly solidified BNi2 filler containing melting point depressant (MPD) elements. In this study, the microstructure and mechanical properties of TLPB joints after brazing at 1080 °C for 20 min were investigated, and the effects of different 3D waveform structures on the formation and properties of TLPB joints were analyzed. The experimental results show that there are three zones in the TLPB joint of IN718 superalloy: (i) the isothermally solidified zone (ISZ) consisting of γ-Ni solid solution, (ii) the athermally solidified zone (ASZ) consisting of Ni3B, CrB, Ni6Si2B phases, and fine Ni3Si particles, and (iii) the diffusion affected zone (DAZ) consisting of Cr rich borides and Cr-Nb-Mo rich borides. And a region with high Cr content was found in the ASZ. In addition, the shear strength of the joint increased gradually with the increase of the groove depth of the 3D waveform structure. The shear strength of the TLPB joints reached a maximum of 515.17 MPa when the groove depth of the IN718 3D waveform was 0.8 mm, and the fracture mode of the joints gradually changed from brittle fracture to mixed tough-brittle fracture.

Insufficient intracellular anabolism is a crucial factor involved in many pathological processes in the body1,2. The anabolism of intracellular substances requires the consumption of sufficient intracellular energy and the production of reducing equivalents. ATP acts as an ‘energy currency’ for biological processes in cells3,4, and the reduced form of NADPH is a key electron donor that provides reducing power for anabolism5. Under pathological conditions, it is difficult to correct impaired anabolism and to increase insufficient levels of ATP and NADPH to optimum concentrations1,4,6–8. Here we develop an independent and controllable nanosized plant-derived photosynthetic system based on nanothylakoid units (NTUs). To enable cross-species applications, we use a specific mature cell membrane (the chondrocyte membrane (CM)) for camouflage encapsulation. As proof of concept, we demonstrate that these CM-NTUs enter chondrocytes through membrane fusion, avoid lysosome degradation and achieve rapid penetration. Moreover, the CM-NTUs increase intracellular ATP and NADPH levels in situ following exposure to light and improve anabolism in degenerated chondrocytes. They can also systemically correct energy imbalance and restore cellular metabolism to improve cartilage homeostasis and protect against pathological progression of osteoarthritis. Our therapeutic strategy for degenerative diseases is based on a natural photosynthetic system that can controllably enhance cell anabolism by independently providing key energy and metabolic carriers. This study also provides an enhanced understanding of the preparation and application of bioorganisms and composite biomaterials for the treatment of disease.

Photon upconversion of lanthanides has been a powerful means to convert low-energy photons into high-energy ones. However, in contrast to the mostly investigated lanthanide ions, it has remained a challenge for the efficient upconversion of Nd3+due to the deleterious concentration quenching effect. Here we report an efficient strategy to enhance the upconversion of Nd3+through the Yb3+-mediated energy cycling in a core-shell-shell nanostructure. Both Nd3+and Yb3+are confined in the interlayer, and the presence of Yb3+in the Nd-sublattice provides a more matched energy for the upconversion transitions occurring at the intermediate state of Nd3+towards much better population at its emissive levels. Moreover, this design also minimizes the possible cross-relaxation processes at both intermediate level and the emissive levels of Nd3+which are the primary factors limiting the upconversion performance for the Nd3+-doped materials. Such energy cycling-enhanced upconversion shows promise in temperature sensing.

Supplemental digital content is available in the text.

Phototheranostics involving both fluorescence imaging and photodynamic therapy has been recognized to be potentially powerful for cancer treatment by virtue of various intrinsic advantages. However, the state-of-the-art materials in this area are still far from ideal toward practical applications, ascribed to their respective and collective drawbacks, such as inefficient imaging quality, inferior reactive oxygen species (ROS) production, the lack of subcellular-targeting capability, and dissatisfactory delivery. In this paper, these shortcomings are successfully addressed through the integration of finely engineered photosensitizers with aggregation-induced emission (AIE) features and well tailored nanocarrier systems. The yielded AIE NPs simultaneously exhibit broad absorption in the visible-light region, bright near-infrared fluorescence emission, high ROS generation, as well as tumor lysosomal acidity-activated and nucleus-targeted delivery functions, making them promising for precise and efficient phototheranostics. Both in vitroand in vivoevaluations show that the presented nanotheranostic systems bearing good photostability and appreciable biosecurity perform well in fluorescence imaging-guided photodynamic cancer therapy. This study thus not only extends the application scopes of AIE nanomaterials but also offers useful insights into constructing advanced cancer phototheranostics.

Objectives To investigate the relationship between coronary artery calcification and calcium deposition in cardiomyocytes.Methods Patients who underwent valve replacement plus surgical ablation for atrial fibrillation, together with left atrial appendage resection, were included. Coronary artery calcification (CAC) score was evaluated prior to surgery using dual-source computed tomography. Samples of left atrial appendage tissue were collected to analyse the following indicators: calcium deposition, alkaline phosphatase activity, calcium content, protein levels of runt-related transcription factor 2 (Runx2), osteopontin and β-catenin, and mRNA levels of osteopontin, endothelin and ghrelin. Relationships between CAC score and various indicators were analysed by univariate logistic or linear regression.Results Out of tissue from eight patients, CAC score was not correlated with cardiomyocyte calcification (odds ratio [OR] 0.984 and OR 0.983; von Kossa or alizarin red staining, respectively). CAC score showed an inverse linear correlation with Runx2 protein (β = –0.75), but was not correlated with osteopontin (β = –0.52) or β-catenin protein (β = –0.56), mRNA levels of osteopontin, endothelin and ghrelin (β = 0.13, 0.02, and 0.02, respectively), alkaline phosphatase activity (β = 0.56), or calcium content (β = –0.22).Conclusions Coronary artery calcification was not correlated with calcium deposition in cardiomyocytes.

We propose a microlens array-type snapshot hyperspectral microscope system that can provide spatial spectrum sampling according to detector frame rates for the biomedical domain. The system uses a shared optical path design. One path is used to perform direct microscopic imaging with high spatial resolution, while the other is used to collect microscopic images through a microlens array; the images are then spatially cut and reimaged such that they are spaced simultaneously by the prism-grating type hyperspectral imager’s dispersion. Rapid acquisition of a three-dimensional data cube measuring 28×14×180 (x×y×λ) can be performed at the detector’s frame rate. The system has a spatial resolution of 2.5 µm and can achieve 180-channel sampling of a 100 nm spectrum in the 400–800 nm spectral range with spectral resolution of approximately 0.56 nm. Spectral imaging results from biological samples show that the microlens array-type snapshot hyperspectral microscope system may potentially be applied in real-time biological spectral imaging.

Atherosclerosis (AS) is the principal cause of heart attack, sudden cardiac death, stroke, and necrosis of the extremities, in which significant changes in gene expression associated with inflammation are found. However, the molecular mechanisms of AS are not clearly elucidated. In this study, ApoE−/−mice were fed with a high fat diet for 12 weeks to induce atherosclerosis and half of the mice were treated with tanshinone IIA (TAN). Then sequencing analysis was performed to investigate the expression patterns of ncRNAs in AS plaques obtained from mice treated with TAN and AS Model mice. A total of 22 long noncoding RNAs (lncRNAs), 74 microRNAs (miRNAs), 13 circular RNAs (circRNAs), and 1359 mRNAs in AS plaque were more significantly regulated from TAN mice, compared with model mice. Bioinformatics tools and databases were employed to investigate the potential ncRNA functions and their interaction. Our data showed that the most significantly pathways regulated by TAN were associated with inflammation, and involved in the signaling pathways of Ras, Rap1, MAPK, cAMP, T cell receptor, and so on. In addition, the competitive endogenous RNA (ceRNA) network had been constructed and the core nodes included circ‐Tns3/let‐7d‐5p/Ctsl, circ‐Wdr91/miR‐378a‐5p/Msr1, and circ‐Cd84/ miR‐30c/ Tlr2. The DERNAs were validated by quantitative RT‐PCR and dual luminescence reporter assay in RAW264.7 cells in vitro. This study identified ceRNAs network regulated by TAN and elucidated the ncRNAs profile and signal pathways to attenuate AS comprehensively. This research would contribute to further research on the pathogenesis of AS, and facilitate the development of novel therapeutics targeting ncRNAs. Tanshinone IIA (TNA), a compound that has been used for cardiovascular diseases for decades, regulates the long non‐coding RNA network associated with inflammation.

Deep brain stimulation (DBS) applied to the nucleus accumbens (NAc) alleviates the depressive symptoms of major depressive disorders. We investigated the mechanism of this effect by assessing gene expression and RNA methylation changes in the ventral tegmental area (VTA) following NAc-DBS in a chronic unpredictable mild stress (CUMS) mouse model of depression. Gene expression and N6-methyladenosine (m6A) levels in the VTA were measured in mice subjected to CUMS and then DBS, and transcriptome-wide m6A changes were profiled using immunoprecipitated methylated RNAs with microarrays, prior to gene ontology analysis. The expression levels of genes linked to neurotransmitter receptors, transporters, transcription factors, neuronal activities, synaptic functions, and mitogen-activated protein kinase and dopamine signaling were upregulated in the VTA upon NAc-DBS. Furthermore, m6A modifications included both hypermethylation and hypomethylation, and changes were positively correlated with the upregulation of some genes. Moreover, the effects of CUMS on gene expression and m6A-mRNA modification were reversed by DBS for some genes. Interestingly, while the expression of certain genes was not changed by DBS, long-term stimulation did alter their m6A modifications. NAc-DBS-induced modifications are correlated largely with upregulation but sometimes downregulation of genes in CUMS mice. Our findings improve the current understanding of the molecular mechanisms underlying DBS effects on depression.

Herein, spin-polarized density functional theory calculations are performed to investigate CO adsorption and activation on both perfect and defective η-Fe2C surfaces. The equilibrium shape of the η-Fe2C crystallite is first predicted by Wulff construction based on the surface energies of the experimentally observed crystal facets. The thermodynamically stable η-Fe2C (011) surface is observed to have the largest percentage followed by the (110), (211), and (121) surfaces. The H-assisted CO dissociation via the HCO* intermediate is suggested as the preferred CO activation pathway on these four mostly exposed η-Fe2C surfaces, while the direct CO dissociation is the preferred CO activation pathway on the corresponding four defective η-Fe2C surfaces because the presence of the carbon vacancy leads to less electrons donated to the absorbed CO by the surface Fe atoms based on Bader charge analysis. The insights reported here could shed new light on the rational design and manipulation of η-Fe2C Fischer–Tropsch catalysts.

The discovery of the bone–gut axis linking bone metabolism to gut microbiota (GM) dysbiosis has revolutionized our understanding of managing degenerative skeletal diseases. Targeting GM regulation has emerged as a promising approach to osteoporosis treatment. Herein, we develop propolis nanoemulsions (PNEs) with enhanced gastrointestinal stability and oral bioavailability for GM-based osteoporosis therapy. Orally administered PNEs exhibit superior antiosteoporosis efficacy in an ovariectomized (OVX) mouse model by modulating the GM structure and metabolites and restoring the intestinal barrier function. Multiomics analysis reveals that a reduction in Streptococcusabundance and an increase in the GM metabolite l-arginine are key factors in osteoporosis management. These changes suppress osteoclast activity and enhance osteoblast function, leading to balanced bone remodeling and, thus, significant antiosteoporotic effects via the gut–bone axis. Our results deepen insights into the intricate relationship between GM and bone remodeling, suggesting a promising strategy that maintains the homeostasis of the GM structure and metabolite for osteoporosis treatment.

Sepsis, a life-threatening condition caused by a dysregulated immune response to infection, leads to systemic inflammation, immune dysfunction, and multiorgan damage. Various oxidoreductases play a very important role in balancing oxidative stress and modulating the immune response, but they are stored inconveniently, environmentally unstable, and expensive. Herein, we develop multifunctional artificial enzymes, CeO2and Au/CeO2nanozymes, exhibiting five distinct enzyme-like activities, namely, superoxide dismutase, catalase, glutathione peroxidase, peroxidase, and oxidase. These artificial enzymes have been used for the biocatalytic treatment of sepsis via inhibiting inflammation and modulating immune responses. These nanozymes significantly reduce reactive oxygen species and proinflammatory cytokines, achieving multiorgan protection. Notably, CeO2and Au/CeO2nanozymes with enzyme-mimicking activities can be particularly effective in restoring immunosuppression and maintaining homeostasis. The redox nanozyme offers a promising dual-protective strategy against sepsis-induced inflammation and organ dysfunction, paving the way for biocatalytic-based immunotherapies for sepsis and related inflammatory diseases.

Essentially clearing the structure–activity relationship between iron carbide catalysts involving multiple active centers to understand the reaction mechanism of CO hydrogenation conversion process is still a great challenge. Here, two main micro-environment factors, namely electronic properties and geometrical effects were found to have an integrated effect on the mechanism of CO hydrogenation conversion, involving active sites on multiple crystal phases. The Bader charge of the surface Fe atoms on the active sites had a guiding effect on the CO activation pathway, while the spatial configuration of the active sites greatly affected the energy barriers of CO activation. Although the defective surfaces were more conducive to CO activation, the defective sites were not the only sites to dissociate CO, as CO always tended to dissociate in a wider area. This synergistic effect of the micro-environment also occurred during the CO conversion process. Surface C atoms on relatively flat configurations were more likely to form methane, while the electronic properties of the active sites could effectively describe the C–C coupling process, as well as distinguish the coupling mechanisms.

Bacterial infectious diseases, especially those caused by Gram-positive bacteria, have been seriously threatening human health. Preparation of a multifunctional system bearing both rapid bacterial differentiation and effective antibacterial effects is highly in demand, but remains a severe challenge. Herein, we rationally designed and successfully developed a sequence of aggregation-induced emission luminogens (AIEgens) with orderly enhanced D–A strength. Evaluation of structure–function relationships reveals that AIEgens having intrinsic positive charge and proper ClogP value are able to stain Gram-positive bacteria. Meanwhile, one of the presented AIEgens (TTPy) can generate reactive oxygen species (ROS) in extraordinarily high efficiency under white light irradiation due to the smaller singlet–triplet energy gap. Thanks to the NIR emission, excellent specificity to Gram-positive bacteria, and effective ROS generation efficiency, TTPy has been proved to perform well in selective photodynamic killing of Gram-positive bacteria in vitro, such as S. aureusand S. epidermidis, even in S. aureus-infected rat wounds.

By using the shake-flask method, the acetoguanamine solubilities in water, acetonitrile, methanol, n-butanol, isopropanol, isobutanol, ethanol, n-propanol, N,N-dimethylformamide (DMF), 1,4-dioxane, ethyl acetate, and ethylene glycol (EG) were acquired over the temperatures from 283.15 to 323.15 K at ambient pressure (p= 101.2 kPa). The mole fraction of acetoguanamine in equilibrated liquor increased as the temperature increased and followed the order in different solvents: DMF > EG > ethyl acetate > 1,4-dioxane > n-butanol > isobutanol > n-propanol > isopropanol > ethanol > methanol > water > acetonitrile. The acquired solubility was correlated via the Apelblat equation. The largest root-mean-square deviation value and largest relative average deviation were, respectively, 28.12 × 10–6and 2.38 × 10–2.

From motor proteins to molecular machines, supramolecular chemistry has been revealed as a remarkable link to bridge the gap between biology, chemistry, and materials. Taking inspiration from the dynamic, reversible, and directional manner of non-covalent interactions that can respond to diversiform external stimuli, supramolecular nanovalves installed on the surface of inorganic or hybrid nanocarriers have received extensive attention in stimuli-responsive delivery of small drug molecules, implying their outspread bioapplications in cancer/gene therapy, biomedical application, and antimicrobial regulations. The state of supramolecular nanovalves could be well regulated by switching the conformation or the assembled/disassembled state of the assemblies. This tutorial review lays the foundation for a better understanding of the significant and typical intelligent drug-delivery systems immobilized with supramolecular polymers or supramolecular pseudorotaxanes as the gating entities of nanovalve-based molecular machines, by showing their chemical structures, operation modes, and release modalities triggered by various actuations at molecular scale. In particular, relevant perspectives of supramolecular therapeutics will also be elaborated upon.

To determine the optimal number of lymph nodes (LNs) examined and the role of adjuvant chemotherapy in stage I lung cancer.

The chlorine from HCl can be recycled by catalytic oxidation during the industrial process, but excessive heat will be produced during the HCl catalytic oxidation, which leads to catalyst deactivation. Thus, a study of the reaction kinetics of HCl catalytic oxidation over a Cu-based composite catalyst is necessary. The influence of Tvalues of 360–400 °C, nHCl/nO2values of 1–4, and FHCl0/Wvalues of 0.01–60 h–1on HCl conversion and reaction rate was studied, and a kinetic model was established by a MATLAB parameter fit and a statistical test. Results show that, before chemical equilibrium, HCl conversion and reaction rate increase with an increase in Tor a decrease in nHCl/nO2. With a decrease in FHCl0/W, HCl conversion increases while the HCl reaction rate decreases. After chemical equilibrium, HCl conversion decreases with an increase in Tand nHCl/nO2or a decrease in FHCl0/W. The kinetic model that assumes O2adsorption is the rate-controlling step can suitably describe the reaction behavior of HCl catalytic oxidation over a Cu-based composite catalyst.

To define the effects of Xanthoceras sorbifolia (EXS) on vascular inflammation and the mechanisms in endothelial cells.

This paper proposes a more accurate eccentricity and tilt measurement method based on Young’s interference experiment. The basic principle of the method is introduced first before the method is simulated. Then the results are obtained when a to-be-adjusted focusing lens with eccentricity and tilt is simulated. The optical sensitivity also is obtained from these simulation results, and the expression for the change in optical path length caused by eccentricity and tilt is analyzed. Use of this method to detect eccentricity and tilt and assist in adjustment of the system allows the instrument to achieve higher accuracy and thus obtain improved imaging quality and spectral resolution.

Membrane transporters can be major determinants of the pharmacokinetic profiles of anticancer drugs. The associations between genetic variations of ATP-binding cassette (ABC) and solute carrier (SLC) genes and cancer survival were investigated through a meta-analysis and an association study in the Seoul Breast Cancer Study (SEBCS). Including the SEBCS, the meta-analysis was conducted among 38 studies of genetic variations of transporters on various cancer survivors. The population of SEBCS consisted of 1338 breast cancer patients who had been treated with adjuvant chemotherapy. A total of 7750 SNPs were selected from 453 ABC and/or SLC genes typed by an Affymetrix 6.0 chip. ABCB1rs1045642 was associated with poor progression-free survival in a meta-analysis (HR = 1.33, 95% CI: 1.07–1.64). ABCB1, SLC8A1, and SLC12A8were associated with breast cancer survival in SEBCS (Pgene< 0.05). ABCB1rs1202172 was differentially associated with survival depending on the chemotherapy (Pinteraction= 0.035). Our finding provides suggestive associations of membrane transporters on cancer survival.

Iron-catalyzed conversion of coal/biomass-derived syngas directly to lower olefins through Fischer–Tropsch synthesis (i.e., FTO) is a sustainable and short-flow process. Herein, effects of Mn and K promoter loadings on FTO performance over the Fe-based catalyst supported on the promoter-adjustable carbon nanotubes (Fe/MnxKy-CNTs) are systematically studied. Several MnxKy-CNTs are prepared by the treatment of CNTs using aqueous KMnO4solution via a redox reaction, where promoter loadings are tailored by changing the aqueous KMnO4solution concentration and water amount for sample washing. FTO performance of these catalysts suggests that the increase in Mn and K loadings shows the enhanced lower olefins selectivity but suppressed activity. The resultant Fe/Mn16.5K1.2-CNTs exhibit the highest lower olefins yield. Further increasing K promoter content leads to slightly enhanced activity to lower olefins but dramatically suppressed CH4formation and enhanced chain growth. Moreover, appropriate precarburization temperature can facilitate the activity and selectivity toward lower olefins formation.

For any large weldment with many welding seams, the welding sequence and direction have a strong influence on the assembly and service performance, especially for the side beam of the bogie frame of a high-speed rail passenger car (CHR3; CRRC, Changchun, China). Because different combinations of the welding sequence and direction greatly increase the computational time and research costs, a three-dimensional finite element approach was developed to investigate the optimal welding sequence and direction. Then, a surrogate model was established by design of experiment and used the concepts of a pointer and stack. Finally, the welding sequence and direction were optimized by the discrete particle swarm optimization algorithm. The max residual deformation and stress of the optimal result were −3.92 mm and 212.56 MPa, respectively, which is approximately 22% and 38% lower than the traditional enterprise plan, respectively. Furthermore, a weighted form of the residual deformation and stress was proposed to the end of optimum comprehensive effect, and the result also had 11% and 28% reduction, respectively. The simulation result of the optimal plans well reproduced the theoretical distribution results of the residual deformation and stress. It is proven that the optimal result can improve the welding quality and process of the side beam weldment in production.

Dispersion equations of wave propagation in piezoelectric circular curved rods in an orthogonal curvilinear coordinate system are established in this paper, in which the displacements and electrical potential fields are described using Bessel functions. Characteristics of dispersion relations, distributions of displacements and electrical potential over the cross section are calculated. In the numerical examples, effects of various parameters on wave dispersions, distributions of displacement and electric potential of the first several modes over the cross section are investigated, in which influence of the changing of curvature radius of circular rods on distributions of displacement and electrical potential is compared, and also influence of whether considering the piezoelectric parameters in curved rods on dispersion is discussed.