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Summary: Cell division is tightly regulated and requires an expanded energy supply. However, how this energy is generated remains unclear. Here, we establish a correlation between two mitochondrial Ca2+ influx events and ATP production during mitosis. While both events promote ATP production during mitosis, the second event, the Ca2+ influx surge, is substantial. To facilitate this Ca2+ influx surge, the lamin B receptor (LBR) organizes a mitosis-specific endoplasmic reticulum (ER)-mitochondrial contact site (ERMCS), creating a rapid Ca2+ transport pathway. LBR acts as a tether, connecting the ER Ca2+ release channel IP3R with the mitochondrial VDAC2. Depletion of LBR disrupts the Ca2+ influx surge, reduces ATP production, and postpones the metaphase-anaphase transition and subsequent cell division. These findings provide insight into the mechanisms underlying mitotic energy production and supply required for cell proliferation.

Pomegranate seeds (PS) are the dried seeds derived from pomegranate fruit, accounting for approximately 20% of the fruit’s total weight, and are a by-product of pomegranate juice extraction. These seeds hold significance in traditional medicine among Uyghurs and Tibetan cultures, featuring diverse clinical applications within traditional Chinese medicine. These applications include management of gastric coldness and acidity, abdominal distension, liver and gallbladder fever, and pediatric enteritis. PS demonstrates properties such as stomach tonicity, qi regulation, analgesia, and anti-inflammatory effects. Extensive research underscores the richness of PS in various phytochemical compounds and metabolites, notably unsaturated fatty acids (particularly linolenic acid and linoleic acid), phenolic compounds tocopherols, proteins, and volatile oils. Notably, among these bioactive compounds, punicic acid (PA), found within PS, demonstrates potential in the prevention and treatment of cancers, diabetes, obesity, and other ailments. Despite extensive literature on pomegranate as a botanical entity, a comprehensive review focusing specifically on the chemical composition and pharmacological effects of PS remains elusive. Therefore, this review aimed to consolidate knowledge regarding the medicinal properties of PS, summarizing its chemical composition, traditional uses, and pharmacological effects in treating various diseases, thereby laying a foundation for the advancement and application of PS in the field of pharmacology.

The purpose of this study is to use aeolian sand obtained from Inner Mongolia to partially replace quartz sand as fine aggregate to prepare 3D printed mortar to solve the scarcity problems of quartz sand resources in northwestern China. The mechanical properties tests (including flexural strength, compressive strength, tensile bond strength and axial compression tests) and frost resistance tests of cast specimens and printed mortar specimens in the X, Y and Z directions (abbreviated as CS, PS-X, PS-Y and PS-Z) were investigated. Furthermore, their microscopic morphology and pore structure parameters were compared and analyzed using scanning electron microscopy (SEM) and low field nuclear magnetic resonance (NMR), respectively. The results showed that the flexural strength and compressive strength of the samples following the inclined cross-path were superior to those following the Z-shaped path specimens. The tensile bonding strength of the CS, PS-X, PS-Y and PS-Z exhibited that F3 > F3X > F3Z > F3Y, and the peak stress was observed as F4X > F4 > F4Z > F4Y. This was attributed to the cement hydration of CS and PS-X being more sufficient than those of PS-Y and PS-Z. Furthermore, freezing-thawing cycles accelerated the degradation of aeolian sand 3D printed mortar specimens, increased their weight loss rate and porosities, as well as reduced relative dynamic modulus of elasticity. The porosities of specimens were as follows: PS-Y > PS-Z > PS-X > CS, and the porosity of PS-Y was 97.62 %, 36.07 % and 10.67 % higher than those of CS, PS-X and PS-Z, respectively. The significance of this research is to provide technical guidance and basis for the application of aeolian sand in 3D printed mortar in the future.

Abstract Background Chimeric antigen receptor macrophage (CAR-M) therapy is a novel cancer immunotherapy approach that integrates CAR structure and macrophage functions. CAR-M therapy has shown unique and impressive antitumor effects in immunotherapy for solid tumors. However, the polarization state of macrophages can affect the antitumor effect of CAR-M. We hypothesized that the antitumor activity of CAR-Ms may be further improved after inducing M1-type polarization. Methods In this report, we constructed a novel HER2-targeting CAR-M, which was composed of humanized anti-HER2 scFv, CD28 hinge region and FcγRI transmembrane domain and intracellular domain. Phagocytosis, tumor-killing capacities, and cytokine release of CAR-Ms were detected with or without M1-polarization pretreatment. Several syngeneic tumor models were used to monitor the in vivo antitumor activity of M1-polarized CAR-Ms. Results After polarization with LPS combined with interferon-γ in vitro, we found that the phagocytic and tumor-killing capacities of CAR-Ms against target cells were significantly enhanced. The expression of costimulatory molecules and proinflammatory cytokines was also significantly increased after polarization. By establishing several syngeneic tumor models in vivo, we also demonstrated that infusing polarized M1-type CAR-Ms could effectively suppress tumor progression and prolong the survival of tumor-bearing mice with enhanced cytotoxicity. Conclusions We demonstrated that our novel CAR-M can effectively eliminate HER2-positive tumor cells both in vitro and in vivo, and M1 polarization significantly enhanced the antitumor ability of CAR-M, resulting in a stronger therapeutic effect in solid cancer immunotherapy.

In this paper, to solve the previous instability of nitrate rust inhibitors, and their environmental hazards, the rust inhibition performance of green and environmentally friendly triethanolamine and water-soluble imidazoline rust inhibitor was studied under simulated pore solution conditions. The corrosion of steel bars was evaluated by electrochemical and dry-wet cycle tests of carbon steel sheets, and characterization was done by scanning electron microscopy (SEM). Triethanolamine and water-soluble imidazoline rust inhibitors could effectively inhibit the rapid development of carbon steel rust in the composite salt environment. When the dosage ratio was 4:6, the electrochemical impedance of the carbon steel sheet increased, the potential increased, the corrosion current density decreased, the mass loss rate decreased, the surface texture of the carbon steel was clear, and the thickness of the rust product was almost zero. The adsorption mold formed by the organic rust inhibitor made the harmful ions impenetrable, and the rust inhibition effect was optimal.

BackgroundTransitional care is a critical area of care delivery for older adults with chronic illnesses and complex health conditions. Older adults have high, ongoing care needs during the transition from hospital to home due to certain physical, psychological, social, and caregiving burdens, and in practice, patients' needs are not being met or are receiving transitional care services that are unequal and inconsistent with their actual needs, hindering their safe, healthy transition. The purpose of this study was to explore the perceptions of older adults and health care providers, including older adults, about the transition of care from hospital to home for older patients in one region of China.ObjectiveTo explore barriers and facilitators in the transition of care from hospital to home for older adults in China from the perspectives of older patients with chronic diseases and healthcare professionals.MethodsThis was a qualitative study based on a semi-structured approach. Participants were recruited from November 2021 to October 2022 from a tertiary and community hospital. Data were analyzed using thematic analysis.ResultsA total of 20 interviews were conducted with 10 patients and 9 medical caregivers, including two interviews with one patient. The older adult/adults patients included 4 men and 6 women with an age range of 63 to 89 years and a mean age of 74.3 ± 10.1 years. The medical caregivers included two general practitioners and seven nurses age range was 26 to 40 years with a mean age of 32.8 ± 4.6 years. Five themes were identified: (1) attitude and attributes; (2) better interpersonal relationships and communication between HCPs and patients; (3) improved Coordination of Healthcare Services Is Needed; (4) availability of resources and accessibility of services; and (5) policy and environment fit. These themes often serve as both barriers and facilitators to older adults' access to transitional care.ConclusionsGiven the fragmentation of the health care system and the complexity of care needs, patient and family-centered care should be implemented. Establish interconnected electronic information support systems; develop navigator roles; and develop competent organizational leaders and appropriate reforms to better support patient transitions.

Low accumulation and penetration of nanomedicines in tumor severely reduce therapeutic efficacy. Herein, a pH-responsive gold nanoassembly is designed to overcome these problems. Polyethylene glycol linked raltitrexed (RTX, target ligand and chemotherapy drug) and two tertiary amine molecules (1-(2-aminoethyl) pyrrolidine and N, N-dibutylethylenediamine) are modified on the surface of the 6-nm gold nanoparticles by lipoic acid to form gold nanoassembly defined as Au-NNP(RTX). The Au-NNP (RTX) nanoassembly could remain at about 160 nm at the blood circulation (pH 7.4), while split into 6-nm gold nanoparticles due to tertiary amine protonation at tumor extracellular pH (pH 6.8). This pH-responsive disassembly behavior endows Au-NNP(RTX) better tumor tissue permeability through the better diffusion brought by the size reduction. Meanwhile, after disassembly, more RTXs on the surface of gold nanoparticles are exposed from the shielded state of assembly along with 2.25-fold augment of cellular uptake capability. Most importantly, the results show that Au-NNP(RTX) possesses of high tumor accumulation and effective tumor penetration, thereby enhancing the tumor chemo-radiotherapy efficiency.

BackgroundChronic diseases are long-term, recurring and prolonged, requiring frequent travel to and from the hospital, community, and home settings to access different levels of care. Hospital-to-home transition is challenging travel for elderly patients with chronic diseases. Unhealthy care transition practices may be associated with an increased risk of adverse outcomes and readmission rates. The safety and quality of care transitions have gained global attention, and healthcare providers have a responsibility to help older adults make a smooth, safe, and healthy transition.ObjectiveThis study aims to provide a more comprehensive understanding of what may shape health transitions in older adults from multiple perspectives, including older chronic patients, caregivers, and healthcare providers.MethodsSix databases were searched during January 2022, including Pubmed, web of science, Cochrane, Embase, CINAHL (EBSCO), and PsycINFO (Ovid). The qualitative meta-synthesis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. The quality of included studies was appraised using the Critical Appraisal Skills Programme (CASP) qualitative research appraisal tool. A narrative synthesis was conducted informed by Meleis's Theory of Transition.ResultsSeventeen studies identified individual and community-focused facilitators and inhibitors mapped to three themes, older adult resilience, relationships and connections, and uninterrupted care transfer supply chain.ConclusionThis study identified potential transition facilitators and inhibitors for incoming older adults transitioning from hospital to home, and these findings may inform the development of interventions to target resilience in adapting to a new home environment, and human relations and connections for building partnerships, as well as an uninterrupted supply chain of care transfer at hospital-home delivery.Systematic review registrationwww.crd.york.ac.uk/prospero/, identifier: CRD42022350478.

Mitotic spindle assembly is required for proper cell division, but many underlying mechanisms remain unclear. Here, the authors show that NuMa undergoes liquid-liquid phase separation, condensing on spindle poles during mitotic entry and enriching critical components to promote spindle assembly.

Detailed information on system operation is recorded by system logs, from which fast and accurate detection of anomalies is conducive to service management and system maintenance. Log anomaly detection methods often only handle a single type of anomaly, and the utilization of log messages could be higher, which makes it challenging to improve the performance of log anomaly detection models. This article presents the LTAnomaly model to accomplish log anomaly detection using semantic information, sequence relationships, and component values to make a vector representation of logs, and we add Transformer with long short-term memory (LSTM) as our final classification model. When sequences are processed sequentially, the model is also influenced by the information from the global information, thus increasing the dependence on feature information. This improves the utilization of log messages with a flexible, simple, and robust model. To evaluate the effectiveness of our method, experiments are performed on the HDFS and BGL datasets, with the F1-measures reaching 0.985 and 0.975, respectively, showing that the proposed method enjoys higher accuracy and a more comprehensive application range than existing models.

Intracellular delivery enables the efficient drug delivery into various types of cells and has been a long-term studied topics in modern biotechnology. Targeted delivery with improved delivery efficacy requires considerable requirements. This process is a critical step in many cellular-level studies, such as cellular drug therapy, gene editing delivery, and a series of biomedical research applications. The emergence of micro- and nanotechnology has enabled the more accurate and dedicated intracellular delivery, and it is expected to be the next generation of controlled delivery with unprecedented flexibility. This review focuses on several represented micro- and nanoscale physical approaches for cell membrane disruption-based intracellular delivery and discusses the mechanisms, advantages, and challenges of each approach. We believe that the deeper understanding of intracellular delivery at such low dimension would help the research community to develop more powerful delivery technologies for biomedical applications. Keywords: Drug delivery, Physical approaches, Cell membrane disruption, Low dimension

Effective log anomaly detection can help operators locate and solve problems quickly, ensure the rapid recovery of the system, and reduce economic losses. However, recent log anomaly detection studies have shown some drawbacks, such as concept drift, noise problems, and fuzzy feature relation extraction, which cause data instability and abnormal misjudgment, leading to significant performance degradation. This paper proposes a multi-feature deep fusion of an unstable log anomaly detection model (MDFULog) for the above problems. The MDFULog model uses a novel log resolution method to eliminate the dynamic interference caused by noise. This paper proposes a feature enhancement mechanism that fully uses the correlation between semantic information, time information, and sequence features to detect various types of log exceptions. The introduced semantic feature extraction model based on Bert preserves the semantics of log messages and maps them to log vectors, effectively eliminating worker randomness and noise injection caused by log template updates. An Informer anomaly detection classification model is proposed to extract practical information from a global perspective and predict outliers quickly and accurately. Experiments were conducted on HDFS, OpenStack, and unstable datasets, showing that the anomaly detection method in this paper performs significantly better than available algorithms.

In this study, high-carbon ferrochrome slag powder produced by grinding was used to replace different proportions of cement, and the effect of the amount of ferrochrome slag powder on the physical and mechanical properties of ferrochrome-slag-cement composites was analyzed. Water-cooled ferrochrome slag with a particle size of 5 mm was used to completely replace coarse aggregate to prepare ferrochrome-slag-based concretes. The microstructure of ferrochrome-slag-cement composites was analyzed by X-ray diffraction, scanning electron microscopy, and thermogravimetry–differential scanning calorimetry analysis. The compressive strength, water absorption, and aggregate–slurry interface bonding properties of ferrochrome-slag-based concrete were studied. The results demonstrate that a ferrochrome slag powder amount of 15% leads to the highest performance of ferrochrome-slag-cement composite material, and the fluidity ratio of ferrochrome-slag-cement mortar is 103, higher than reference samples. Furthermore, the compressive strengths of ferrochrome slag concretes are 15.8% and 3.6% higher than conventional concrete, and the water absorption of ferrochrome slag low-carbon concrete is better than that of conventional concrete. The interface bonding structure between concrete aggregate and slurry was optimized. This research can provide a reference for studying the application of ferrochrome slag, both the feasibility of high-carbon ferrochrome slag powder as supplementary cementitious material and the application of ferrochrome slag as concrete aggregate, and it can help to achieve the purpose of saving energy and reducing carbon emissions.

Abstract Hydrodynamic force loading platforms for controllable cell mechanical deformation play an essential role in modern cell technologies. Current systems require assistance from specific microstructures thus limiting the controllability and flexibility in cell shape modulation, and studies on real‐time 3D cell morphology analysis are still absent. This article presents a novel platform based on acoustic streaming generated from a gigahertz device for cell shape control and real‐time cell deformation analysis. Details in cell deformation and the restoration process are thoroughly studied on the platform, and cell behavior control at the microscale is successfully achieved by tuning the treating time, intensity, and wave form of the streaming. The application of this platform in cell membrane permeability modulation and analysis is also exploited. Based on the membrane reorganization during cell deformation, the effects of deformation extent and deformation patterns on membrane permeability to micro‐ and macromolecules are revealed. This technology has shown its unique superiorities in cell mechanical manipulation such as high flexibility, high accuracy, and pure fluid force operation, indicating its promising prospect as a reliable tool for cell property study and drug therapy development.

Abstract Nanoparticles have long been one of the most popular delivery systems for enhancing the stability of therapeutic agents, providing targeted drug transportation, sustaining drug concentration at sites of action, and promoting therapeutic efficacy. Chitosan‐based nanoparticles have been widely explored as drug delivery systems due to the unique biological properties, such as easy to chemical modifications, biocompatibility, mucoadhesive feature, and absorption enhancement. In this review, we outline the biological properties and stimuli‐sensitive strategies of chitosan‐based self‐assembled nanoparticles as well as the recent developments in various applications in drug delivery, including cancer treatment, oral administration, skin regeneration, nasal/ocular mucosal administration, and pulmonary drug delivery. Chitosan‐based nanoparticles exhibit excellent features as drug delivery systems due to the outstanding biological properties. As the suitable vehicles for drug administration, chitosan‐based nanoparticles facilitate and improve drug bioavailability in all cases.

Epimedium herb is one of the most vital traditional Chinese medicines (TCMs), which is used for “nourishing the kidney and reinforcing the Yang”. In the guidance of TCM theory, Epimedium herb is usually processed with lamb oil to increase its efficacy. The contents of active ingredients in different Epimedium are significantly varied, which may derive from their different species, regions and processing methods. In this research, 13 batches of raw Epimedium collected from 6 provinces were identified. After optimization of the processing method of Epimedium, a liquid chromatography–mass spectrometry (LC–MS/MS) method for simultaneous determination of 16 compounds was established to evaluate the quality of raw and processed. Then the multivariate statistical technique was applied to compare different batches of Epimedium based on the LC–MS/MS data. As a conclusion, the herbs collected from 6 areas were ascribed to 5 species by microscopic and appearance features. Meanwhile, all of the raw and processed samples were classified by partial least squares discriminant analysis (PLS-DA) based on the 16 analyzed compounds. The comparison results indicate that processing and species both have important influences on Epimedium compositions contents.

A rapid and reliable HPLC-MS/MS method has been developed and validated for the simultaneous quantification of twelve bioactive compounds (baohuoside II, baohuoside I, sagittatoside A, sagittatoside B, magnoflorine, epimedin A, epimedin B, epimedin C, chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid and icariin) in rat plasma. The collected plasma samples were prepared by protein precipitate with acetonitrile. The twelve compounds were separated on a CORTECS®C18 column (4.6 mm × 150 mm, 2.7 μm) with a gradient mobile phase system of 0.1% (v/v) formic acid and acetonitrile at a flow rate of 0.3 mL/min. All of the analytes were quantitated using electrospray ionization (ESI) in negative ion mode with selected reaction monitoring (SRM). The intra- and inter-day accuracy ranged from −5.6% to 13.0%, and the precisions of the analytes were less than 10.9%. The mean recoveries of the analytes were in the range of 60.66% to 99.77% and the matrix effect ranged from 93.08% to 119.84%. Stability studies proved that the analytes were stable under the tested conditions, with a relative standard deviation (RSD) lower than 11.7%. The developed method was successfully applied to evaluating the pharmacokinetic study of twelve bioactive compounds after oral administration of Epimedium extract in rat.

The obstacles in the widespread application of -transaminases for the production of chiral amines is inefficient equilibrium displacement and high costs of by-product removal. Hence, our study skillfully designed a two-enzyme cascade methodology that eliminates the requirement of costly NAD(P)H resources. By incorporating a suitable carbonyl reductase within an optimal pH range coinciding with the ω-transaminase to facilitate transamination, this innovative process makes it possible to remove coproducts via asymmetric reduction with the assistance of carbonyl reductase. Two chiral compounds are obtained by the addition of the desired chiral amines. The carbonyl reductase has three distinct functions: providing extra chiral alcohols and amines, removing coproducts from the reaction system, and shifting the equilibrium towards the product formation side. The establishment of this cascade can also serve as a blueprint for subsequent enzymatic processes involving internal thermal equilibria. [ABSTRACT FROM AUTHOR]

Precise chromosome congression and segregation requires the proper assembly of a steady-state metaphase spindle, which is dynamic and maintained by continuous microtubule flux. NuSAP is a microtubule-stabilizing and -bundling protein that promotes chromosome-dependent spindle assembly. However, its function in spindle dynamics remains unclear. Here, we demonstrate that NuSAP regulates the metaphase spindle length control. Mechanistically, NuSAP facilitates kinetochore capture and spindle assembly by promoting Eg5 binding to microtubules. It also prevents excessive microtubule depolymerization through interaction with Kif2A, which reduces Kif2A spindle-pole localization. NuSAP is phosphorylated by Aurora A at Ser-240 during mitosis, and this phosphorylation promotes its interaction with Kif2A on the spindle body and reduces its localization with the spindle poles, thus maintaining proper spindle microtubule flux. NuSAP knockout resulted in the formation of shorter spindles with faster microtubule flux and chromosome misalignment. Taken together, we uncover that NuSAP participates in spindle assembly, dynamics, and metaphase spindle length control through the regulation of microtubule flux and Kif2A localization. [ABSTRACT FROM AUTHOR]