Identification of key anti-neuroinflammatory components in Gastrodiae Rhizoma based on spectrum-effect relationships and its mechanism exploration.

Gastrodiae Rhizoma was proven to have anti-inflammatory activity based on its main component of 4-hydroxybenzyl alcohol (4-HBA) and gastrodin (GAS). However, the anti-inflammatory activity of other phenols has been less reported. In this study, the n-BuOH extract was selected as the active anti-inflammatory part of Gastrodiae Rhizoma based on the LPS-induced inflammatory BV-2 cells. The spectral-effect relationship analysis of the n-BuOH extract showed the main effective components were GAS, 4-HBA, parishin A (PA), parishin B (PB), and parishin C (PC). Among them, PB could reduce LPS-induced expression of nitric oxide (NO), intracellular ROS, TNF-α, IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Molecular docking predicted that PB had a good binding capacity to AMPKα and SIRT1 proteins of -12.1 kJ/mol and -7.6 kJ/mol, respectively. The Western Blot results further demonstrated that PB could inhibit NF-κB pathway by activating AMPK/SIRT1 pathway, thus exerting anti-LPS-induced neuroinflammatory effects. This study provides a referable idea for solving the problem of unclear action of TCM with complex compositions and is of great significance for the development of innovative medicines of traditional Chinese medicine.

Large Nonhysteretic Volume Magnetostriction in a Strong and Ductile High-Entropy Alloy.

Rapid development of smart technologies poses a big challenge for magnetostrictive materials, which should not only permit isotropic and hysteresis-free actuation (i.e., nonhysteretic volume change) in magnetic fields, but also have high strength and high ductility. Unfortunately, the magnetostriction from self-assembly of ferromagnetic domains is volume-conserving; the volume magnetostriction from field-induced first-order phase transition has large intrinsic hysteresis; and most prototype magnetostrictive materials are intrinsically brittle. Here, a magnetic high-entropy alloy (HEA) Fe35Co35Al10Cr10Ni10 is reported that can rectify these challenges, exhibiting an unprecedented combination of large nonhysteretic volume magnetostriction, high tensile strength and large elongation strain, over a wide working temperature range from room temperature down to 100 K. Its exceptional properties stem from a dual-phase microstructure, where the face-centered cubic (FCC) matrix phase with nanoscale compositional and structural fluctuations can enable a magnetic-field-induced transition from low-spin small-volume state to high-spin large-volume state, and the ordered body-centered cubic (BCC) B2 phase contributes to mechanical strengthening. The present findings may provide insights into designing unconventional and technologically important magnetostrictive materials.

Research trends and hotspot analysis of age-related hearing loss: A bibliometric analysis from 2019 to 2023.

BACKGROUND: Age-related hearing loss (ARHL) - also termed presbycusis - is prevalent among older adults, leading to a range of issues. Although considerable progress in the understanding of ARHL over the decades, available reports lack data from recent years and do not comprehensively reflect the latest advancements and trends. Therefore, our study sought to assess research hotspots and trends in ARHL over the past 5 years to provide the basis for future research. MATERIALS AND METHODS: The Web of Science Core Collection database was searched and screened from January 1, 2019 to October 21, 2023, according to the inclusion criteria. CiteSpace (5.8.R3), VOSviewer (1.6.19), and Microsoft Excel 2019 were employed for bibliometric analysis and visualization. RESULTS: 3084 articles from 92 countries led by the United States and China were included. There has been a steady upward trend in the number of publications from 2019 to 2023. The most productive institutions, authors, and journals are Johns Hopkins University (n = 113), Lin FR (n = 66), and Ear and Hearing (n = 135), respectively. Trend topic analyses revealed that "cochlear synaptopathy" and "dementia" were the predominant foci. Keywords, including "individuals" and "national health", began to appear. CONCLUSION: Over the past 5 years, the annual number of publications has increased significantly and will continue to do so. Research on the mechanism of ARHL, represented by "oxidative stress", is a continuing focus. Emerging topics such as "individual differences" and "national health" may be potential future hotspots in this field.

Potential for Recycling Metakaolin/Slag-Based Geopolymer Concrete of Various Strength Levels in Freeze-Thaw Conditions.

Geopolymer concrete (GPC) represents an innovative green and low-carbon construction material, offering a viable alternative to ordinary Portland cement concrete (OPC) in building applications. However, existing studies tend to overlook the recyclability aspect of GPC for future use. Various structural applications necessitate the use of concrete with distinct strength characteristics. The recyclability of the parent concrete is influenced by these varying strengths. This study examined the recycling potential of GPC across a spectrum of strength grades (40, 60, 80, and 100 MPa, marked as C40, C60, C80, and C100) when subjected to freeze-thaw conditions. Recycling 5-16 mm recycled geopolymer coarse aggregate (RGAs) from GPC prepared from 5 to 16 mm natural coarse aggregates (NAs). The cementitious material comprised 60% metakaolin and 40% slag, with natural gravel serving as the NAs, and the alkali activator consisting of sodium hydroxide solution and sodium silicate solution. The strength of the GPC was modulated by altering the Na/Al ratio. After 350 freeze-thaw cycles, the GPC specimens underwent crushing, washing, and sieving to produce RGAs. Subsequently, their physical properties (apparent density, water absorption, crushing index, and attached mortar content and microstructure (microhardness, SEM, and XRD) were thoroughly examined. The findings indicated that GPC with strength grades of C100, C80, and C60 were capable of enduring 350 freeze-thaw cycles, in contrast to C40, which did not withstand these conditions. RGAs derived from GPC of strength grades C100 and C80 complied with the criteria for Class II recycled aggregates, whereas RGAs produced from GPC of strength grade C60 aligned with the Class III level. A higher-strength grade in the parent concrete correlated with enhanced performance characteristics in the resulting recycled aggregates.

Deep learning-based detection of irreversible pulpitis in primary molars.

BACKGROUND: Changes in healthy and inflamed pulp on periapical radiographs are traditionally so subtle that they may be imperceptible to human experts, limiting its potential use as an adjunct clinical diagnostic feature. AIM: This study aimed to investigate the feasibility of an image-analysis technique based on the convolutional neural network (CNN) to detect irreversible pulpitis in primary molars on periapical radiographs (PRs). DESIGN: This retrospective study was performed in two health centres. Patients who received indirect pulp therapy at Peking University Hospital for Stomatology were retrospectively identified and randomly divided into training and validation sets (8:2). Using PRs as input to an EfficientNet CNN, the model was trained to categorise cases into either the success or failure group and externally tested on patients who presented to our affiliate institution. Model performance was evaluated using sensitivity, specificity, accuracy and F1 score. RESULTS: A total of 348 PRs with deep caries were enrolled from the two centres. The deep learning model achieved the highest accuracy of 0.90 (95% confidence interval: 0.79-0.96) in the internal validation set, with an overall accuracy of 0.85 in the external test set. The mean greyscale value was higher in the failure group than in the success group (p = .013). CONCLUSION: The deep learning-based model could detect irreversible pulpitis in primary molars with deep caries on PRs. Moreover, this study provides a convenient and complementary method for assessing pulp status.

Epigenetics and environmental health.

Epigenetic modifications including DNA methylation, histone modifications, chromatin remodeling, and RNA modifications complicate gene regulation and heredity and profoundly impact various physiological and pathological processes. In recent years, accumulating evidence indicates that epigenetics is vulnerable to environmental changes and regulates the growth, development, and diseases of individuals by affecting chromatin activity and regulating gene expression. Environmental exposure or induced epigenetic changes can regulate the state of development and lead to developmental disorders, aging, cardiovascular disease, Alzheimer's disease, cancers, and so on. However, epigenetic modifications are reversible. The use of specific epigenetic inhibitors targeting epigenetic changes in response to environmental exposure is useful in disease therapy. Here, we provide an overview of the role of epigenetics in various diseases. Furthermore, we summarize the mechanism of epigenetic alterations induced by different environmental exposures, the influence of different environmental exposures, and the crosstalk between environmental variation epigenetics, and genes that are implicated in the body's health. However, the interaction of multiple factors and epigenetics in regulating the initiation and progression of various diseases complicates clinical treatments. We discuss some commonly used epigenetic drugs targeting epigenetic modifications and methods to prevent or relieve various diseases regulated by environmental exposure and epigenetics through diet.

Identification of ClpB, a molecular chaperone involved in the stress tolerance and virulence of Streptococcus agalactiae.

Bacterial ClpB is an ATP-dependent disaggregate that belongs to the Hsp100/Clp family and facilitates bacterial survival under hostile environmental conditions. Streptococcus agalactiae, which is regarded as the major bacterial pathogen of farmed Nile tilapia (Oreochromis niloticus), is known to cause high mortality and large economic losses. Here, we report a ClpB homologue of S. agalactiae and explore its functionality. S. agalactiae with a clpB deletion mutant (∆clpB) exhibited defective tolerance against heat and acidic stress, without affecting growth or morphology under optimal conditions. Moreover, the ΔclpB mutant exhibited reduced intracellular survival in RAW264.7 cells, diminished adherence to the brain cells of tilapia, increased sensitivity to leukocytes from the head kidney of tilapia and whole blood killing, and reduced mortality and bacterial loads in a tilapia infection assay. Furthermore, the reduced virulence of the ∆clpB mutant was investigated by transcriptome analysis, which revealed that deletion of clpB altered the expression levels of multiple genes that contribute to the stress response as well as certain metabolic pathways. Collectively, our findings demonstrated that ClpB, a molecular chaperone, plays critical roles in heat and acid stress resistance and virulence in S. agalactiae. This finding provides an enhanced understanding of the functionality of this ClpB homologue in gram-positive bacteria and the survival strategy of S. agalactiae against immune clearance during infection.

Shenqi Fuzheng injection hinders non-small cell lung cancer cell growth by regulating the Bax/Bcl-2 signaling pathway.

INTRODUCTION: Lung cancer (LC) is the most common solid tumor and is currently considered the primary cause of cancer-related deaths worldwide. In clinical efficacy studies, it was not difficult to find that the combination of SFI and chemotherapy could improve the general condition of patients, reduce the side effects of chemotherapy drugs, and have a cooperative antitumor effect in NSCLC patients. However, whether SFI can be used as a novel antitumor drug is still unknown. METHODS: First, meta-analysis aimed to explore the efficacy of SFI in NSCLC patients, and SFI was identified by ultra-performance liquid chromatography‒mass spectrometry (UPLC‒MS). Cell proliferation, migration, and invasion were explored by Cell Counting Kit-8 (CCK-8), scratch healing, and Transwell assays, respectively. Cell cycle and apoptosis assays were performed by flow cytometry. Transcriptome sequencing analysis was performed in four NSCLC cell lines. Differential expression analysis was used to identify potential targets. Apoptosis-related protein levels were detected by Western blotting assays. The effects of SFI in NSCLC were further investigated by mouse xenografts. RESULTS: SFI could markedly improve the chemotherapy efficacy of NSCLC patients. The main active ingredients include flavonoids and terpenoids, which can effectively exert antitumor effects. SFI could not only inhibit tumor cell proliferation and cell migration/invasion but also regulate the cell cycle and promote tumor cell apoptosis. In NSCLC, SFI could enhance the transcription level of the CHOP gene, thereby upregulating the expression of the proapoptotic proteins Bax and caspase 3, and inhibiting the expression of the antiapoptotic protein Bcl-2. SFI hindered the growth of mouse NSCLC xenografts in vivo. CONCLUSIONS: SFI hindered tumor progression and might promote apoptosis by increasing the expression of Bax, caspase 3 and decreasing the level of Bcl-2 in NSCLC.

Enhancing the Mechanical and Durability Properties of Fully Recycled Aggregate Concrete Using Carbonated Recycled Fine Aggregates.

The global construction industry is increasingly utilizing concrete prepared from recycled aggregate as a substitute for natural aggregate. However, the subpar performance of recycled fine aggregate (RFA) has resulted in its underutilization, particularly in the structural concrete exposed to challenging environments, including those involving chlorine salts and freeze-thaw climates. This study aimed to enhance the performance of RFA as a substitute for river sand in concrete as well as fulfill the present demand for fine aggregates in the construction sector by utilizing accelerated carbonation treatment to create fully recycled aggregate concrete (FRAC) composed of 100% recycled coarse and fine aggregates. The impacts of incorporating carbonated recycled fine aggregate (C-RFA) at various replacement rates (0%, 25%, 50%, 75%, and 100%) on the mechanical and durability properties of FRAC were investigated. The results showed that the physical properties of C-RFA, including apparent density, water absorption, and crushing value, were enhanced compared to that of RFA. The compressive strength of C-RFC100 was 19.8% higher than that of C-RFC0, while the water absorption decreased by 14.6%. In a comparison of C-RFC0 and C-RFC100, the chloride permeability coefficients showed a 50% decrease, and the frost resistance increased by 27.6%. According to the findings, the mechanical and durability properties, the interfacial transition zones (ITZs), and micro-cracks of the C-RFC were considerably enhanced with an increased C-RFA content.

T-cell subsets and cytokines are indicative of neoadjuvant chemoimmunotherapy responses in NSCLC.

PURPOSE: Neoadjuvant PD-1 blockade combined with chemotherapy is a promising treatment for resectable non-small cell lung cancer (NSCLC), yet the immunological mechanisms contributing to tumor regression and biomarkers corresponding to different pathological responses remain unclear. METHODS: Using dynamic and paired blood samples from NSCLC patients receiving neoadjuvant chemoimmunotherapy, we analyzed the frequencies of CD8 + T-cell and Treg subsets and their dynamic changes during neoadjuvant treatment through flow cytometry. Cytokine profiles and function-related gene expression of CD8 + T cells and Tregs were analyzed through flow cytometry and mRNA-seq. Infiltrating T-cell subsets in resected tissues from patients with different pathological responses were analyzed through multiplex immunofluorescence. RESULTS: Forty-two NSCLC patients receiving neoadjuvant chemoimmunotherapy were enrolled and then underwent surgical resection and pathological evaluation. Nineteen patients had pCR (45%), 7 patients had MPR (17%), and 16 patients had non-MPR (38%). In patients with pCR, the frequencies of CD137 + CD8 + T cells (P = 0.0475), PD-1 + Ki-67 + CD8 + T cells (P = 0.0261) and Tregs (P = 0.0317) were significantly different from those of non-pCR patients before treatment. pCR patients usually had low frequencies of CD137 + CD8 + T cells, PD-1 + Ki-67 + CD8 + T cells and Tregs, and their AUCs were higher than that of tissue PD-L1 expression. Neoadjuvant chemoimmunotherapy markedly improved CD8 + T-cell proliferation and activation, especially in pCR patients, as the frequencies of CD137 + CD8 + (P = 0.0136) and Ki-67 + CD8 + (P = 0.0391) T cells were significantly increased. The blood levels of cytokines such as IL-2 (P = 0.0391) and CXCL10 (P = 0.0195) were also significantly increased in the pCR group, which is consistent with the high density of activated cytotoxic T cells at the tumor site (P < 0.0001). CONCLUSION: Neoadjuvant chemoimmunotherapy drives CD8 + T cells toward a proliferative and active profile. The frequencies of CD137 + CD8 + T cells, PD-1 + Ki-67 + CD8 + T cells and Tregs at baseline might predict the response to neoadjuvant chemoimmunotherapy in NSCLC patients. The increase in IL-2 and CXCL10 might reflect the chemotaxis and enrichment of cytotoxic T cells at the tumor site and a better response to neoadjuvant chemoimmunotherapy.

TMEM119 (c.G143A, p.S48L) Mutation Is Involved in Primary Failure of Eruption by Attenuating Glycolysis-Mediated Osteogenesis.

Primary failure of eruption (PFE) is a rare oral disease with an incidence rate of 0.06%. It is characterized by abnormal eruption mechanisms that disrupt tooth eruption. The underlying pathogenic genetic variant and mechanism of PFE remain largely unknown. The purpose of this study was to explore the role of a novel transmembrane protein 119 (TMEM119) mutation in two PFE patients in a Chinese family. Information collection was performed on the family with a diagnosis of PFE, and blood samples from patients and healthy family members were extracted. Whole-exome sequencing was performed. Bioinformatics analysis revealed that a heterozygous variant in the TMEM119 gene (c.G143A, p.S48L) was a disease-associated mutation in this family. Recombinant pcDNA3.1 plasmid-containing wild-type and mutant TMEM119 expression cassettes were successfully constructed and transfected into MC3T3-E1 cells, respectively. The results of in vitro analysis suggested that the subcellular distribution of the TMEM119 protein was transferred from the cell cytoplasm to the nucleus, and the ability of cells to proliferate and migrate as well as glycolytic and mineralized capacities were reduced after mutation. Furthermore, rescue assays showed that activating transcription factor 4 (ATF4) overexpression rescued the attenuated glycolysis and mineralization ability of cells. Results of in vivo analysis demonstrated that TMEM119 was mainly expressed in the alveolar bone around the mouse molar germs, and the expression level increased with tooth eruption, demonstrated using immunohistochemistry and immunofluorescence. Collectively, the novel TMEM119 mutation is potentially pathogenic in the PFE family by affecting the glucose metabolism and mineralized function of osteoblasts, including interaction with ATF4. Our findings broaden the gene mutation spectrum of PFE and further elucidate the pathogenic mechanism of PFE.

Protein-Integrated Hydrogen-Bonded Organic Frameworks: Chemistry and Biomedical Applications.

Hydrogen-bonded organic frameworks (HOFs) are porous nanomaterials that offer exceptional biocompatibility and versatility for integrating proteins for biomedical applications. This minireview concisely discusses recent advancements in the chemistry and functionality of protein-HOF interfaces. It particularly focuses on strategic methodologies, such as the careful selection of building blocks and the genetic engineering of proteins, to facilitate protein-HOF interactions. We examine the role of enzyme encapsulation within HOFs, highlighting its capability to preserve enzyme function, a crucial aspect for applications in biosensing and disease diagnosis. Moreover, we discuss the emerging utility of nanoscale HOFs for intracellular protein delivery, illustrating their applicability as nanoreactors for intracellular catalysis and neuroprotective biorthogonal catalysis within cellular compartments. We highlight the significant advancement of designing biodegradable HOFs tailored for cytosolic protein delivery, underscoring their promising application in targeted cancer therapies. Finally, we provide a perspective viewpoint on the design of biocompatible protein-HOF assemblies, underlining their promising prospects in drug delivery, disease diagnosis, and broader biomedical applications.

Efficient image reconstruction for a small animal PET system with dual-layer-offset detector design.

BACKGROUND: A compact PET/SPECT/CT system Inliview-3000B has been developed to provide multi-modality information on small animals for biomedical research. Its PET subsystem employed a dual-layer-offset detector design for depth-of-interaction capability and higher detection efficiency, but the irregular design caused some difficulties in calculating the normalization factors and the sensitivity map. Besides, the relatively larger (2 mm) crystal cross-section size also posed a challenge to high-resolution image reconstruction. PURPOSE: We present an efficient image reconstruction method to achieve high imaging performance for the PET subsystem of Inliview-3000B. METHODS: List mode reconstruction with efficient system modeling was used for the PET imaging. We adopt an on-the-fly multi-ray tracing method with random crystal sampling to model the solid angle, crystal penetration and object attenuation effect, and modify the system response model during each iteration to improve the reconstruction performance and computational efficiency. We estimate crystal efficiency with a novel iterative approach that combines measured cylinder phantom data with simulated line-of-response (LOR)-based factors for normalization correction before reconstruction. Since it is necessary to calculate normalization factors and the sensitivity map, we stack the two crystal layers together and extend the conventional data organization method here to index all useful LORs. Simulations and experiments were performed to demonstrate the feasibility and advantage of the proposed method. RESULTS: Simulation results showed that the iterative algorithm for crystal efficiency estimation could achieve good accuracy. NEMA image quality phantom studies have demonstrated the superiority of random sampling, which is able to achieve good imaging performance with much less computation than traditional uniform sampling. In the spatial resolution evaluation based on the mini-Derenzo phantom, 1.1 mm hot rods could be identified with the proposed reconstruction method. Reconstruction of double mice and a rat showed good spatial resolution and a high signal-to-noise ratio, and organs with higher uptake could be recognized well. CONCLUSION: The results validated the superiority of introducing randomness into reconstruction, and demonstrated its reliability for high-performance imaging. The Inliview-3000B PET subsystem with the proposed image reconstruction can provide rich and detailed information on small animals for preclinical research.

Unleashing the Power of Proenzyme Delivery for Targeted Therapeutic Applications Using Biodegradable Lipid Nanoparticles.

Proenzymes, functioning as inactive precursor forms of enzymes, hold significant promise for regulating essential biological processes. Their inherent property of latency, remaining inert until they arrive at the intended site of action, positions them as particularly promising candidates for the development of targeted therapeutics. Despite this potential, the therapeutic potential of proenzymes is challenged by designing proenzymes with excellent selectivity for disease cells. This limitation is further exacerbated by the inability of proenzymes to spontaneously cross the cell membrane, a biological barrier that impedes the cellular internalization of exogenous macromolecules. Therefore, efficacious intracellular delivery is paramount to unlocking the full therapeutic potency of proenzymes.In this Account, we first elucidate our recent advancements made in designing biodegradable lipid nanoparticles (LNPs) for the cell-specific delivery of biomacromolecules, including proteins and nucleic acids. Using a strategy of parallel synthesis, we have constructed an extensive library of ionizable lipids, each integrated with different biodegradable moieties. This combinatorial approach has led to the identification of LNPs that are particularly efficacious for the delivery of biomacromolecules specifically to tumor cells. This innovation capitalizes on the unique intracellular environment of cancer cells to control the degradation of LNPs, thereby ensuring the targeted release of therapeutics within tumor cells. Additionally, we discuss the structure-activity relationship governing the delivery efficacy of these LNPs and their applicability in regulating tumor cell signaling, specifically through the delivery of bacterial effector proteins.In the second segment, we aim to provide an overview of our recent contributions to the field of proenzyme design, where we have chemically tailored proteins to render them responsive to the unique milieu of tumor cells. Specifically, we elaborate on the chemical principles employed to modify proteins and DNAzymes, thereby priming them for activation in the presence of NAD(P)H:quinone oxidoreductase 1 (NQO1), an enzyme that is prevalently upregulated within tumor cells. We summarize the methodologies for intracellular delivery of these proenzymes using biodegradable LNPs, both in vitro and in vivo. The concomitant intracellular delivery and activation of proenzymes are examined in the context of enhanced therapeutic outcomes and targeted CRISPR/Cas9 genome editing.In conclusion, we offer a perspective on the chemical principles that could be leveraged to optimize LNPs for tissue-specific delivery of proenzymes. We also explore chemical strategies for the irreversible modulation of proenzyme activity within living cells and in vivo. Through this discussion, we provide insights into potential avenues for overcoming existing limitations and enhancing the delivery of proenzymes using LNPs, particularly for developing tumor-targeted therapies and genome editing applications.

The Impact of Inadequate Energy Intake on Readmission Burden of Patients With Heart Failure.

BACKGROUND: Adequate energy intake is essential for good clinical outcomes. The association between energy intake and readmission burden of patients with heart failure (HF) still needs to be clarified. OBJECTIVE: In this study, our aim was to determine the association between energy intake and readmission in patients with HF. METHODS: A total of 311 inpatients with HF were recruited. Demographic and clinical information were collected during hospitalization; the daily diets of the participants were collected in the second week after discharge using the 3-day diet record, and the energy intake was calculated using a standardized nutrition calculator. The inadequate energy intake was defined as <70% × 25 kcal/kg of ideal body weight. The participants were followed up for 12 weeks after discharge. The number, reasons, and length of stay of unplanned readmissions were collected. Regression analyses were used to evaluate the associations between inadequate energy intake, and readmission rate and readmission days. RESULTS: The median of the energy intake of participants was 1032 (interquartile range, 809-1266) kcal/d. The prevalence of inadequate energy intake was 40%. Patients with inadequate energy intake had a higher risk of unplanned readmission (odds ratio, 5.616; 95% confidence interval, 3.015-10.462; P < .001) and more readmission days (incidence rate ratio, 5.226; 95% confidence interval, 3.829-7.134, P < .001) after adjusting for potential confounders. CONCLUSIONS: Patients with HF had a high incidence of inadequate dietary energy intake, and it increases the burden of readmission.

An Ultraflexible Electrode Array for Large-Scale Chronic Recording in the Nonhuman Primate Brain.

Single-unit (SU) recording in nonhuman primates (NHPs) is indispensible in the quest of how the brain works, yet electrodes currently used for the NHP brain are limited in signal longevity, stability, and spatial coverage. Using new structural materials, microfabrication, and penetration techniques, we develop a mechanically robust ultraflexible, 1 µm thin electrode array (MERF) that enables pial penetration and high-density, large-scale, and chronic recording of neurons along both vertical and horizontal cortical axes in the nonhuman primate brain. Recording from three monkeys yields 2,913 SUs from 1,065 functional recording channels (up to 240 days), with some SUs tracked for up to 2 months. Recording from the primary visual cortex (V1) reveals that neurons with similar orientation preferences for visual stimuli exhibited higher spike correlation. Furthermore, simultaneously recorded neurons in different cortical layers of the primary motor cortex (M1) show preferential firing for hand movements of different directions. Finally, it is shown that a linear decoder trained with neuronal spiking activity across M1 layers during monkey's hand movements can be used to achieve on-line control of cursor movement. Thus, the MERF electrode array offers a new tool for basic neuroscience studies and brain-machine interface (BMI) applications in the primate brain.

Policy instruments facilitate China's COVID-19 work resumption.

Governments worldwide have announced stimulus packages to remobilize the labor force after COVID-19 and therefore to cope with the COVID-19-related recession. However, it is still unclear how to facilitate large-scale work resumption. This paper aims to clarify the issue by analyzing the large-scale prefecture-level dataset of human mobility trajectory information for 320 million workers and about 500,000 policy documents in China. We model work resumption as a collective behavioral change due to configurations of capacity, motivation, and policy instruments by using qualitative comparative analysis. We find that the effectiveness of post-COVID-19 recovery stimulus varied across China depending on the fiscal and administrative capacity and the policy motivation of the prefecture. Subnational fiscal and procurement policies were more effective for the wholesale and retail sector and the hotel and catering sector, whereas the manufacturing and business services sectors required more effort regarding employment policies. Due to limited prefectural capacity and wavering policy motivation, the simultaneous adoption of fiscal, employment, and procurement policy interventions endangered post-COVID-19 work resumption. We highlight the necessity of tailored postcrisis recovery strategies based on local fiscal and administrative capacity and the sectoral structure.

Rapid design of hybrid mechanism metasurface with random coding for terahertz dual-band RCS reduction.

In this paper, a hybrid mechanism metasurface (HMM) employing 1-bit random coding is proposed to achieve polarization-insensitive and dual-wideband monostatic/bistatic radar cross section (RCS) reduction under a wide range of incident angles. The anisotropic unit cell is designed by the combination of the multi-objective particle swarm optimization (MOPSO) algorithm and Python-CST joint simulation, which facilitates the rapid acquisition of the desired unit cell with excellent dual-band absorption conversion capability. The unit cell and its mirrored version are used to represent the units "0" and "1", respectively. In addition, the array distribution with random coding of the units "0" and "1" is optimized under different incident angles, polarizations and frequencies, which enables better diffusion-like scattering. Simulation results demonstrate that the proposed coding HMM can effectively reduce the monostatic/bistatic RCS by over 10 dB within the dual-band frequency ranges of 2.07-3.02 THz and 3.78-4.71 THz. Furthermore, the specular and bistatic RCS reduction performances remain stable at oblique incident angles up to 45° for both TE and TM polarizations.

JARID2 coordinates with the NuRD complex to facilitate breast tumorigenesis through response to adipocyte-derived leptin.

BACKGROUND: Proteins containing the Jumonji C (JmjC) domain participated in tumorigenesis and cancer progression. However, the mechanisms underlying this effect are still poorly understood. Our objective was to investigate the role of Jumonji and the AT-rich interaction domain-containing 2 (JARID2) - a JmjC family protein - in breast cancer, as well as its latent association with obesity. METHODS: Immunohistochemistry, The Cancer Genome Atlas, Gene Expression Omnibus, and other databases were used to analyze the expression of JARID2 in breast cancer cells. Growth curve, 5-ethynyl-2-deoxyuridine (EdU), colony formation, and cell invasion experiments were used to detect whether JARID2 affected breast cancer cell proliferation and invasion. Spheroidization-based experiments and xenotumor transplantation in NOD/SCID mice were used to examine the association between JARID2 and breast cancer stemness. RNA-sequencing, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis were used to identify the cell processes in which JARID2 participates. Immunoaffinity purification and silver staining mass spectrometry were conducted to search for proteins that might interact with JARID2. The results were further verified using co-immunoprecipitation and glutathione S-transferase (GST) pull-down experiments. Using chromatin immunoprecipitation (ChIP) sequencing, we sought the target genes that JARID2 and metastasis-associated protein 1 (MTA1) jointly regulated; the results were validated by ChIP-PCR, quantitative ChIP (qChIP) and ChIP-reChIP assays. A coculture experiment was used to explore the interactions between breast cancer cells and adipocytes. RESULTS: In this study, we found that JARID2 was highly expressed in multiple types of cancer including breast cancer. JARID2 promoted glycolysis, lipid metabolism, proliferation, invasion, and stemness of breast cancer cells. Furthermore, JARID2 physically interacted with the nucleosome remodeling and deacetylase (NuRD) complex, transcriptionally repressing a series of tumor suppressor genes such as BRCA2 DNA repair associated (BRCA2), RB transcriptional corepressor 1 (RB1), and inositol polyphosphate-4-phosphatase type II B (INPP4B). Additionally, JARID2 expression was regulated by the obesity-associated adipokine leptin via Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway in the breast cancer microenvironment. Analysis of various online databases also indicated that JARID2/MTA1 was associated with a poor prognosis of breast cancer. CONCLUSION: Our data indicated that JARID2 promoted breast tumorigenesis and development, confirming JARID2 as a target for cancer treatment.

Effects of weight loss in heart failure patients with overweight and obesity: a systematic review and meta-analysis.

AIMS: To perform a systematic review and meta-analysis to evaluate the impact of weight loss (WL) on the prognosis of overweight and obese patients with heart failure (HF). METHODS AND RESULTS: We reviewed the literature up to 1 February 2023 from PubMed, Web of Science, Embase, Cochrane Library, and Chinese databases for cohort studies, and randomized controlled trials (RCTs). Data from eligible studies were extracted, and statistical analyses were performed using Review Manager 5.3. A total of 19 studies (involving 449 882 patients) were included in the systematic review and meta-analyses. The results showed that WL did not reduce the mortality and rehospitalization rates in overweight and obese HF patients, but could improve the quality of life (P = 0.002), cardiac function (P = 0.0001), and exercise capacity (P = 0.03). The subgroup analysis showed that WL from bariatric surgery (BS) reduced the risk of death (P < 0.00001), WL from medication or exercise was not significantly associated with the risk of death (P = 0.18), and WL was associated with a higher mortality in the subgroup with unspecified WL modality or unintentional WL (P < 0.00001). In addition, it did not reduce the risk of short-term rehospitalization (P = 0.11), but reduced the rehospitalization rates over the long-term (P = 0.03). CONCLUSION: WL improves the long-term rehospitalization (>3 months), quality of life, cardiac function, and exercise capacity in overweight and obese HF patients. Although overall WL is not proven effective, subgroup analysis shows that BS can reduce mortality.

We used mortality, rehospitalization rates, quality of life, the New York Heart Association (NYHA), and 6-min walk test (6 MWT) to assess the impact of weight loss (WL) on the prognosis of overweight and obese heart failure (HF) patients. Key findings: WL is associated with improvements in long-term rehospitalization rates, quality of life, cardiac function, and exercise capacity.Bariatric surgery (BS) may reduce mortality in overweight and obese HF patients. Unintentional WL of more than 5% may mean a bad condition and could increase mortality.