Blood pressure targets, medication consideration and unique concerns in elderly hypertension IV: Focus on frailty, orthostatic hypotension, and resistant hypertension.

Hypertension increases the risk of cardiovascular disease in the elderly. Although treating hypertension can reduce the risk of cardiovascular disease and its related mortality, it is also challenging because these patients could have frailty, orthostatic hypotension (OH) and resistant hypertension (RHTN), which makes them more susceptible to treatment-related adverse events. Identifying such patients and tailoring the choice of drugs and blood pressure targets is crucial to balance the harms and benefits. The Clinical Frailty Scale is recommended to assess elderly patients with hypertension and frailty. For very frail patients, unnecessary medications should be deprescribed to avoid adverse events. Hypertension and OH frequently co-occur in the elderly, and recognizing and managing OH is essential to prevent falls and adverse events. The management of blood pressure in elderly patients with frailty, OH, and RHTN is complex, requiring the patients, their family and caregivers to be involved in decision-making to ensure that treatment plans are well-informed and aligned with the patient's needs.

Dual Orthogonally Polarized Lasing Assisted by Imaginary Fermi Arcs in Organic Microcavities.

The polarization control of micro- and nanolasers is an important topic in nanophotonics. Up to now, the simultaneous generation of two distinguishable orthogonally polarized lasing modes from a single organic microlaser remains a critical challenge. Here, we demonstrate simultaneously orthogonally polarized dual lasing from a microcavity filled with an organic single crystal exhibiting selective strong coupling. We show that the non-Hermiticity due to polarization-dependent losses leads to the formation of real and imaginary Fermi arcs with exceptional points. Simultaneous orthogonally polarized lasing becomes possible thanks to the eigenstate mixing by the photonic spin-orbit coupling at the imaginary Fermi arcs. Our work provides a novel way to develop linearly polarized lasers and paves the way for the future fundamental research in topological photonics, non-Hermitian optics, and other fields.

Microbial Upcycling of Depolymerized Lignin into Value-Added Chemicals.

Lignin is one of the most widespread organic compounds found on earth, boasting a wealth of aromatic molecules. The use of lignin feedstock for biochemical productions is of great importance for achieving "carbon neutrality." In recent years, a strategy for lignin valorization known as the "bio-funnel" has been proposed as a means to generate a variety of commercially valuable chemicals from lignin-derived compounds. The implementation of biocatalysis and metabolic engineering techniques has substantially advanced the biotransformation of depolymerized lignin into chemicals and materials within the supply chain. In this review, we present an overview of the latest advancements in microbial upcycling of depolymerized lignin into value-added chemicals. Besides, the review provides insights into the problems facing current biological lignin valorization while proposing further research directions to improve these technologies for the extensive accomplishment of the lignin upcycling.

Liquid crystal phase behavior of oxalated cellulose nanocrystal and optical films with controllable structural color induced by centripetal force.

Cellulose nanocrystal (CNC) is a sustainable bio-nanomaterial. The distinctive left-handed polarization properties render cellulose nanocrystal a promising candidate for optical film. Due to eco-friendliness, reliability, mildness and simplicity, the oxalate hydrolysis method stands out among various preparation methods for CNC. This study delved into the liquid crystal phase behavior of oxalated cellulose nanocrystal derived from pulp, and discovered the influences of CNC concentration and pH on suspension stability and phase transition, and evaluated its optical properties. The results demonstrated that oxalated CNC presented two different liquid crystal phases, the nematic phase and the cholesteric phase. The stability mechanism of CNC suspension and the regulatory principle of the liquid crystal phase transition were revealed. A novel CNC film-forming technology, the multilayer spin-coating technique, was developed for cellulose nanocrystal optical films. Driven by centrifugal force, cellulose nanocrystals were induced to self-assembly and formed the optical film with circular dichroism and structural color. This simple and efficient film-forming technology promised rapid processing (1 h) and controllable film structure and optical properties compared to traditional technologies. This work provided a theoretical understanding and practical prospects for integrating oxalated cellulose nanocrystal into sustainable advanced optical film materials.

Nanoscale ZnO doping in prosthetic polymers mitigate wear particle-induced inflammation and osteolysis through inhibiting macrophage secretory autophagy.

Wear particles produced by joint replacements induce inflammatory responses that lead to periprosthetic osteolysis and aseptic loosening. However, the precise mechanisms driving wear particle-induced osteolysis are not fully understood. Recent evidence suggests that autophagy, a cellular degradation process, plays a significant role in this pathology. This study aimed to clarify the role of autophagy in mediating inflammation and osteolysis triggered by wear particles and to evaluate the therapeutic potential of zinc oxide nanoparticles (ZnO NPs). We incorporated ZnO into the prosthetic material itself, ensuring that the wear particles inherently carried ZnO, providing a targeted and sustained intervention. Our findings reveal that polymer wear particles induce excessive autophagic activity, which is closely associated with increased inflammation and osteolysis. We identified secretory autophagy as a key mechanism for IL-1ß secretion, exacerbating osteolysis. Both in vitro and in vivo experiments demonstrated that ZnO-doped particles significantly inhibit autophagic overactivation, thereby reducing inflammation and osteolysis. In summary, this study establishes secretory autophagy as a critical mechanism in wear particle-induced osteolysis and highlights the potential of ZnO-doped prosthetic polymers for targeted, sustained mitigation of periprosthetic osteolysis.

Spin-Valley-Locked Electroluminescence for High-Performance Circularly Polarized Organic Light-Emitting Diodes.

Circularly polarized (CP) organic light-emitting diodes (OLEDs) have attracted attention in potential applications, including novel display and photonic technologies. However, conventional approaches cannot meet the requirements of device performance, such as high dissymmetry factor, high directionality, narrowband emission, simplified device structure, and low costs. Here, we demonstrate spin-valley-locked CP-OLEDs without chiral emitters but based on photonic spin-orbit coupling, where photons with opposite CP characteristics are emitted from different optical valleys. These spin-valley-locked OLEDs exhibit a narrowband emission of 16 nm, a high external quantum efficiency of 3.65%, a maximum luminance of near 98,000 cd/m2, and a gEL of up to 1.80, which are among the best performances of active single-crystal CP-OLEDs, achieved with a simple device structure. This strategy opens an avenue for practical applications toward three-dimensional displays and on-chip CP-OLEDs.

CRISPR-AMRtracker: A novel toolkit to monitor the antimicrobial resistance gene transfer in fecal microbiota.

The spread of antibiotic resistance genes (ARGs), particularly those carried on plasmids, poses a major risk to global health. However, the extent and frequency of ARGs transfer in microbial communities among human, animal, and environmental sectors is not well understood due to a lack of effective tracking tools. We have developed a novel fluorescent tracing tool, CRISPR-AMRtracker, to study ARG transfer. It combines CRISPR/Cas9 fluorescence tagging, fluorescence-activated cell sorting, 16S rRNA gene sequencing, and microbial community analysis. CRISPR-AMRtracker integrates a fluorescent tag immediately downstream of ARGs, enabling the tracking of ARG transfer without compromising the host cell's antibiotic susceptibility, fitness, conjugation, and transposition. Notably, our experiments demonstrate that sfGFP-tagged plasmid-borne mcr-1 can transfer across diverse bacterial species within fecal samples. This innovative approach holds the potential to illuminate the dynamics of ARG dissemination and provide valuable insights to shape effective strategies in mitigating the escalating threat of antibiotic resistance.

Detecting bioactive compound contents in Dancong tea using VNIR-SWIR hyperspectral imaging and KRR model with a refined feature wavelength method.

Hyperspectral imaging (HSI) provides opportunity for non-destructively detecting bioactive compounds contents of tea leaves and high detection accuracy require extracting effective features from the complex hyperspectral data. In this paper, we proposed a feature wavelength refinement method called interval band selecting-competitive adaptive reweighted sampling-fusing (IBS-CARS-Fusing) to extract feature wavelengths from visible-near-infrared (VNIR) and short-wave-near-infrared (SWIR) hyperspectral images. Combined with the proposed IBS-CARS-Fusing method, a kernel ridge regression (KRR) model was established to predict the contents of bioactive compounds including chlorophyll a, chlorophyll b, carotenoids, tea polyphenols, and amino acids in Dancong tea. It was revealed that the IBS-CARS-Fusing method can improve Rp2 of KRR model for these bioactive compounds by 4.77%, 4.60%, 6.74%, 15.52%, and 13.10%, respectively, and Rp2 of the model reached high values of 0.9500, 0.9481, 0.8946, 0.8882, and 0.8622. Additionally, a leaf compound mass per area thermal map was used to visualize the spatial distribution of the compounds.

SARS-CoV-2 variants divergently infect and damage cardiomyocytes in vitro and in vivo.

BACKGROUND: COVID-19 can cause cardiac complications and the latter are associated with poor prognosis and increased mortality. SARS-CoV-2 variants differ in their infectivity and pathogenicity, but how they affect cardiomyocytes (CMs) is unclear. METHODS: The effects of SARS-CoV-2 variants were investigated using human induced pluripotent stem cell-derived (hiPSC-) CMs in vitro and Golden Syrian hamsters in vivo. RESULTS: Different variants exhibited distinct tropism, mechanism of viral entry and pathology in the heart. Omicron BA.2 most efficiently infected and injured CMs in vitro and in vivo, and induced expression changes consistent with increased cardiac dysfunction, compared to other variants tested. Bioinformatics and upstream regulator analyses identified transcription factors and network predicted to control the unique transcriptome of Omicron BA.2 infected CMs. Increased infectivity of Omicron BA.2 is attributed to its ability to infect via endocytosis, independently of TMPRSS2, which is absent in CMs. CONCLUSIONS: In this study, we reveal previously unknown differences in how different SARS-CoV-2 variants affect CMs. Omicron BA.2, which is generally thought to cause mild disease, can damage CMs in vitro and in vivo. Our study highlights the need for further investigations to define the pathogenesis of cardiac complications arising from different SARS-CoV-2 variants.

Organic polaritonic light-emitting diodes with high luminance and color purity toward laser displays.

Achieving high-luminescence organic light-emitting devices (OLEDs) with narrowband emission and high color purity is important in various optoelectronic fields. Laser displays exhibit outstanding advantages in next-generation display technologies owing to their ultimate visual experience, but this remains a great challenge. Here, we develop a novel OLED based organic single crystals. By strongly coupling the organic exciton state to an optical microcavity, we obtain polariton electroluminescent (EL) emission from the polariton OLEDs (OPLEDs) with high luminance, narrow-band emission, high color purity, high polarization as well as excellent optically pumped polariton laser. Further, we evaluate the potential for electrically pumped polariton laser through theoretical analysis and provide possible solutions. This work provides a powerful strategy with a material-device combination that paves the way for electrically driven organic single-crystal-based polariton luminescent devices and possibly lasers.

COVID-19 vaccination: 2023 Taiwan Association of Gerontology and Geriatrics (TAGG) consensus statements.

The COVID-19 pandemic remains challenging due to the rapid evolution of the severe acute respiratory syndrome coronavirus 2. This article discusses recent findings on high-risk groups for COVID-19 mortality and morbidity, along with consensus statements from the 2023 Taiwan Association of Gerontology and Geriatrics (TAGG) meeting. It examines evidence on viral mutation mechanisms, emerging variants, and their implications for vaccination strategies. The article underscores advanced age, immunocompromised status, chronic medical conditions, occupational exposure, and socioeconomic disparities as significant risk factors for severe COVID-19 outcomes. TAGG's consensus emphasizes robust vaccination promotion, prioritizing elderly, and immunocompromised groups, individualized multi-dose regimens for immunocompromised patients, and simplified clinical guidelines. Discussions on global and regional recommendations for regular, variant-adapted boosters highlight the non-seasonal nature of COVID-19. Key agreements include escalating domestic preparedness, implementing vigorous risk-based vaccination, and adapting global guidelines to local contexts. Given ongoing viral evolution, proactive adjustment of vaccination policies is essential. Scientific consensus, tailored recommendations, and rapid knowledge dissemination are vital for optimizing COVID-19 protection among vulnerable groups in Taiwan. This article seeks to inform clinical practice and public health policy by summarizing expert-driven vaccination perspectives.

An experimental study of the heterogeneity and anisotropy of porcine meniscal ultimate tensile strength.

Characterizing the ultimate tensile strength (UTS) of the meniscus is critical in studying knee damage and pathology. This study aims to determine the UTS of the meniscus with an emphasis on its heterogeneity and anisotropy. We performed tensile tests to failure on the menisci of six month old Yorkshire pigs at a low strain rate. Specimens from the anterior, middle and posterior regions of the meniscus were tested in the radial and circumferential directions. Then the UTS was obtained for each specimen and the data were analyzed statistically, leading to a comprehensive view of the variations in porcine meniscal strength. The middle region has the highest average strength in the circumferential (43.3 ± 4.7 MPa) and radial (12.6 ± 2.2 MPa) directions. This is followed by the anterior and posterior regions, which present similar average values (about 34.0MPa) in circumferential direction. The average strength of each region in the radial direction is approximately one-fourth to one-third of the value in the circumferential direction. This study is novel as it is the first work to focus on the experimental methods to investigate the heterogeneity and anisotropy only for porcine meniscus.

Innovative Delivery System Combining CRISPR-Cas12f for Combatting Antimicrobial Resistance in Gram-Negative Bacteria.

Antimicrobial resistance poses a significant global challenge, demanding innovative approaches, such as the CRISPR-Cas-mediated resistance plasmid or gene-curing system, to effectively combat this urgent crisis. To enable successful curing of antimicrobial genes or plasmids through CRISPR-Cas technology, the development of an efficient broad-host-range delivery system is paramount. In this study, we have successfully designed and constructed a novel functional gene delivery plasmid, pQ-mini, utilizing the backbone of a broad-host-range Inc.Q plasmid. Moreover, we have integrated the CRISPR-Cas12f system into the pQ-mini plasmid to enable gene-curing in broad-host of bacteria. Our findings demonstrate that pQ-mini facilitates the highly efficient transfer of genetic elements to diverse bacteria, particularly in various species in the order of Enterobacterales, exhibiting a broader host range and superior conjugation efficiency compared to the commonly used pMB1-like plasmid. Notably, pQ-mini effectively delivers the CRISPR-Cas12f system to antimicrobial-resistant strains, resulting in remarkable curing efficiencies for plasmid-borne mcr-1 or blaKPC genes that are comparable to those achieved by the previously reported pCasCure system. In conclusion, our study successfully establishes and optimizes pQ-mini as a broad-host-range functional gene delivery vector. Furthermore, in combination with the CRISPR-Cas system, pQ-mini demonstrates its potential for broad-host delivery, highlighting its promising role as a novel antimicrobial tool against the growing threat of antimicrobial resistance.

Transmission Patterns of Co-Circulation of Omicron Sub-Lineages in Hong Kong SAR, China, a City with Rigorous Social Distancing Measures, in 2022.

OBJECTIVE: This study aimed to characterize the changing landscape of circulating SARS-CoV-2 lineages in the local community of Hong Kong throughout 2022. We examined how adjustments to quarantine arrangements influenced the transmission pattern of Omicron variants in a city with relatively rigorous social distancing measures at that time. METHODS: In 2022, a total of 4684 local SARS-CoV-2 genomes were sequenced using the Oxford Nanopore GridION sequencer. SARS-CoV-2 consensus genomes were generated by MAFFT, and the maximum likelihood phylogeny of these genomes was determined using IQ-TREE. The dynamic changes in lineages were depicted in a time tree created by Nextstrain. Statistical analysis was conducted to assess the correlation between changes in the number of lineages and adjustments to quarantine arrangements. RESULTS: By the end of 2022, a total of 83 SARS-CoV-2 lineages were identified in the community. The increase in the number of new lineages was significantly associated with the relaxation of quarantine arrangements (One-way ANOVA, F(5, 47) = 18.233, p < 0.001)). Over time, Omicron BA.5 sub-lineages replaced BA.2.2 and became the predominant Omicron variants in Hong Kong. The influx of new lineages reshaped the dynamics of Omicron variants in the community without fluctuating the death rate and hospitalization rate (One-way ANOVA, F(5, 47) = 2.037, p = 0.091). CONCLUSION: This study revealed that even with an extended mandatory quarantine period for incoming travelers, it may not be feasible to completely prevent the introduction and subsequent community spread of highly contagious Omicron variants. Ongoing molecular surveillance of COVID-19 remains essential to monitor the emergence of new recombinant variants.

Odorant receptor co-receptors affect expression of tuning receptors in Drosophila.

Insects detect odorants using two large families of heteromeric receptors, the Odorant Receptors (ORs) and Ionotropic Receptors (IRs). Most OR and IR genes encode odorant-binding "tuning" subunits, whereas four (Orco, Ir8a, Ir25a, and Ir76b) encode co-receptor subunits required for receptor function. Olfactory neurons are thought to degenerate in the absence of Orco in ants and bees, and limited data suggest this may happen to some olfactory neurons in Drosophila fruit flies as well. Here, we thoroughly examined the role of co-receptors on olfactory neuron survival in Drosophila. Leveraging knowledge that olfactory neuron classes are defined by the expression of different tuning receptors, we used tuning receptor expression in antennal transcriptomes as a proxy for the survival of distinct olfactory neuron classes. Consistent with olfactory neuron degeneration, expression of many OR-family tuning receptors is decreased in Orco mutants relative to controls, and transcript loss is progressive with age. The effects of Orco are highly receptor-dependent, with expression of some receptor transcripts nearly eliminated and others unaffected. Surprisingly, further studies revealed that olfactory neuron classes with reduced tuning receptor expression generally survive in Orco mutant flies. Furthermore, there is little apoptosis or neuronal loss in the antenna of these flies. We went on to investigate the effects of IR family co-receptor mutants using similar approaches and found that expression of IR tuning receptors is decreased in the absence of Ir8a and Ir25a, but not Ir76b. As in Orco mutants, Ir8a-dependent olfactory neurons mostly endure despite near-absent expression of associated tuning receptors. Finally, we used differential expression analysis to identify other antennal genes whose expression is changed in IR and OR co-receptor mutants. Taken together, our data indicate that odorant co-receptors are necessary for maintaining expression of many tuning receptors at the mRNA level. Further, most Drosophila olfactory neurons persist in OR and IR co-receptor mutants, suggesting that the impact of co-receptors on neuronal survival may vary across insect species.

Correction: Assessment of network structure characteristics and factors of corporate flows in Guangdong Province.

[This corrects the article DOI: 10.1371/journal.pone.0293870.].

Tobramycin-resistant small colony variant mutant of Salmonella enterica serovar Typhimurium shows collateral sensitivity to nitrofurantoin.

The increasing antibiotic resistance poses a significant global health challenge, threatening our ability to combat infectious diseases. The phenomenon of collateral sensitivity, whereby resistance to one antibiotic is accompanied by increased sensitivity to another, offers potential avenues for novel therapeutic interventions against infections unresponsive to classical treatments. In this study, we elucidate the emergence of tobramycin (TOB)-resistant small colony variants (SCVs) due to mutations in the hemL gene, which render S. Typhimurium more susceptible to nitrofurantoin (NIT). Mechanistic studies demonstrate that the collateral sensitivity in TOB-resistant S. Typhimurium SCVs primarily stems from disruptions in haem biosynthesis. This leads to dysfunction in the electron transport chain (ETC) and redox imbalance, ultimately inducing lethal accumulation of reactive oxygen species (ROS). Additionally, the upregulation of nfsA/B expressions facilitates the conversion of NIT prodrug into its active form, promoting ROS-mediated bacterial killing and contributing to this collateral sensitivity pattern. Importantly, alternative NIT therapy demonstrates a significant reduction of bacterial load by more than 2.24-log10 cfu/g in the murine thigh infection and colitis models. Our findings corroborate the collateral sensitivity of S. Typhimurium to nitrofurans as a consequence of evolving resistance to aminoglycosides. This provides a promising approach for treating infections due to aminoglycoside-resistant strains.

Identifications of novel host cell factors that interact with the receptor-binding domain of the SARS-CoV-2 spike protein.

SARS-CoV-2 entry into host cells is facilitated by the interaction between the receptor-binding domain of its spike protein (CoV2-RBD) and host cell receptor, ACE2, promoting viral membrane fusion. The virus also uses endocytic pathways for entry, but the mediating host factors remain largely unknown. It is also unknown whether mutations in the RBD of SARS-CoV-2 variants promote interactions with additional host factors to promote viral entry. Here, we used the GST pull-down approach to identify novel surface-located host factors that bind to CoV2-RBD. One of these factors, SH3BP4, regulates internalization of CoV2-RBD in an ACE2-independent but integrin- and clathrin-dependent manner and mediates SARS-CoV-2 pseudovirus entry, suggesting that SH3BP4 promotes viral entry via the endocytic route. Many of the identified factors, including SH3BP4, ADAM9, and TMEM2, show stronger affinity to CoV2-RBD than to RBD of the less infective SARS-CoV, suggesting SARS-CoV-2-specific utilization. We also found factors preferentially binding to the RBD of the SARS-CoV-2 Delta variant, potentially enhancing its entry. These data identify the repertoire of host cell surface factors that function in the events leading to the entry of SARS-CoV-2.

Cytoplasmic tail of transmembrane dscam controls antibacterial responses by regulating cell proliferation-related genes in hemocytes of Chinese mitten crab (Eriocheir sinensis).

In arthropods, the involvement of Dscam (Down syndrome cell adhesion molecule) in innate immunity has been extensively demonstrated. Its cytoplasmic tail contains multiple conserved functional sites, which indicates its involvement in different intracellular signaling pathways. In this study, we focused on the role of the cytoplasmic tail of Dscam in the Chinese mitten crab (Eriocheir sinensis) immune defense. In the group with cytoplasmic tail knockdown (the site was located on constant exons 37 and 38), 3885 differentially expressed genes (DEGs) were identified. The DEGs were enriched in small molecule binding, protein-containing complex binding, and immunity-related pathways. The expression of selected genes were validated using quantitative real-time reverse transcription PCR. We identified key Cell cycle, Janus kinase (JAK)-signal transducer, activator of transcription (STAT) and mitogen-activated protein kinase (MAPK) signaling pathway genes, the results indicated that the cytoplasmic tail of Dscam controls antibacterial responses by regulating cell proliferation-related genes in hemocytes.

The role of sirtuin1 in liver injury: molecular mechanisms and novel therapeutic target.

Liver disease is a common and serious threat to human health. The progression of liver diseases is influenced by many physiologic processes, including oxidative stress, inflammation, bile acid metabolism, and autophagy. Various factors lead to the dysfunction of these processes and basing on the different pathogeny, pathology, clinical manifestation, and pathogenesis, liver diseases are grouped into different categories. Specifically, Sirtuin1 (SIRT1), a member of the sirtuin protein family, has been extensively studied in the context of liver injury in recent years and are confirmed the significant role in liver disease. SIRT1 has been found to play a critical role in regulating key processes in liver injury. Further, SIRT1 seems to cause divers outcomes in different types of liver diseases. Recent studies have showed some therapeutic strategies involving modulating SIRT1, which may bring a novel therapeutic target. To elucidate the mechanisms underlying the role of sirtuin1 in liver injury and its potentiality as a therapeutic target, this review outlines the key signaling pathways associated with sirtuin1 and liver injury, and discusses recent advances in therapeutic strategies targeting sirtuin1 in liver diseases.