Management of a nursing unit in a COVID-19 shelter hospital in China: A case study.

OBJECTIVE: Fangcang shelter hospital is a form of large temporary hospital developed in China to tackle public health events. Through the case study and analysis of managing a nursing unit in a huge Fangcang shelter hospital transformed from the National Exhibition and Convention Center during the Omicron wave in Shanghai, China between April 9, 2022 and May 24, 2022, this paper aimed to highlight critical implications of public health nurses in health emergencies. DESIGN: A case study was conducted using data collected from a nursing unit with 570 beds. The five characteristics of management were organized as follows: human resource management, establishment and optimization of the core workflow, safety management of high-risk patients, the grid cooperation mechanism with patient volunteers, as well as humanistic nursing. RESULTS: Analysis of the data of the nursing unit indicated close team cooperation, efficient and orderly process scheduling, good outcomes of patients, and the indispensable role of volunteers. CONCLUSION: Practice indicated that nursing unit management in a large Fangcang shelter hospital is important to ensure medical order and efficiency. This practical experience can provide valuable reference and data to support for the nursing management of large-scale public health events, such as infectious disease epidemics.

A common thalamic hub for general and defensive arousal control.

The expression of defensive responses to alerting sensory cues requires both general arousal and a specific arousal state associated with defensive emotions. However, it remains unclear whether these two forms of arousal can be regulated by common brain regions. We discovered that the medial sector of the auditory thalamus (ATm) in mice is a thalamic hub controlling both general and defensive arousal. The spontaneous activity of VGluT2-expressing ATm (ATmVGluT2+) neurons was correlated with and causally contributed to wakefulness. In sleeping mice, sustained ATmVGluT2+ population responses were predictive of sensory-induced arousal, the likelihood of which was markedly decreased by inhibiting ATmVGluT2+ neurons or multiple downstream pathways. In awake mice, ATmVGluT2+ activation led to heightened arousal accompanied by excessive anxiety and avoidance behavior. Notably, blocking their neurotransmission abolished alerting stimuli-induced defensive behaviors. These findings may shed light on the comorbidity of sleep disturbances and abnormal sensory sensitivity in specific brain disorders.

Neuronal regulation of B-cell immunity: Anticipatory immune posturing?

The brain may sense, evaluate, modulate, and intervene in the operation of immune system, which would otherwise function autonomously in defense against pathogens. Antibody-mediated immunity is one arm of adaptive immunity that may achieve sterilizing protection against infection. Lymphoid organs are densely innervated. Immune cells supporting the antigen-specific antibody response express receptors for neurotransmitters and glucocorticoid hormones, and they are subjected to collective regulation by the neuroendocrine and the autonomic nervous system. Emerging evidence reveals a brain-spleen axis that regulates antigen-specific B cell responses and antibody-mediated immunity. In this article, we provide a synthesis of those studies as pertinent to neuronal regulation of B cell responses in secondary lymphoid organs. We propose the concept of defensive immune posturing as a brain-initiated top-down reaction in anticipation of potential tissue injury that requires immune protection.

Frequency-Bessel Transform Based Microtremor Survey Method and Its Engineering Application.

The development and utilization of urban underground space depend heavily on an understanding of urban geological conditions. The microtremor survey method is essential in urban geological surveys due to its quickness, convenience, non-destructiveness, and interference resistance. Since only the fundamental dispersion curves of Rayleigh waves can be obtained by utilizing the spatial autocorrelation method, the inversion results have multiple solutions. To improve the accuracy of the microtremor survey, this study employed the frequency-Bessel transform to extract the fundamental and higher modes of dispersion information of Rayleigh waves from the microtremor data array and verified the effectiveness of this method by synthesizing theoretical microtremor signals. Additionally, taking into account the order identification challenges brought on by mode jumps or missing modes in the dispersion curve, this study processed a multi-mode dispersion curve based on the newly proposed inversion objective function coupled with a genetic algorithm to obtain a shallow surface S-wave velocity structure. Compared to the traditional inversion objective function, the new function presented in this study could address mode misidentification more effectively and improved the accuracy of inversion calculations. Finally, the applicability and dependability of the frequency-Bessel-transform-based microtremor survey method were evaluated in a practical engineering case.

Optimization and Fabrication of MEMS suspended structures for nanoscale thermoelectric devices.

By eliminating the influence of the substrate on parasitic thermal resistance, MEMS suspended structures become one of the accurate nanoscale thermoelectric performance evaluation devices. However, the process of MEMS suspended thermoelectric devices is complex, and its multilayer suspended structure is easy to fracture due to large stress. As a result, optimizing the design of suspended structures is critical in order to reduce manufacturing complexity and increase yield. In this study, finite element simulation is used to investigate the impacts of varying structures and sizes on the stress of MEMS suspended devices. The maximum stress and average stress of silicon nanomaterials are lowered by 90.89% and 92.35%, respectively, by optimizing the structure and size of the beams and nanobelt. Moreover, MEMS suspended devices of various structures are successfully manufactured. It not only increases the yield to more than 70% but also decreases the impact of strain on thermoelectric performance and can be used to create suspended devices with integrated silicon microstrips.

Future changes in the intensity and frequency of precipitation extremes over China in a warmer world: Insight from a large ensemble.

Sufficient samples of extreme precipitation events are needed in order to obtain reliable estimates of the probability of their occurrence. Here, we use a large ensemble simulation with 50 members from the Canadian Earth System Model (CanESM2) under the representative concentration pathway 8.5 (RCP8.5) scenario to give future projection of the intensity and frequency of extreme precipitation events under different warming levels relative to the current climate over China. A bias-correction method based on quantile mapping is first used to remove systematic biases in the ensemble. The return value and return period are obtained by fitting enough annual maximum precipitation samples with the generalized extreme value to represent the intensity and frequency of extreme events, respectively. The results show that the average intensity of extreme precipitation in China will increase by nearly 8% per 1°C of global warming, which closely follows the Clausius-Clapeyron relation. Rarer extreme events will experience greater changes in frequency, especially under higher warming. The nationally averaged extreme precipitation events, presently expected to occur every 50 years (100 years) under the current climate conditions, are expected to occur approximately every 41 years (82 years), 32 years (62 years), 22 years (42 years) and 15 years (29 years) under warming levels of 1.5, 2.0, 3.0 and 4.0°C, respectively. Northwestern China (NW), southwestern China (SW) and the Yangtze River valley (YZ) exhibit the greatest increase in probability ratio (PR) under future climate condition. The risk of extreme precipitation events, currently expected to occur once every 50 years, will be nearly 11 (21) times more likely to occur under a climate warming by 3.0°C (4.0°C). Limiting warming to 1.5°C will help avoid approximately 40%-50%, 70%-80% and over 90% of the increase in the risk of extreme events in almost all subregions if the global mean surface temperature (GMST) continues warming to 2.0°C, 3.0°C and 4.0°C, respectively. Our study provides a useful information for the understanding the impact of climate change on the future risk of extreme events over China.

Analyzing China's coal-related carbon emissions from economic growth perspective: Through decoupling and decomposition model.

To evaluate the relationship between coal-related carbon emissions (CCE) and economic growth, this paper analyzed the decoupling relationship between CCE and economic growth from national and provincial perspectives during period 1997-2016 through Tapio Decoupling Index. Then, to recognize its spatial characteristics during 1997-2016, gravity model was adopted to study the geographical changes of CCE. Finally, to identify the changes of (CCE) in China and reveal its internal driving forces, this paper employs the logarithmic mean Divisia index (LMDI) decomposition analysis to decompose decoupling indicator into six effects including emission factors, energy intensity, fossil energy structure, energy consumption structure, activity, and population at national and provincial levels. The results reflect that (1) CCE of China rose by 168.37% from 1997 to 2016, and reached the peak of 7948.43 Mton in 2013. The center of gravity has shifted from (114.64 E, 34.70 N) to (113.48 E, 35.06 N). (2) The decoupling curve showed an inverted "U" shape. The economic growth of 18 provinces has achieved a strong decoupling from CCE by 2016. Only Xinjiang, Shanxi, and Shaanxi's economic growth has increased the dependence on CCE. (3) Activity and energy intensity effects were the dominant factors driving and curbing the increase of decoupling indicator respectively.

Particulate-Based Single-Dose Local Immunosuppressive Regimen for Inducing Tolerogenic Dendritic Cells in Xenogeneic Islet Transplantation.

Recent studies emphasize on developing immune tolerance by an interim administration of various immunosuppressive drugs. In this study, a robust protocol is reported for local immunomodulation using a single-dose of FK506 microspheres and clodronate liposomes (mFK+CLO) in a xenogeneic model of islet transplantation. Surprisingly, the single-dose treatment with mFK+CLO induce tolerance to the islet xenograft. The recipient mice display tolerogenic dendritic cells (tDCs) with decreased antigen presenting ability and T cell activation capacity. Furthermore, a reduced percentage of CD4+ and CD8+ T cells and an impaired differentiation of naïve CD4+ T cells into interferon-γ producing Th1 and interleukin-17 producing Th17 cells are observed. In addition, the immunosuppressive protocol leads to the generation of Foxp3+ regulatory T cells (Tregs) which are required for the long-term graft survival. The enhanced generation of tDCs and Tregs by the single treatment of mFK+CLO cause xenograft tolerance, suggesting a possible clinical strategy which may pave the way towards improving therapeutic outcomes of clinical islet transplantation.

A common signaling pathway leading to degranulation in mast cells and its regulation by CCR1-ligand.

BACKGROUND: Signal transduction pathways mediated by various receptors expressed on mast cells are thought to be complex, and inhibitory signals that turn off activating signals are not known. METHODS: Upstream signaling cascades mediated by several known receptors in bone marrow-derived mast cells that lead to degranulation and mediator release were studied by immunoblotting and immunoprecipitation. Small interfering RNAs and knockout mice were used to confirm findings. RESULTS: All ligands tested including IgE/Ag, SCF, HSP70, CCL3, and its valiant eMIP induced phosphorylation of linker for activation of T cells (LAT), which triggered their receptor-mediated downstream signaling cascades that controlled degranulation and mediator release. Phosphorylation of lymphocyte-specific protein kinase (Lck) was induced by each ligand, which commonly played an indispensable role in LAT phosphorylation. In contrast, phosphorylation of spleen tyrosine kinase was additionally induced in cells stimulated only with IgE/Ag and SCF, which is also associated with LAT phosphorylation in part. Degranulation and mediator release induced by IgE/Ag, SCF, or HSP70 were enhanced by nanomolar doses of CCR1 ligands CCL3 and eMIP via enhanced LAT phosphorylation. On the other hand, micromolar doses of CCR1 ligand inhibited degranulation and mediator release from mast cells stimulated with IgE/Ag, SCF, or HSP70 by de-phosphorylation of phosphorylated Lck with Src homology region 2 domain-containing phosphatase-1. CONCLUSIONS: Linker for activation of T cells plays a central role in signal transduction pathways in mast cells stimulated with any ligand tested. Dose-dependent alternate costimulation and inhibition of CCR1 ligands in IgE/Ag-, SCF-, or HSP70-stimulated mast cells occur at the level of Lck-LAT phosphorylation.

Engineering "cell-particle hybrids" of pancreatic islets and bioadhesive FK506-loaded polymeric microspheres for local immunomodulation in xenogeneic islet transplantation.

Host immune response remains an obstacle in cell-replacement therapy for treating type I diabetes. Long-term systemic immunosuppression results in suboptimal efficacy and adverse reactions. Thus, "cell-particle hybrids" of pancreatic islets and tissue-adhesive, polydopamine-coated, FK506-loaded biodegradable microspheres (PD-FK506-MS) were developed to locally modulate the immune response at the transplantation site. Coating of FK506-MS with PD enabled the rapid formation of stable cell-particle hybrids without significant changes in islet viability and functionality. Extremely low quantities of FK506 (approximately 600 ng per recipient) sustainably released from cell-particle hybrids effectively prolonged survival of xenogeneic islet graft. Interestingly, FK506 exhibited extended bioavailability in the grafts but was undetectable in systemic circulation and other tissues. Moreover, mRNA expression of inflammatory cytokines was significantly inhibited in the PD-FK506-MS-containing grafts but not in lymphoid organs. This study presents a promising platform that facilitates the translation of local immunomodulation towards an effective strategy with improved safety profiles for treating type I diabetes.

Activation of Mevalonate Pathway via LKB1 Is Essential for Stability of Treg Cells.

The function of regulatory T (Treg) cells depends on lipid oxidation. However, the molecular mechanism by which Treg cells maintain lipid metabolism after activation remains elusive. Liver kinase B1 (LKB1) acts as a coordinator by linking cellular metabolism to substrate AMP-activated protein kinase (AMPK). We show that deletion of LKB1 in Treg cells exhibited reduced suppressive activity and developed fatal autoimmune inflammation. Mechanistically, LKB1 induced activation of the mevalonate pathway by upregulating mevalonate genes, which was essential for Treg cell functional competency and stability by inducing Treg cell proliferation and suppressing interferon-gamma and interleukin-17A expression independently of AMPK. Furthermore, LKB1 was found to regulate intracellular cholesterol homeostasis and to promote the mevalonate pathway. In agreement, mevalonate and its metabolite geranylgeranyl pyrophosphate inhibited conversion of Treg cells and enhanced survival of LKB1-deficient Treg mice. Thus, LKB1 is a key regulator of lipid metabolism in Treg cells, involved in optimal programming of suppressive activity, immune homeostasis, and tolerance.

BJ-2266 ameliorates experimental autoimmune encephalomyelitis through down-regulation of the JAK/STAT signaling pathway.

CD4+ T cells differentiate into distinct effector subsets upon antigenic stimulation. Cytokines, and micro-environmental factors present during T-cell priming, direct differentiation of naïve CD4+ T cells into pro-inflammatory Th1 and Th17 cells. From extensive screening of 2,4,5-trimethylpyridin-3-ol derivatives with various functional groups at C(6)-position, BJ-2266, a 6-thioureido-derivative, showed potent inhibitory activity on in vitro T helper (Th)-cell differentiation. This compound inhibited IFN-γ and IL-17 production from polyclonal CD4+ T cells and ovalbumin (OVA)-specific CD4+ T cells that were activated by T-cell receptor (TCR) engagement. We assessed the inhibitory effect of BJ-2266 in experimental autoimmune encephalomyelitis (EAE). Our results suggest that BJ-2266 treatment significantly suppresses EAE disease progression with reduced generation of Th1 and Th17 cells. Notably, Th-cell differentiation was significantly suppressed by BJ-2266 treatment with no effect on apoptosis, activation and proliferation of activated T cells. Furthermore, adoptive transfer of BJ-2266 treated MOG-reactive Th1 and Th17 cells led to a lower EAE disease score and better clinical recovery from EAE. The underlying mechanism of BJ-2266 effect involved the inhibition of JAK/STAT phosphorylation that is critical for Th-cell differentiation. We conclude that BJ-2266 regulates the JAK/STAT pathway in response to cytokine signals and subsequently suppresses the differentiation of Th-cell responses.

BJ-3105, a 6-Alkoxypyridin-3-ol Analog, Impairs T Cell Differentiation and Prevents Experimental Autoimmune Encephalomyelitis Disease Progression.

CD4+ T cells are essential in inflammation and autoimmune diseases. Interferon-γ (IFN-γ) secreting T helper (Th1) and IL-17 secreting T helper (Th17) cells are critical for several autoimmune diseases. To assess the inhibitory effect of a given compound on autoimmune disease, we screened many compounds with an in vitro Th differentiation assay. BJ-3105, a 6-alkoxypyridin-3-ol analog, inhibited IFN-γ and IL-17 production from polyclonal CD4+ T cells and ovalbumin (OVA)-specific CD4+ T cells which were activated by T cell receptor (TCR) engagement. BJ-3105 ameliorated the experimental autoimmune encephalomyelitis (EAE) model by reducing Th1 and Th17 generation. Notably, Th cell differentiation was significantly suppressed by BJ-3105 treatment without inhibiting in vitro proliferation of T cells or inducing programmed cell death. Mechanistically, BJ-3105 inhibited the phosphorylation of JAK and its downstream signal transducer and activator of transcription (STAT) that is critical for Th differentiation. These results demonstrated that BJ-3105 inhibits the phosphorylation of STAT in response to cytokine signals and subsequently suppressed the differentiation of Th cell responses.