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Background: Chronic stress-induced neuroinflammation plays a pivotal role in the development and exacerbation of mental disorders, such as anxiety and depression. Dimethyl Fumarate (DMF), an effective therapeutic agent approved for the treatment of multiple sclerosis, has been widely reported to display anti-inflammatory and anti-oxidative effects. However, the impact of DMF on chronic stress-induced anxiety disorders and the exact underlying mechanisms remain largely unknown., Methods: We established a mouse model of chronic social defeat stress (CSDS). DMF was administered orally 1 h before daily stress session for 10 days in CSDS + DMF group. qRT-PCR and western blotting were used to analyze mRNA and protein expression of NLRP3, Caspase-1 and IL-1β. Immunofluorescence staining was carried out to detect the expression of Iba 1 and c-fos positive cells as well as morphological change of Iba 1 + microglia. Whole-cell patch-clamp recording was applied to evaluate synaptic transmission and intrinsic excitability of neurons., Results: DMF treatment significantly alleviated CSDS-induced anxiety-like behaviors in mice. Mechanistically, DMF treatment prevented CSDS-induced neuroinflammation by inhibiting the activation of microglia and NLRP3/Caspase-1/IL-1β signaling pathway in basolateral amygdala (BLA), a brain region important for emotional processing. Furthermore, DMF treatment effectively reversed the CSDS-caused disruption of excitatory and inhibitory synaptic transmission balance, as well as the increased intrinsic excitability of BLA neurons., Conclusions: Our findings provide new evidence that DMF may exert anxiolytic effect by preventing CSDS-induced activation of NLRP3/Caspase-1/IL-1β signaling pathway and alleviating hyperactivity of BLA neurons., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Climate change presents formidable challenges to forest biodiversity and carbon storage. Bamboo forests will be affected particularly in Southwest China's mountainous regions. Bamboo serves as not only a key food resource and habitat for giant panda Ailuropoda melanoleuca but also a potential carbon sink due to its rapid energy-to-matter conversion capability. We employ the MaxEnt model to project the distribution shifts of 20 giant panda foraged bamboo species in Sichuan Province under future climate scenarios, utilizing climate data of 30m resolution. Based on the changes in the diversity and distribution area of bamboo communities caused by climate change, the changing of giant pandas' food resources and the carbon storage of bamboo forests were calculated. The results indicated that the area of bamboo communities is projected to expand by 17.94%-60.88% more than now by the end of the 21st century. We analyzed the energy balance between the dietary needs of giant pandas and the energy provided by bamboo. We predicted that bamboo communities from 2000 to 2150 could support the continuous growth of the giant panda population (6533 wild individuals by 2140-2150 in an ideal state in Sichuan province). However, the species diversity and carbon storage of bamboo forests face out-of-sync fluctuations, both temporally and spatially. This is a critical issue for subalpine forest ecosystem management under climate change. Therefore, we propose a dynamic conservation management framework for giant panda habitats across spatial and temporal scales. This framework aims to facilitate the adaptation of subalpine forest ecosystems to climate change. This innovative approach, which integrates climate change into the conservation strategy for endangered species, contributes a conservation perspective to global climate action, highlighting the interconnectedness of biodiversity preservation and climate mitigation., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, author-ship, and/or publication of this article., (Copyright © 2024. Published by Elsevier Ltd.)

Protected areas (PAs) are pivotal to biodiversity conservation, yet their efficacy is compromised by insufficient funding and management. So-called other effective area-based conservation measures (OECMs) present a paradigm shift and address PA limitations. Such measures can expand conservation areas, enhance connectivity, and improve the existing system. To assess the conservation status of biodiversity in Tibetan cultural areas in China, we investigated the spatial distribution of wildlife vulnerable to human disturbance (large- and medium-sized mammals and terrestrial birds) in Xinlong, a traditional Tibetan cultural area. In particular, we compared a PA (Xionglongxi Nature Reserve) and OECMs targeting species conservation. We also investigated the relationship of wildlife with human temporal and spatial activities. The OECMs complemented areas not covered by PA, especially in rich understory biodiversity regions. More species in OECMs tolerated human presence than species in the PA. Existing biodiversity reserves failed to cover areas of high conservation value in Tibet and offered limited protection capacity. Expanding PAs and identifying OECMs improved Xinlong's system by covering most biodiversity hotspots. Building on the tradition of wildlife conservation in Tibet, harnessing OECMs may be an effective means of augmenting biodiversity conservation capacity. We recommend further evaluation of OECMs effectiveness and coverage in Tibetan area as a way to enhance the current PA system., (© 2024 The Authors. Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

This study enhances the ultrafast photonics application of tin selenide (SnSe) nanoflakes via copper (Cu) functionalization to overcome challenges such as low conductivity and weak near-infrared (NIR) absorption. Cu functionalization enhances concentration, induces strain, and reduces the bandgap through Sn substitution and Sn vacancy filling with Cu ions. Demonstrated by density functional theory calculations and experimental analyses, Cu-functionalized SnSe exhibits improved NIR optical absorption and superior third-order nonlinear optical properties. Z-scan measurements and femtosecond transient absorption spectroscopy reveal better performance of Cu-functionalized SnSe in terms of nonlinear optical properties and shorter carrier relaxation times compared to pristine SnSe. Furthermore, saturable absorbers based on both SnSe types, when integrated into an erbium-doped fiber laser, show that Cu functionalization leads to a decrease in pulse duration to 798 fs and an increase in 3 dB spectral bandwidth to 3.44 nm. Additionally, it enables stable harmonic mode-locking of bound-state solitons. This work suggests a new direction for improving wide bandgap 2D materials by highlighting the enhanced nonlinear optical properties and potential of Cu-functionalized SnSe in ultrafast photonics., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Low-dimensional lead halide perovskites demonstrate remarkable nonlinear optical characteristics attributed to their distinctive physical structures and electronic properties. Nevertheless, the investigation into their nonlinear optical properties remains in its incipient stages. This study addresses this gap by precisely controlling solvent volumes to synthesize both 0D Cs 4 PbBr 6 and Cs 4 PbBr 6 /CsPbBr 3 perovskites. Remarkably, as saturable absorbers, both pure Cs 4 PbBr 6 and Cs 4 PbBr 6 /CsPbBr 3 composites exhibit favorable nonlinear optical properties within the C-band, showcasing modulation depths of 9.22% and 16.83%, respectively. Moreover, for the first time, Cs 4 PbBr 6 and Cs 4 PbBr 6 /CsPbBr 3 composites have been successfully integrated into erbium-doped fiber lasers to realize the mode-locking operations. The utilization of the Cs 4 PbBr 6 /CsPbBr 3 composites as a saturable absorber that enables the generation of conventional soliton mode-locked laser pulses with a pulse duration of 688 fs, and a repetition frequency of 10.947 MHz at a central wavelength of 1557 nm. Cs 4 PbBr 6 is instrumental in generating laser pulses at a frequency of 10.899 MHz, producing pulse widths of 642 fs at the central wavelength of 1531.2 nm and 1.02 ps at the central wavelength of 1565.3 nm, respectively. The findings of this investigation underscore the potential utility of 0D Cs 4 PbBr 6 and Cs 4 PbBr 6 /CsPbBr 3 composites as promising materials for optical modulation within fiber laser applications., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Thrombosis, characterized by blood clot formation within vessels, poses a significant medical challenge. Despite extensive research, the development of effective thrombosis therapies is hindered by substantial costs, lengthy development times, and high failure rates in medication commercialization. Conventional pre-clinical models often oversimplify cardiovascular disease, leading to a disparity between experimental results and human physiological responses. In response, we have engineered a photothrombosis-on-a-chip system. This microfluidic model integrates human endothelium, human whole blood, and blood flow dynamics and employs the photothrombotic method. It enables precise, site-specific thrombus induction through controlled laser irradiation, effectively mimicking both normal and thrombotic physiological conditions on a single chip. Additionally, the system allows for the fine-tuning of thrombus occlusion levels via laser parameter adjustments, offering a flexible thrombus model with varying degrees of obstruction. Additionally, the formation and progression of thrombosis noted on the chip closely resemble the thrombotic conditions observed in mice in previous studies. In the experiments, we perfused recalcified whole blood with Rose Bengal into an endothelialized microchannel and initiated photothrombosis using green laser irradiation. Various imaging methods verified the model's ability to precisely control thrombus formation and occlusion levels. The effectiveness of clinical drugs, including heparin and rt-PA, was assessed, confirming the chip's potential in drug screening applications. In summary, the photothrombosis-on-a-chip system significantly advances human thrombosis modeling. Its precise control over thrombus formation, flexibility in the thrombus severity levels, and capability to simulate dual physiological states on a single platform make it an invaluable tool for targeted drug testing, furthering the development of organ-on-a-chip drug screening techniques.

We report on the Czochralski crystal growth, polarized optical spectroscopy, and the first continuous-wave laser operation of 1.5 at.% Tm:LuVO 4 crystal on the 3 H 4 → 3 H 5 transition. The polarized absorption and stimulated-emission properties of Tm 3+ ions in LuVO 4 were revised and the crystal-field splitting of the Tm 3+ multiplets was determined by low-temperature (12 K) spectroscopy. The maximum stimulated-emission cross-section for the 3 H 4 → 3 H 5 transition is 2.48 × 10 -20 cm 2 at 2363 nm for π-polarization corresponding to an emission bandwidth of 28 nm. Evidence of phonon-assisted emissions of Tm 3+ ions above 2 µm is presented. The broadband emission properties of the Tm:LuVO 4 crystal make it promising for ultrashort pulse generation. Additionally, pumped by a 796 nm fiber-coupled laser diode, the Tm:LuVO 4 laser generated a Watt-level output power at 2279-2295 nm with a slope efficiency of 9.2% and linearly polarized emission (π-polarization).

The polarized spectral properties and ∼2.3 µm high-power continuous-wave laser operation of Tm 3+ -doped yttrium orthovanadate crystal (Tm:YVO 4 ) are reported. For the 3 H 4 → 3 H 5 transition, the stimulated-emission cross-section σ SE is 1.01 × 10 -20 cm 2 at 2276 nm corresponding to a large emission bandwidth of 52 nm (for π-polarization). Pumped by a 794 nm laser diode, the 1.5 at.% Tm:YVO 4 laser delivered 5.52 W at 2.29 µm with a slope efficiency of 19.9%, a laser threshold of 8.70 W, and a linear laser polarization (π). The Tm laser operated on the cascade scheme (on the 3 H 4 → 3 H 5 and 3 F 4 → 3 H 6 transitions) which was mainly responsible for the observed high laser slope efficiency. We also report on the first passively Q-switched Tm:YVO 4 laser at 2.3 µm by employing porous nano-grained cuprous selenide (PNG-Cu 2 Se) as a saturable absorber. The shortest pulse duration and the highest single pulse energy amounted to 706 ns and 3.65 µJ, respectively, corresponding to a pulse repetition rate of 62.8 kHz.

After the first report of a graphene-based passive mode-locking ultrafast fiber laser, two-dimensional materials as efficient saturable absorbers offer a new horizon in ultrafast fiber laser. However, the interactions on atomic scale between these two-dimensional materials and fiber and the fiber effect on the carrier dynamics have not been realized. To figure out the exact role of fiber and the carrier dynamics affected by the fiber substrate related to ultrafast photonics, bismuthene, a newly reported 2D quantum material used in a passive mode-locking fiber laser, deposited on α-quartz has been investigated. We surprisingly found that the α-quartz substrate can strongly accelerate the nonradiative electron-hole recombination of bismuthene in theory, and the transient absorption spectra of bismuthene on normal glass and α-quartz further verify the substrate effect on carrier dynamics of bismuthene. The discovery provides new thinking about substrate effect to regulate the performance of ultrafast mode-locking fiber lasers as well as ultrafast photonics.

As a new member of two-dimensional (2D) phosphorene, 2D layered violet phosphorus (VP) has unique optoelectronic properties and good environmental stability, showing its huge advantages in optoelectronic applications. In this paper, the ultrafast nonlinear optical (NLO) properties of layered VP nanosheets at 1 µm band were explored, which exhibit an obvious saturable absorption response with a modulation depth of ∼1.97%. Meanwhile, the fast and slow carrier lifetimes of VP nanosheets at 1µm band were also determined as 295.9 fs and 2.36 ps, respectively, which are much shorter than that of most reported 2D materials. The excellent saturable absorption response combined with ultrashort carrier lifetimes indicate the prospect of layered VP nanosheets as a fast saturable absorber (SA) for ultrafast laser modulation. Then we demonstrated a Yb-doped fiber laser based on the VP-deposited taper-shaped fiber (TSF) SA, which delivers stable Q-switched mode-locked (QSML) pulses, dual-wavelength mode-locked pulses and 404-fs noise-like pulses. This work fully demonstrates the great potential of 2D VP materials for 1 µm ultrashort laser pulse generation.

Arterial stiffness has been proved to be an important parameter in the evaluation of cardiovascular diseases, and Pulse Wave Velocity (PWV) is a strong indicator of arterial stiffness. Compared to regional PWV (PWV among different arteries), local PWV (PWV within a single artery) outstands in providing higher precision in indicating arterial properties, as regional PWVs are highly affected by multiple parameters, e.g., variations in blood vessel lengths due to individual differences, and multiple reflection effects on the pulse waveform. However, local PWV is less-developed due to its high dependency on the temporal resolution in synchronized signals with usually low signal-to-noise ratios. This paper presents a method for the noninvasive simultaneous measurement of two local PWVs in both left and right radial arteries based on the Fiber Bragg Grating (FBG) technique via correlation analysis of the pulse pairs at the fossa cubitalis and at the wrist. Based on the measurements of five male volunteers at the ages of 19 to 21 years old, the average left radial PWV ranged from 9.44 m/s to 12.35 m/s and the average right radial PWV ranged from 11.50 m/s to 14.83 m/s. What is worth mentioning is that a stable difference between the left and right radial PWVs was observed for each volunteer, ranging from 2.27 m/s to 3.04 m/s. This method enables the dynamic analysis of local PWVs and analysis of their features among different arteries, which will benefit the diagnosis of early-stage arterial stiffening and may bring more insights into the diagnosis of cardiovascular diseases.

Inactivity can lead to muscle atrophy and capillary regression in skeletal muscle. Niacin (NA), known for inducing hypermetabolism, may help prevent this capillary regression. In this study involving adult female Sprague-Dawley rats, the animals were randomly assigned to one of four groups: control (CON), hindlimb unloading (HU), NA, and HU with NA supplementation (HU + NA). For a period of 2 weeks, the rats in the HU and HU + NA groups underwent HU, while those in the NA and HU + NA groups received NA (750 mg/kg) twice daily through oral administration. The results demonstrated that HU lowered capillary number, luminal diameter, and capillary volume, as well as decreased succinate dehydrogenase activity, slow fiber composition, and PGC-1α expression within the soleus muscle. However, NA supplementation prevented these alterations in capillary structure due to unloading by stimulating PGC-1α factors and inhibiting mitochondrial dysfunction. Therefore, NA supplementation could serve as a potential therapeutic approach for preserving the capillary network and mitochondrial metabolism of muscle fibers during periods of inactivity., (© 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Herein, a Sc(OTf) 3 -catalyzed (3+2) annulation of 2-indolylmethanols with propargylic alcohols is reported. The reaction proceeds via a Friedel-Crafts-type allenylation/5-exo-annulation cascade. In the reaction, 2-indolylmethanol is used as a three-carbon synthon, and propargyl alcohol is used as a two-carbon synthon. This method provides a direct and high-yield pathway for synthetically useful cyclopenta[ b ]indoles. In general, the method features easily accessible substrates with broad scope and generality, the formation of multiple bonds with high efficiency, and easy scale-up.

The baijiu fermentation environment hosts a variety of micro-organisms, some of which still remain uncultured and uncharacterized. In this study, the isolation, cultivation and characterization of three novel aerobic bacterial strains are described. The cells of strain REN20 T were Gram-negative, strictly aerobic, motile and grew at 26-37 °C, at pH 6.0-9.0 and in the presence of 0-5.0   % (w/v) NaCl. The cells of strain REN29 T were Gram-negative, strictly aerobic, motile and grew at 15-30 °C, at pH 6.0-9.0 and in the presence of 0-10.0   % (w/v) NaCl. The cells of strain REN33 T were Gram-positive, strictly aerobic, motile and grew at 15-37 °C, at pH 5.0-10.0 and in the presence of 0-7.0   % (w/v) NaCl. The digital DNA-DNA hybridization and average nucleotide identity by orthology values between type strains in related genera and REN20 T (20.3-36.8 % and 79.8-89.9  %), REN29 T (20.3-36.8  % and 74.5-88.5  %) and REN33 T (22.6-48.6  % and 75.8-84.2  %) were below the standard cut-off criteria for the delineation of bacterial species, respectively. Based on polyphasic taxonomy analysis, we propose three new species, Bosea beijingensis sp. nov. (=REN20 T =GDMCC 1.2894 T =JCM 35118 T ), Telluria beijingensis sp. nov. (=REN29 T =GDMCC 1.2896 T =JCM 35119 T ) and Agrococcus beijingensis sp. nov. (=REN33 T =GDMCC 1.2898 T =JCM 35164 T ), which were recovered during cultivation and isolation from baijiu mash.

The laser diode (LD)-pumped Tm:YAP (a-cut, 3.5 at.%) laser generated a maximum ∼2.3 µm continuous wave (CW) laser output power of ∼3 W. The higher output power benefited from the positive effect of the cascade lasing (simultaneously operating on the 3 H 4 → 3 H 5 and 3 F 4 → 3 H 6 Tm 3+ transition). It was the highest CW laser output power amongst the LD/Ti:Sapphire-CW-pumped ∼2.3 µm Tm 3+ -doped lasers reported so far. Under the cascade laser operation, the slope efficiency of the ∼2.3 µm laser emission versus the absorbed pump power increased from 13.0% to 21.4%.

A compact Tm:GdVO 4 laser pumped by a 794 nm laser diode generated 6.09 W at 2.29 µm ( 3 H 4  →  3 H 5 Tm 3+ transition) with a high slope efficiency of 30.8% and linear laser polarization (π). The polarized spectroscopic properties of Tm 3+ in GdVO 4 were also revised. The peak stimulated-emission cross section of Tm 3+ is 2.97 × 10 -20 cm 2 at 2280 nm, corresponding to an emission bandwidth of 42 nm for π-polarized light.

The habitat plays a crucial role in ensuring the survival of wildlife. However, the increasing disturbances caused by human activities present a substantial threat to habitats, especially for species such as the leopard cat ( Prionailurus bengalensis ), which is a significant small predator. Currently, research on leopard cats predominantly focuses on low-altitude regions within its distribution range, leaving plateau areas understudied. To enhance our understanding of the impact of human disturbances on leopard cat habitats, we undertook a study employing infrared camera trappings to monitor leopard cats' activity in Xinlong of southwestern China between 2015 and 2023. We analyzed the spatial distribution and habitat suitability of the leopard cats by utilizing ensemble species distribution models (ESDMs). Moreover, we employed two-species occupancy models to investigate the spatial interaction between leopard cats and human disturbances. The results indicated that (1) the potential suitable habitat area for leopard cats encompassed approximately 1324.93 km 2 (14.3%), primarily located along the banks of Yalong river. (2) The distribution of suitable habitat was predominantly influenced by competitors, specifically the yellow-throated marten (YTM), accounting for 52.4% of the influence, as well as environmental factors such as distance to water (DTW) at 12.0% and terrain roughness index (TRI) at 10.0%. Human interference, including cattle presence (4.6%), distance to road (DTD, 4.9%), and distance to settlement (DTS, 3.5%), had a limited impact on the habitat distribution. (3) Within a 5 km radius, habitat suitability increased with proximity to human settlements. (4) Leopard cats exhibited spatial independence from humans and domestic cattle (species interaction factor (SIF) = 1.00) while avoiding domestic horses (SIF = 0.76 ± 0.03). The relatively minor impact of human disturbances in Xinlong could be attributed to traditional cultural practices safeguarding wildlife and the leopard cat's environmental adaptability. We recommend establishing a novel conservation paradigm based on the living dynamics of wildlife communities in Xinlong, thereby offering a more targeted approach to biodiversity preservation in the future.

One of the most sought-after topics in neuroscience is to understand how the environment regulates the activity and function of neural circuitry and subsequently influences relevant behaviors. In response to alterations in the environment, the neural circuits undergo adaptive changes ranging from gene expression changes to altered cellular function. Performing sequencing of the transcriptome involved in these behavior-related circuits will provide clues to accurately dissect the detailed mechanisms of related behavior. Here, we describe methods for marking and collecting the ventral hippocampus-projecting basolateral amygdala neurons, which have been repeatedly implicated in regulation of anxiety-like behavior, and subsequently constructing a library ready for sequencing. Specifically, the reported approaches include adeno-associated virus injection, acute brain slice isolation, cell suspension preparation, cell extraction, and cDNA library construction. By utilizing the techniques described here, researchers can comprehensively investigate the transcriptional levels of neural clusters embedded in particular circuits and discover potential pathogenic and therapeutic targets for behavior-relevant disorders. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Tagging of behavior-related neural circuits Basic Protocol 2: Isolation and capture of fluorescent-positive cells Basic Protocol 3: Foundation of sequencing library., (© 2023 Wiley Periodicals LLC.)

The laser diode (LD)-pumped efficient high-power cascade Tm:GdVO 4 laser simultaneously operating on the 3 F 4 → 3 H 6 (at ∼2 μm) and 3 H 4 → 3 H 5 (at ∼2.3 μm) Tm 3+ transition was first reported in this paper. The cascade Tm:GdVO 4 laser generated a maximum total continuous-wave (CW) laser output power of 8.42 W with a slope efficiency of 40%, out of which the maximum ∼2.3 μm CW laser output power was 2.88 W with a slope efficiency of 14%. To our knowledge, 2.88 W is the highest CW laser output power amongst the LD-CW-pumped ∼2.3 μm Tm 3+ -doped lasers reported so far.

Chiral ketones and their derivatives are useful synthetic intermediates for the synthesis of biologically active natural products and medicinally relevant molecules. Nevertheless, general and broadly applicable methods for enantioenriched acyclic α,α-disubstituted ketones, especially α,α-diarylketones, remain largely underdeveloped, owing to the easy racemization. Here, we report a visible light photoactivation and phosphoric acid-catalyzed alkyne-carbonyl metathesis/transfer hydrogenation one-pot reaction using arylalkyne, benzoquinone, and Hantzsch ester for the expeditious synthesis of α,α-diarylketones with excellent yields and enantioselectivities. In the reaction, three chemical bonds, including C═O, C─C, and C─H, are formed, providing a de novo synthesis reaction for chiral α,α-diarylketones. Moreover, this protocol provides a convenient and practical method to synthesize or modify complex bioactive molecules, including efficient routes to florylpicoxamid and BRL-15572 analogs. Computational mechanistic studies revealed that C-H/π interactions, π-π interaction, and the substituents of Hantzsch ester all play crucial roles in the stereocontrol of the reaction.

The exceptional mechanical, electronic, topological, and optical properties, make bismuthene an ideal candidate for various applications in ultrafast saturation absorption and spintronics. Despite the extensive research efforts devoted to synthesizing this material, the introduction of defects, which can significantly affect its properties, remains a substantial obstacle. In this study, we investigate the transition dipole moment and joint density of states of bismuthene with/without single vacancy defect via energy band theory and interband transition theory. It is demonstrated that the existence of the single defect enhances the dipole transition and joint density of states at lower photon energies, ultimately resulting in an additional absorption peak in the absorption spectrum. Our results suggest that the manipulation of defects in bismuthene has enormous potential for improving the optoelectronic properties of this material.

Background: Chronic stress exposure increases the risk of mental health problems such as anxiety and depression. The medial prefrontal cortex (mPFC) is a hub for controlling stress responses through communicating with multiple limbic structures, including the basolateral amygdala (BLA) and nucleus accumbens (NAc). However, considering the complex topographical organization of the mPFC neurons in different subregions (dmPFC vs. vmPFC) and across multiple layers (Layer II/III vs. Layer V), the exact effects of chronic stress on these distinct mPFC output neurons remain largely unknown., Results: We first characterized the topographical organization of mPFC neurons projecting to BLA and NAc. Then, by using a typical mouse model of chronic restraint stress (CRS), we investigated the effects of chronic stress on the synaptic activity and intrinsic properties of the two mPFC neuronal populations. Our results showed that there was limited collateralization of the BLA- and NAc-projecting pyramidal neurons, regardless of the subregion or layer they were situated in. CRS significantly reduced the inhibitory synaptic transmission onto the BLA-projecting neurons in dmPFC layer V without any effect on the excitatory synaptic transmission, thus leading to a shift of the excitation-inhibition (E-I) balance toward excitation. However, CRS did not affect the E-I balance in NAc-projecting neurons in any subregions or layers of mPFC. Moreover, CRS also preferentially increased the intrinsic excitability of the BLA-projecting neurons in dmPFC layer V. By contrast, it even caused a decreasing tendency in the excitability of NAc-projecting neurons in vmPFC layer II/III., Conclusion: Our findings indicate that chronic stress exposure preferentially modulates the activity of the mPFC-BLA circuit in a subregion (dmPFC) and laminar (layer V) -dependent manner., (© 2023. The Author(s).)

An innovated model-free interaction screening procedure called the MCVIS is proposed for high dimensional data analysis. Specifically, we adopt the introduced MCV index for quantifying the importance of an interaction effect among predictors. Our proposed method is fully nonparametric and is capable of successfully selecting interactions even if the signal of parental main effects is weak. The MCVIS procedure has many distinctive features: (i) it can work with discrete, categorical and continuous covariates; (ii) it can deal with both categorical and continuous response, even handle the missing response; (iii) it is robust for heavy-tailed distributions, thus well accommodates heterogeneity typically caused by high dimensionality; (iv) it enjoys the sure screening and ranking consistency properties, therefore achieves dimension reduction without information loss. In another respect, computational feasibility is a top concern in high dimensional data analysis, by transforming our MCV into several variants, the MCVIS procedure is simple and fast to implement. Extensive numerical experiments and comparisons confirm the effectiveness and wide applicability of our MCVIS procedure. We further illustrate the proposed methodology by empirical study of two real datasets. Supplementary materials are available online., (© 2023 John Wiley & Sons Ltd.)

We report on the cascade continuous-wave operation of a diode-pumped Tm:YVO 4 laser on the 3 F 4 → 3 H 6 (at ∼2 μm) and 3 H 4 → 3 H 5 (at ∼2.3 μm) Tm 3+ transitions. Pumped with a fiber-coupled spatially multimode 794 nm AlGaAs laser diode, the 1.5 at.% Tm:YVO 4 laser yielded a maximum total output power of 6.09 W with a slope efficiency of 35.7% out of which the 3 H 4 → 3 H 5 laser emission corresponded to 1.15 W at 2291-2295 and 2362-2371 nm with a slope efficiency of 7.9% and a laser threshold of 6.25 W.

Background: Glucose 6 phosphatase dehydrogenase (G6PD) is a key regulator of the pentose phosphate pathway (PPP). However, the exact role of G6PD in gastrointestinal cancers remains unclear. The purpose of this study is to explore the correlation of G6PD with clinical features, pathological stages, diagnosis and prognosis of gastrointestinal cancers, as well as uncover possible mechanisms of G6PD on mutations, immunity and signaling pathways., Methods: G6PD mRNA expression data were downloaded from TCGA and GEO databases. Protein expression was examined by the HPA database. The correlation of G6PD expression with clinical and pathological characteristics was explored. The pROC package in R language was used to evaluate the diagnostic value of G6PD expression in gastrointestinal cancers. We accessed the correlation of disease-free survival (DFS) with G6PD online by Kaplan-Meier plotter. Univariate Cox regression and stepwise multiple Cox regression analysis were performed to determine the association between G6PD and patient's overall survival. In addition, genomic alterations, mutation profiles, immune infiltration, drug sensitivity and enrichment analysis related with G6PD were visualized., Results: After a pan-cancerous genomic analysis, we found that G6PD expression was the highest in African American esophageal carcinoma (ESCA) patients ( P <0.05). G6PD was correlated with age, weight, disease stage, lymph node metastasis and pathological grade. Notably, G6PD showed an excellent predictive diagnosis ability for liver hepatocellular carcinoma (LIHC) (AUC=0.949, 95% CI=0.925-0.973, P <0.001). G6PD can improve the DFS of esophageal adenocarcinoma (EAC) and pancreatic adenocarcinoma (PAAD) patients ( P <0.05). Both Univariate Cox regression and stepwise multiple Cox regression analysis in R language determined that G6PD expression was closely related with LIHC ( P <0.001). G6PD was found to have a high mutation rate in colon adenocarcinoma and ESCA and gene amplification in ESCA, Cholangiocarcinoma, PAAD and LIHC. Copy number of G6PD was missing in LIHC. G6PD was also related to mutation of TP53 ( P <0.05). Particularly, it was positively correlated with CD276 in all gastrointestinal cancers and negatively with HERV-H LTR-associating 2 in ESCA and stomach adenocarcinoma. The abnormal expression of G6PD was related to the increase of CD4+ Th2 subsets and the decrease of CD4+ (non-regulatory) of T cells. G6PD was sensitive to FK866, Phenformin, AICAR etc., while resistant to RO-3306, CGP-082996, TGX221 etc. G6PD was found to closely interact with TALDO1, GAPDH and TP53. G6PD related biological processes included aging, nutritional response and daunorubicin metabolism, and related pathways included PPP, cytochrome P450 metabolism of exogenous substances and glutathione metabolism., Conclusion: G6PD is highly expressed in gastrointestinal cancers. It is a carcinogenic indicator related to prognosis and can be used as a potential diagnostic marker of gastrointestinal cancers, so as to provide new strategy for cancer treatment., Competing Interests: None., (AJTR Copyright © 2023.)

Anxiety is a normal and transitory emotional state that allows the organisms to cope well with the real or perceived threats, while excessive or prolonged anxiety is a key characteristic of anxiety disorders. We have recently revealed that prolonged anxiety induced by chronic stress is associated with the circuit-varying dysfunction of basolateral amygdala projection neurons (BLA PNs). However, it is not yet known whether similar mechanisms also emerge for acute stress-induced, short-lasting increase of anxiety. Here, using a mouse model of acute restraint stress (ARS), we found that ARS mice showed increased anxiety-like behavior at 2 h but not 24 h after stress, and this effect was accompanied by a transient increase of the activity of BLA PNs. Specifically, ex vivo patch-clamp recordings revealed that the increased BLA neuronal activity did not differ among the distinct BLA neuronal populations, regardless of their projection targets being the dorsomedial prefrontal cortex (dmPFC) or elsewhere. We further demonstrated that such effects were mainly mediated by the enhanced presynaptic glutamate release in dmPFC-to-BLA synapses but not lateral amygdala-to-BLA ones. Furthermore, while optogenetically weakening the presynaptic glutamate release in dmPFC-to-BLA synapses ameliorated ARS-induced anxiety-like behavior, strengthening the release increased in unstressed mice. Together, these findings suggest that acute stress causes short-lasting increase in anxiety-like behavior by facilitating synaptic transmission from the prefrontal cortex to the amygdala in a circuit-independent fashion., (© 2022. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

The unique reactivity of in situ generated propargylic para- quinone methides as a new type of five-carbon synthon has been discovered by a novel bismuth(III)-catalyzed tandem annulation reaction. This 1,8-addition/cyclization/rearrangement cyclization cascade reaction is characterized by unusual structural reconstruction of 2-vinylphenol, involving cleavage of the C1'═C2' bond and formation of four new bonds. This method provides a convenient and mild approach to generate synthetically important functionalized indeno[2,1- c ]chromenes. The mechanism of the reaction is proposed from several control experiments.

The design and production of assembled buildings are difficult to standardise, which limits their extensive application. In this paper, the design for manufacture and assembly (DFMA) concept is applied to the design of vertical precast concrete (PC) components for assembled buildings. Taking vertical PC components as an example, the rapid modelling and whole life-cycle application of DFMA-oriented PC components for assembled buildings are investigated. Firstly, the modular design method is introduced. By combining parametric design and building information modelling (BIM), we propose a modular, parametric design method and process of PC components based on DFMA. Secondly, the design of standard modules after secondary splitting is introduced for a better DFMA-oriented parametric design of PC components. We explored the secondary development process of DFMA and BIM and the module creation process of the parametric standard based on family templates and DFMA. Thirdly, based on the parametric standard module, the application of the optimised whole life cycle of design, manufacture and assembly of PC components is introduced. Finally, the feasibility of this method is verified by practical cases. The design process for PC components is fast, accurate and standardised. The integrated application of BIM is accelerated, and digital collaboration in assembly construction is strengthened. The study results are conducive to establishing a standardised design and production system for PC components, reducing design costs, improving design efficiency and the comprehensive benefits of assembled buildings., (© 2023. The Author(s).)

In this contribution, we measured the third-order nonlinear optical response of bismuth oxychloride (BiOCl) nanosheets with the open-aperture (OA) and the closed-aperture (CA) Z-scan techniques with a variable excitation intensity at 1.34 µm. The effective nonlinear absorption coefficient βeff and the nonlinear refractive index n 2 of the prepared BiOCl nanosheets with abundant oxygen vacancies were obtained under the excitation intensity. The third-order nonlinear optical susceptibility |χ (3) | was 1.64 × 10 -9 esu. The nonlinear optical features of BiOCl enabled it as a superb saturable absorber for pulse laser generation. As a consequence, we demonstrated the first passively Q-switched Nd:GdVO 4 laser with the BiOCl saturable absorber, producing a shortest pulse duration of 543 ns and a highest repetition rate of 227 kHz, leading to a maximum pulse energy of 74 nJ. Our findings show that BiOCl nanosheets with oxygen vacancies have large nonlinear optical sensitivities and can be exploited to generate optical pulses.

Background: Huang Lian (HL), one of the traditional Chinese medicines (TCMs) that contains multiple active components including berberine (BBR), has been used to treat symptoms associated with diabetes for thousands of years. Compared to the monomer of BBR, HL exerts a better glucose-lowering activity and plays different roles in regulating gut microbiota. However, it remains unclear what role the gut microbiota plays in the anti-diabetic activity of HL., Methods: In this study, a type 2 diabetes mellitus (T2DM) mouse model was induced with a six-week high-fat diet (HFD) and a one-time injection of streptozotocin (STZ, 75 mg/kg). One group of these mice was administrated HL (50 mg/kg) through oral gavage two weeks after HFD feeding commenced and continued for four weeks; the other mice were given distilled water as disease control. Comprehensive analyses of physiological indices related to glycolipid metabolism, gut microbiota, untargeted metabolome, and hepatic genes expression, function prediction by PICRUSt2 were performed to identify potential mechanism., Results: We found that HL, in addition to decreasing body fat accumulation, effectively improved insulin resistance by stimulating the hepatic insulin-mediated signaling pathway. In comparison with the control group, HL treatment constructed a distinct gut microbiota and bile acid (BA) profile. The HL-treated microbiota was dominated by bacteria belonging to Bacteroides and the Clostridium innocuum group, which were associated with BA metabolism. Based on the correlation analysis, the altered BAs were closely correlated with the improvement of T2DM-related markers., Conclusion: These results indicated that the anti-diabetic activity of HL was achieved, at least partly, by regulating the structure of the gut microbiota and the composition of BAs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Feng, Li, Pan, Luo, Liu, Ding, Wang, Xu, Zhao and Zhang.)

Protectin conjugates in tissue regeneration 1 (PCTR1) is a novel anti-inflammatory and proresolving lipid mediator biosynthesized from docosahexaenoic acid. Excessive activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome and consequent pyroptosis are involved in diverse inflammatory diseases. However, how PCTR1 affects NLRP3 inflammasome activation and pyroptosis are still unclear. Here, we demonstrated that PCTR1 inhibited NLRP3 inflammasome activation and pyroptosis. These results show that PCTR1 dose-dependently inhibited gasdermin D cleavage in lipopolysaccharide (LPS)-primed murine primary macrophages upon nigericin stimulation. Additionally, PCTR1 treatment after LPS priming inhibited caspase-1 activation and subsequent mature interleukin-1β release independent of the nuclear factor-kappa B pathway. PCTR1 exerted its inhibitory effects by blocking NLRP3-apoptosis-associated speck-like protein containing a CARD (ASC) interaction and ASC oligomerization, thereby restricting NLRP3 inflammasome assembly. However, the inhibitory effect of PCTR1 could be reversed by KH7 and H89, which are the inhibitors of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway. Moreover, PCTR1 treatment alleviated lung tissue damage and improved mouse survival in LPS-induced sepsis. Our study unveils the molecular mechanism of negative regulation of NLRP3 inflammasome activation and pyroptosis by a novel lipid mediator and suggests that PCTR1 may serve as a potential treatment option for NLRP3-inflammasome driven diseases., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Compact diode-pumped continuous wave (CW) and passively Q switched Tm:YAG lasers operating on the 3 H 4 → 3 H 5 transition are demonstrated. Using a 3.5-at.% Tm:YAG crystal, a maximum CW output power of 1.49 W is achieved at 2330 nm with a slope efficiency of 10.1%. The first Q switched operation of the mid-infrared Tm:YAG laser around 2.3 µm is realized with a few-atomic-layer MoS 2 saturable absorber. Pulses as short as 150 ns are generated at a repetition rate of 190 kHz, corresponding to a pulse energy of 1.07 µJ. Tm:YAG is an attractive material for diode-pumped CW and pulsed mid-infrared lasers emitting around 2.3 µm.

In this Letter, a watt-level laser diode (LD)-pumped ∼2.3-µm (on the 3 H 4 → 3 H 5 quasi-four-level transition) laser is reported based on a 1.5 at.% a-cut Tm:YVO 4 crystal. The maximum continuous wave (CW) output power obtained is 1.89 W and 1.11 W with the maximum slope efficiency of 13.6% and 7.3% (versus the absorbed pump power) for the 1% and 0.5% transmittance of the output coupler, respectively. To the best of our knowledge, the CW output power of 1.89 W we obtained is the highest CW output power amongst the LD-pumped ∼2.3-µm Tm 3+ -doped lasers.

Rationale: Tau hyperphosphorylation and aggregation is considered as a main pathological mechanism underlying Alzheimer's disease (AD). Rose Bengal (RB) is a synthetic dye used for disease diagnosis, which was reported to inhibit tau toxicity via inhibiting tau aggregation in Drosophila. However, it was unknown if RB could produce anti-AD effects in rodents., Objectives: The research aimed to investigate if and how RB could prevent β-amyloid (Aβ) oligomers-induced tau hyperphosphorylation in rodents., Methods and Results: RB was tested in vitro (0.3-1 μM) and prevented Aβ oligomers-induced tau hyperphosphorylation in PC12 cells. Moreover, RB (10-30 mg/kg, i.p.) effectively attenuated cognitive impairments induced by Aβ oligomers in mice. Western blotting analysis demonstrated that RB significantly increased the expression of pSer473-Akt, pSer9-glycogen synthase kinase-3β (GSK3β) and reduced the expression of cyclin-dependent kinase 5 (CDK5) both in vitro and in vivo. Molecular docking analysis suggested that RB might directly interact with GSK3β and CDK5 by acting on ATP binding sites. Gene Ontology enrichment analysis indicated that RB might act on protein phosphorylation pathways to inhibit tau hyperphosphorylation., Conclusions: RB was shown to inhibit tau neurotoxicity at least partially via inhibiting the activity of GSK3β and CDK5, which is a novel neuroprotective mechanism besides the inhibition of tau aggregation. As tau hyperphosphorylation is an important target for AD therapy, this study also provided support for investigating the drug repurposing of RB as an anti-AD drug candidate., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Varying coefficient model (VCM) is extensively used in various scientific fields due to its capability of capturing the changing structure of predictors. Classical mean regression analysis is often complicated in the existence of skewed, heterogeneous and heavy-tailed data. For this purpose, this work employs the idea of model averaging and introduces a novel comprehensive approach by incorporating quantile-adaptive weights across different quantile levels to further improve both least square (LS) and quantile regression (QR) methods. The proposed procedure that adaptively takes advantage of the heterogeneous and sparse nature of input data can gain more efficiency and be well adapted to extreme event case and high-dimensional setting. Motivated by its nice properties, we develop several robust methods to reveal the dynamic close-to-truth structure for VCM and consistently uncover the zero and nonzero patterns in high-dimensional scientific discoveries. We provide a new iterative algorithm that is proven to be asymptotic consistent and can attain the optimal nonparametric convergence rate given regular conditions. These introduced procedures are highlighted with extensive simulation examples and several real data analyses to further show their stronger predictive power compared with LS, composite quantile regression (CQR) and QR methods., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 Informa UK Limited, trading as Taylor & Francis Group.)

Historically, giant panda conservation in China has been compromised by disparate management of protected areas. It is thus crucial to address how giant panda populations can be managed cohesively on a landscape scale, an opportunity offered by China's newly established Giant Panda National Park. Here, we evaluated giant panda populations in a metapopulation context, based on range-wide data from the Fourth National Giant Panda Survey. We delineated metapopulations by geographic range, relative abundance, and relative density and assessed the extent of human disturbance each metapopulation faced. We found density-dependent and disturbance-influenced effects on habitat selection across metapopulations. We determined the main effects faced by each metapopulation regarding area sensitivity, population size, intraspecific competition, and disturbance. To enhance the landscape-scale conservation of giant pandas and various other wildlife across China's national park system, we propose that metapopulation management incorporates population status along with density-dependent and disturbance-related effects on habitat selection.

Extinguishing the previously acquired fear is critical for the adaptation of an organism to the ever-changing environment, a process requiring the engagement of GABA A receptors (GABA A Rs). GABA A Rs consist of tens of structurally, pharmacologically, and functionally heterogeneous subtypes. However, the specific roles of these subtypes in fear extinction remain largely unexplored. Here, we observed that in the medial prefrontal cortex (mPFC), a core region for mood regulation, the extrasynaptically situated, δ-subunit-containing GABA A Rs [GABA A (δ)Rs], had a permissive role in tuning fear extinction in male mice, an effect sharply contrasting to the established but suppressive role by the whole GABA A R family. First, the fear extinction in individual mice was positively correlated with the level of GABA A (δ)R expression and function in their mPFC. Second, knockdown of GABA A (δ)R in mPFC, specifically in its infralimbic (IL) subregion, sufficed to impair the fear extinction in mice. Third, GABA A (δ)R-deficient mice also showed fear extinction deficits, and re-expressing GABA A (δ)Rs in the IL of these mice rescued the impaired extinction. Further mechanistic studies demonstrated that the permissive effect of GABA A (δ)R was associated with its role in enabling the extinction-evoked plastic regulation of neuronal excitability in IL projection neurons. By contrast, GABA A (δ)R had little influence on the extinction-evoked plasticity of glutamatergic transmission in these cells. Altogether, our findings revealed an unconventional and permissive role of extrasynaptic GABA A receptors in fear extinction through a route relying on nonsynaptic plasticity. SIGNIFICANCE STATEMENT The medial prefrontal cortex (mPFC) is one of the kernel brain regions engaged in fear extinction. Previous studies have repetitively shown that the GABA A receptor (GABA A R) family in this region act to suppress fear extinction. However, the roles of specific GABA A R subtypes in mPFC are largely unknown. We observed that the GABA A R-containing δ-subunit [GABA A (δ)R], a subtype of GABA A Rs exclusively situated in the extrasynaptic membrane and mediating the tonic neuronal inhibition, works oppositely to the whole GABA A R family and promotes (but does not suppress) fear extinction. More interestingly, in striking contrast to the synaptic GABA A Rs that suppress fear extinction by breaking the extinction-evoked plasticity of glutamatergic transmission, the GABA A (δ)R promotes fear extinction through enabling the plastic regulation of neuronal excitability in the infralimbic subregion of mPFC. Our findings thus reveal an unconventional role of GABA A (δ)R in promoting fear extinction through a route relying on nonsynaptic plasticity., (Copyright © 2022 the authors.)

In this Letter, the fabrication of large-scale (50.8 mm in diameter) few-layered MoS 2 with physical vapor deposition on sapphire is described. Open-aperture Z-scan technology with a home-made excitation source at 2275 nm was applied to explore its nonlinear saturable absorption properties. The as-grown few-layered MoS 2 membrane possessed a modulation depth of 17% and a saturable intensity of 1.185 MW cm -2 . As a consequence, the deposited MoS 2 membrane was exploited as a saturable absorber to realize a passively Q-switched Tm:YAP laser for the first time, to the best of our knowledge. Pulses as short as 316 ns were generated with a repetition rate of 228 kHz, corresponding to a peak power of 5.53 W. Results confirmed that the two-dimensional layered MoS 2 could be beneficial for mid-infrared photonic applications.

Single crystal metal-free halide perovskites have received great attention in recent years owing to their excellent piezoelectric and ferroelectric properties. However, the nanotoxicity and piezoelectricity within the nanoscale of such materials have yet been reported for the demonstration of practical applications. In this work, the observation of intrinsic piezoelectricity in metal-free perovskite (MDABCO-NH 4 I 3 ) films using piezoresponse force microscopy (PFM) is reported. A cytotoxicity test is also performed on MDABCO-NH 4 I 3 to evaluate its low-toxic nature. The as-synthesized MDABCO-NH 4 I 3 is further integrated into a piezoelectric nanogenerator (PENG). The MDABCO-NH 4 I 3 -based PENG (MN-PENG) exhibits optimal output voltage and current of 15.9 V and 54.5 nA, respectively. In addition, the MN-PENG can serve as a self-powered strain sensor for human-machine interface applications or be adopted in in vitro electrical stimulation devices. This work demonstrates a path of perovskite-based PENG with high performance, low toxicity, and multifunctionality for future advanced wearable sensors and portable therapeutic systems., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: Hypertension or elevated blood pressure (BP) is an important risk factor for aortic dissection (AD); however, few prospective studies on this topic have been published. We investigated the association between hypertension/elevated BP and AD in 2 cohorts and conducted a meta-analysis of published prospective studies, including these 2 studies., Methods: We analyzed data from the J-SHC study (Japan-Specific Health Checkups) and UK Biobank, which prospectively followed up 534 378 and 502 424 participants, respectively. Multivariable Cox regression was used to estimate hazard ratios and 95% CIs for the association of hypertension/elevated BP with AD incidence in the UK Biobank and AD mortality in the J-SHC Study. In the meta-analysis, summary relative risks were calculated with random-effects models. A potential nonlinear dose-response relationship between BP and AD was tested with fractional polynomial models, and the best-fitting second-order fractional polynomial regression model was determined., Results: In the J-SHC study and UK Biobank, there were 84 and 182 ADs during the 4- and 9-year follow-up, and the adjusted hazard ratios of AD were 3.57 (95% CI, 2.17-6.11) and 2.68 (95% CI, 1.78-4.04) in hypertensive individuals, 1.33 (95% CI, 1.05-1.68) and 1.27 (95% CI, 1.11-1.48) per 20-mm Hg increase in systolic BP (SBP), and 1.67 (95% CI, 1.40-2.00) and 1.66 (95% CI, 1.46-1.89) per 10-mm Hg increase in diastolic BP (DBP), respectively. In the meta-analysis, the summary relative risks were 3.07 (95% CI, 2.15-4.38, I 2 =76.7%, n=7 studies, 2818 ADs, 4 563 501 participants) for hypertension and 1.39 (95% CI, 1.16-1.66, I 2 =47.7%, n=3) and 1.79 (95% CI: 1.51-2.12, I 2 = 57.0%, n=3) per 20-mm Hg increase in SBP and per 10-mm Hg increase in DBP, respectively. The AD risk showed a strong, positive dose-response relationship with SBP and even more so with DBP. The risk of AD in the nonlinear dose-response analysis was significant at SBP >132 mm Hg and DBP >75 mm Hg., Conclusions: Hypertension and elevated SBP and DBP are associated with a high risk of AD. The risk of AD was positively dose dependent, even within the normal BP range. These findings provide further evidence for the optimization of BP to prevent AD.

Background: The number of obese people continues to increase worldwide, and obesity-related complications add to every country's health burden. Consequently, new weight-loss medications, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), are attracting increasing attention. This study sought to assess the cost effectiveness for weight loss of 4 GLP-1RAs in adult patients with obesity in the United States., Methods: Four GLP-1RA groups that received Liraglutide (1.8 mg QD), Semaglutide (1.0 mg QW), Dulaglutide (1.5 mg QW), or Exenatide (10 μg BID), and one no-treatment group were compared using a decision-tree model. All the estimated parameters were derived from published articles. Quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs) were adopted as the study endpoints. We analyzed the results with the willingness-to-pay (WTP) threshold, and conducted deterministic and probabilistic sensitivity analyses., Results: The GLP-1RAs produced effective weight-loss results; however, not all the GLP-1RAs were cost effective compared to no treatment based on a WTP threshold of $195000/QALY. Among the 4 GLP-1RAs, Semaglutide provided a cost-effective strategy with an ICER of $135467/QALY. The sensitivity analyses showed that these results are reliable., Conclusions: Among the 4 GLP-1RAs, Semaglutide was the most cost-effective obesity medication., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-200/coif). The authors have no conflict of interests to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Dysregulated GABAergic inhibition in the amygdala has long been implicated in stress-related neuropsychiatric disorders. However, the molecular and circuit mechanisms underlying the dysregulation remain elusive. Here, by using a mouse model of chronic social defeat stress (CSDS), we observed that the dysregulation varied drastically across individual projection neurons (PNs) in the basolateral amygdala (BLA), one of the kernel amygdala subregions critical for stress coping. While persistently reducing the extrasynaptic GABA A receptor (GABA A R)-mediated tonic current in the BLA PNs projecting to the ventral hippocampus (BLA → vHPC PNs), CSDS increased the current in those projecting to the anterodorsal bed nucleus of stria terminalis (BLA → adBNST PNs), suggesting projection-based dysregulation of tonic inhibition in BLA PNs by CSDS. Transcriptional and electrophysiological analysis revealed that the opposite CSDS influences were mediated by loss- and gain-of-function of δ-containing GABA A Rs (GABA A (δ)Rs) in BLA → vHPC and BLA → adBNST PNs, respectively. Importantly, it was the lost inhibition in the former population but not the augmentation in the latter population that correlated with the increased anxiety-like behavior in CSDS mice. Virally mediated maintenance of GABA A (δ)R currents in BLA → vHPC PNs occluded CSDS-induced anxiety-like behavior. These findings clarify the molecular substrate for the dysregulated GABAergic inhibition in amygdala circuits for stress-associated psychopathology., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2021 Science China Press. Published by Elsevier B.V. All rights reserved.)

A novel model-free interaction screening approach called the hybrid metrics is introduced for high-dimensional heterogeneous data analysis. The metrics established based on the variation of conditional joint distribution function are measurements of interaction that include both size and direction. They are robust and can work with many types of response variables, including continuous, discrete, and categorical variables. We can apply the hybrid metrics to effective interaction selection for classification, response index models, and Poisson regression, among others. When dealing with classification, the hybrid metrics are capable of capturing both nonlinear category-general and category-specific interaction effects, providing us with a comprehensive overview and precise discovery of category information. When faced with a continuous response, the hybrid metrics perform fairly well even if the signal strength is weak, behaving as if the true interactions were known. To facilitate implementation, a fast two-stage procedure which naturally and efficiently enforces both strong and weak heredity is advocated. We further demonstrate their superior performances over popular competitors by exhaustive simulations and a SRBCT real data example. Supplementary materials for this article are available online., (© 2021 John Wiley & Sons Ltd.)

Dearomatization of indole is a useful strategy to access indolimines: a motif widely exists in biologically active molecules and natural products. Herein, an efficient method for the dearomatization of 2,3-disubstituted indoles to generate diverse indolimines with tetrasubstituted allenes is described. This work accomplishes dearomatization of 2,3-disubstituted indoles through 1,8-addition of (aza)- para -quinone methides, which are generated in situ from propargylic alcohols. A series of synthetically useful indolimines containing quaternary carbon centers and tetrasubstituted allenes can be accessed in good yields (up to 99%). Additionally, the separability of product isomers, diversified product transformations, and easy scale-up of the reaction demonstrate the potential application of this method.

Aims: Early life stress (ELS) increases the risk of psychiatric diseases such as anxiety disorders and depression in later life. Hyperactivation of the basolateral amygdala (BLA) neurons plays a pivotal role in the pathogenesis of stress-related diseases. However, the functional roles of BLA neurons in ELS-induced anxiety disorders are not completely understood., Main Methods: Mice were subjected to maternal separation (MS) during postnatal days 3 to 21 to mimic ELS. Anxiety-like behavior was tested by open field test (OFT), elevated plus maze (EPM), and novelty suppressed feeding (NSF). Then, c-fos expression, a proxy for neuronal activity, was evaluated by immunofluorescence. Finally, synaptic transmission and intrinsic excitability were measured by whole-cell patch-clamp recordings., Key Findings: MS significantly increased anxiety-like behavior in adulthood, as indicated by less time spent in the center area of the OFT, less time spent in and fewer entries to the open arms of the EPM, and increased latency to feed in NSF. Mechanistically, MS increased the expression of c-fos in BLA. MS enhanced the excitatory, but not inhibitory, synaptic transmission onto BLA projection neurons (PNs), which was caused by enhanced presynaptic glutamate release. Moreover, MS also markedly increased the intrinsic neuronal excitability of BLA PNs, probably due to the reduced medium afterhyperpolarization (mAHP) in BLA PNs., Significance: Our results suggest that the changes of neuronal activity and synaptic transmission in the BLA PNs may play a crucial role in ELS-induced anxiety-like behavior, and these findings provide new insights into the pathological mechanisms of stress-related anxiety disorders., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Two-dimensional (2D) tin halide perovskites have recently emerged as very promising materials for eco-friendly lead-free photovoltaic devices. However, the fine control of the bulky organic cations orderly embedding into the perovskite structure with a narrow quantum-well width distribution and favorable orientation is rather complicated. In this study, we proposed to introduce the F-substituted phenylethlammonium (PEA) cation ( i.e. , 4-fluorophenethylammonium FPEA) in 2D tin halide perovskite, which may mitigate phase polydispersity and crystal orientation, thus potentially increasing attainable charge-carrier mobility. A strong interlayer electrostatic attraction between electron-deficient F atoms and its adjacent phenyl rings aligns the crystal structure, working together with the validated dipole interaction. Therefore, the fluorination of organic cation leads to orderly self-assembly of solvated intermediates and promotes vertical crystal orientation. Furthermore, the interlayer electrostatic interaction serves as a supramolecular anchor to stabilize the 2D tin halide perovskite structure. Our work uncovers the effect of interlayer molecular interaction on efficiency and stability, which contributes to the development of stable and efficient low-toxicity perovskite solar cells.

The central spindle spatially and temporally regulates the formation of division plane during cytokinesis in animal cells. The heterotetrameric centralspindlin complex bundles microtubules to assemble the central spindle, the mechanism of which is poorly understood. Here, we determined the crystal structures of the molecular backbone of ZEN-4/CYK-4 centralspindlin from Caenorhabditis elegans , which revealed the detailed mechanism of complex formation. The molecular backbone of centralspindlin has the intrinsic propensity to undergo liquid-liquid phase separation. The condensation of centralspindlin requires two patches of basic residues at ZEN-4 and multiple acidic residues at the intrinsically disordered region of CYK-4, explaining the synergy of the two subunits for the function. These complementary charged residues were critical for the microtubule bundling activity of centralspindlin in vitro and for the assembly of the central spindle in vivo. Together, our findings provide insights into the mechanism of central spindle assembly mediated by centralspindlin through charge-driven macromolecular condensation., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Background: Endothelial glycocalyx loss is integral to increased pulmonary vascular permeability in sepsis-related acute lung injury. Protectin conjugates in tissue regeneration 1 (PCTR1) is a novel macrophage-derived lipid mediator exhibiting potential anti-inflammatory and pro-resolving benefits., Methods: PCTR1 was administrated intraperitoneally with 100 ng/mouse after lipopolysaccharide (LPS) challenged. Survival rate and lung function were used to evaluate the protective effects of PCTR1. Lung inflammation response was observed by morphology and inflammatory cytokines level. Endothelial glycocalyx and its related key enzymes were measured by immunofluorescence, ELISA, and Western blot. Afterward, related-pathways inhibitors were used to identify the mechanism of endothelial glycocalyx response to PCTR1 in mice and human umbilical vein endothelial cells (HUVECs) after LPS administration., Results: In vivo, we show that PCTR1 protects mice against lipopolysaccharide (LPS)-induced sepsis, as shown by enhanced the survival and pulmonary function, decreased the inflammatory response in lungs and peripheral levels of inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and interleukin-1β. Moreover, PCTR1 restored lung vascular glycocalyx and reduced serum heparin sulphate (HS), syndecan-1 (SDC-1), and hyaluronic acid (HA) levels. Furthermore, we found that PCTR1 downregulated heparanase (HPA) expression to inhibit glycocalyx degradation and upregulated exostosin-1 (EXT-1) protein expression to promote glycocalyx reconstitution. Besides, we observed that BAY11-7082 blocked glycocalyx loss induced by LPS in vivo and in vitro, and BOC-2 (ALX antagonist) or EX527 (SIRT1 inhibitor) abolished the restoration of HS in response to PCTR1., Conclusion: PCTR1 protects endothelial glycocalyx via ALX receptor by regulating SIRT1/NF-κB pathway, suggesting PCTR1 may be a significant therapeutic target for sepsis-related acute lung injury.

Background: Adequate water intake in pregnant women plays an important role in their health and in fetal growth and development. However, there is insufficient applicable data to guide and evaluate the water intake of pregnant women in China. Based on a nationwide sample of pregnant women, we mainly aimed to investigate the daily total water intake (TWI) and the contribution of different beverages and food sources to the TWI, to assess the percentage of participants who comply with the adequate intake (AI) value of water set by the Chinese Nutrition Society (CNS) and the European Food Safety Authority (EFSA) and to analyze the contribution of different water sources to the daily total energy intake (TEI)., Methods: A multi-stage sampling method was used to recruit pregnant women from 11 provinces and two municipalities in China. A 4-day online diary with a food atlas was used to assess water and dietary intake. Finally, 653 pregnant women were included in the analysis. The Mann-Whitney U test and the independent-sample t-test were used to compare the differences between related variables in different age groups or different gestational periods, and partial correlation was used to explore the correlation between water and energy intake., Results: The median daily TWI of pregnant women was 2190 mL, of which water from beverages and foods accounted for 52.9% and 47.1%, respectively. Approximately 80.5% of the water from beverages was mainly from plain water ( r = 0.973), while in the part of the water from foods, dishes (32.4%) were the main contributors ( r = 0.663). Only 16.4% and 43.8% of the total population met the TWI recommendation set by the CNS and EFSA, respectively. Among these, the contribution of the water from beverages was higher than that of the water from food. For those whose TWI did not reach the recommended level, the contribution of the water from beverages was almost equal to that of food. The median daily TEI of pregnant women was 1589 kcal, of which beverages accounted for 9.7%. Milk and milk derivatives (71.3%) were the main contributors to energy from beverages, accounting for 71.3% ( r = 0.444). Although sugar-sweetened drinks only accounted for 10.1% of the energy from beverages, they were highly correlated with energy from beverages ( r = 0.836). Through grouping analysis, age and gestational period had no significant effect on the above main results., Conclusions: This was the beginning of a nationwide study on the TWI of pregnant women in China, and the results provide evidence of the need for interventions to improve water intake among pregnant women and the revision of reference values for AI of TWI in pregnant women in China.

Numerous natural phytochemicals such as resveratrol are acknowledged as potent botanical agents in regulating immune responses. However, it is less understood whether such immunomodulatory phytochemicals are appropriate for use as direct treatments in veterinary viral diseases. In the present study, we investigated the efficacy of resveratrol in suppressing vesicular stomatitis virus (VSV) infection. Outbreaks of VSV can cause massive economic loss in poultry and livestock husbandry farming, and VSV treatment is in need of therapeutic development. We utilized a recombinant VSV that expresses green fluorescent protein (GFP) to measure viral replication in cells treated with resveratrol. Our findings revealed that resveratrol treatment affords a protective effect, shown by increased viability and reduced viral replication, as indicated by a reduction in fluorescent signals. Additionally, we found that resveratrol inhibition of VSV infection occurs via suppression of the caspase cascade. Structural analysis also indicated that resveratrol potentially interacts with the active sites of caspase-3 and -7, facilitating antiviral activity. The potential effect of resveratrol on reducing VSV infection in vitro suggests that resveratrol should be further investigated as a potential veterinary therapeutic or prophylactic agent.