Ectopic Expression of TIGIT in Lung Adenocarcinoma and Its Clinical Significance.

This study aimed to investigate the T cell immunoreceptor with ITIM and Ig domains (TIGIT) expression in lung adenocarcinoma (LUAD). TIGIT expression was measured by western blot, reverse transcription quantitative polymerase chain reaction. Seventy-two paired surgical specimens were collected from patients with stage I-IV LUAD. The expression of TIGIT in surgical specimens was determined using immunohistochemistry. TIGIT was overexpressed in LUAD tissues. Moreover, overexpressed TIGIT was significantly associated with advanced clinical staging, lymph node metastasis, distant metastasis, and TP53 mutations in LUAD. Moreover, high expression of TIGIT was negatively correlated with purity of CD4+ T cells. High rations of TIGIT+CD4+ T cells predicted poor overall survival of LUAD patients. Additionally, high ratios of TIGIT+CD4+ T cells is closely related to CD4+ T cell depletion. Taken together, TIGIT was overexpressed in LUAD patients. High levels of TIGIT induced the alteration of CD4+ T cell based immunomodulation and predicted poor prognosis of LUAD patients. Therefore, TIGIT can be potential biomarker for LUAD.

Perisaccadic and attentional remapping of receptive fields in lateral intraparietal area and frontal eye fields.

The nature and function of perisaccadic receptive field (RF) remapping have been controversial. We use a delayed saccade task to reduce previous confounds and examine the remapping time course in the lateral intraparietal area and frontal eye fields. In the delay period, the RF shift direction turns from the initial fixation to the saccade target. In the perisaccadic period, RFs first shift toward the target (convergent remapping), but around the time of saccade onset/offset, the shifts become predominantly toward the post-saccadic RF locations (forward remapping). Thus, unlike forward remapping that depends on the corollary discharge (CD) of the saccade command, convergent remapping appears to follow attention from the initial fixation to the target. We model the data with attention-modulated and CD-gated connections and show that both sets of connections emerge automatically in neural networks trained to update stimulus retinal locations across saccades. Our work thus unifies previous findings into a mechanism for transsaccadic visual stability.

Distributions of Visual Receptive Fields from Retinotopic to Craniotopic Coordinates in the Lateral Intraparietal Area and Frontal Eye Fields of the Macaque.

Even though retinal images of objects change their locations following each eye movement, we perceive a stable and continuous world. One possible mechanism by which the brain achieves such visual stability is to construct a craniotopic coordinate by integrating retinal and extraretinal information. There have been several proposals on how this may be done, including eye-position modulation (gain fields) of retinotopic receptive fields (RFs) and craniotopic RFs. In the present study, we investigated coordinate systems used by RFs in the lateral intraparietal (LIP) cortex and frontal eye fields (FEF) and compared the two areas. We mapped the two-dimensional RFs of neurons in detail under two eye fixations and analyzed how the RF of a given neuron changes with eye position to determine its coordinate representation. The same recording and analysis procedures were applied to the two brain areas. We found that, in both areas, RFs were distributed from retinotopic to craniotopic representations. There was no significant difference between the distributions in the LIP and FEF. Only a small fraction of neurons was fully craniotopic, whereas most neurons were between the retinotopic and craniotopic representations. The distributions were strongly biased toward the retinotopic side but with significant craniotopic shifts. These results suggest that there is only weak evidence for craniotopic RFs in the LIP and FEF, and that transformation from retinotopic to craniotopic coordinates in these areas must rely on other factors such as gain fields.

Novel insights into the effects of 5-hydroxymethfurural on genomic instability and phenotypic evolution using a yeast model.

5-Hydroxymethfurural (5-HMF) is naturally found in a variety of foods and beverages and represents a main inhibitor in the lignocellulosic hydrolysates used for fermentation. This study investigated the impact of 5-HMF on the genomic stability and phenotypic plasticity of the yeast Saccharomyces cerevisiae. Using next-generation sequencing technology, we examined the genomic alterations of diploid S. cerevisiae isolates that were subcultured on a medium containing 1.2 g/L 5-HMF. We found that in 5-HMF-treated cells, the rates of chromosome aneuploidy, large deletions/duplications, and loss of heterozygosity were elevated compared with that in untreated cells. 5-HMF exposure had a mild impact on the rate of point mutations but altered the mutation spectrum. Contrary to what was observed in untreated cells, more monosomy than trisomy occurred in 5-HMF-treated cells. The aneuploidy mutant with monosomic chromosome IX was more resistant to 5-HMF than the diploid parent strain because of the enhanced activity of alcohol dehydrogenase. Finally, we found that overexpression of ADH6 and ZWF1 effectively stabilized the yeast genome under 5-HMF stress. Our findings not only elucidated the global effect of 5-HMF on the genomic integrity of yeast but also provided novel insights into how chromosomal instability drives the environmental adaptability of eukaryotic cells.IMPORTANCESingle-cell microorganisms are exposed to a range of stressors in both natural and industrial settings. This study investigated the effects of 5-hydroxymethfurural (5-HMF), a major inhibitor found in baked foods and lignocellulosic hydrolysates, on the chromosomal instability of yeast. We examined the mechanisms leading to the distinct patterns of 5-HMF-induced genomic alterations and discovered that chromosomal loss, typically viewed as detrimental to cell growth under most conditions, can contribute to yeast tolerance to 5-HMF. Our results increased the understanding of how specific stressors stimulate genomic plasticity and environmental adaptation in yeast.

Perisaccadic and Attentional Remapping of Receptive Fields in Lateral Intraparietal Area and Frontal Eye Fields.

The nature and function of perisaccadic receptive-field (RF) remapping have been controversial. We used a delayed saccade task to reduce previous confounds and examined the remapping time course in areas LIP and FEF. In the delay period, the RF shift direction turned from the initial fixation to the saccade target. In the perisaccadic period, RFs first shifted toward the target (convergent remapping) but around the time of saccade onset/offset, the shifts became predominantly toward the post-saccadic RF locations (forward remapping). Thus, unlike forward remapping that depends on the corollary discharge (CD) of the saccade command, convergent remapping appeared to follow attention from the initial fixation to the target. We modelled the data with attention-modulated and CD-gated connections, and showed that both sets of connections emerged automatically in neural networks trained to update stimulus retinal locations across saccades. Our work thus unifies previous findings into a mechanism for transsaccadic visual stability.

Two Species of Stemphylium, S. astragali and S. henanense sp. nov., Causing Leaf and Stem Spot Disease on Astragalus sinicus in China.

Astragalus sinicus is a versatile legume crop, primarily utilized as a green manure in China. During 2020 and 2021, A. sinicus plants exhibiting dark brown or reddish-brown lesions or spots on leaves and stems were collected from fields in the Henan, Sichuan, and Guangxi provinces of China. Sixteen single-spore isolates were isolated from the infected leaf and stem tissue samples. Phylogenetic analyses based on the concatenated internal transcribed spacer, gapdh, and cmdA sequences indicated that 14 of them belong to Stemphylium astragali, whereas two isolates can be well separated from other known species in this genus. Based on the morphological characteristics and nucleotide polymorphisms with sister taxa, the two isolates were identified as a new species named S. henanense. Furthermore, pathogenicity assays showed that the S. astragali and S. henanense isolates caused leaf and stem spot symptoms on A. sinicus. Altogether, we describe a new species of Stemphylium (i.e., S. henanense sp. nov.) causing leaf spot disease of A. sinicus. In addition, this is the first report of S. astragali causing stem spot disease of A. sinicus.

First Report of Leaf Spot Disease Caused by Boeremia linicola on Trifolium repens in China.

Trifolium repens L. (White clover) a multipurpose legume crop, primarily utilized as a green manure in China. In March 2018, field investigations showed that a leaf spot disease occurred on T. repens in three fields with 50% to 80% incidence (50 plants in each field were investigated) in Nanchong City, Sichuan Province of China. Infected leaves showed symptoms of irregular dark brown spots in the center of leaves or at the leaf margins. Symptomatic leaves were surface sterilized with 3% NaClO for 3 min followed by 75% ethanol for 30 s and then rinsed in sterile water three times. Thereafter, tissue samples from margins of individual lesions were placed on potato dextrose agar and incubated at 25°C in the dark. Four pure cultures (Y3-1; Y3-2; Y3-3; Y3-4) were obtained by single spore isolation. On oatmeal agar medium, a colony reached 57 mm diameter after 9 d in alternating light and dark at 25℃. Fimbriate aerial hypha were flat and compact with pale brown to dark brown color. Conidiogenous cells were hyaline, smooth, ampulliform to doliiform (n = 30), ranging from 4.1 to 10.5 µm long (6.6 ± 1.8 µm) × 2.2 to 5.7 µm wide (4.1 ± 0.8 µm). Conidia were ellipsoidal to cylindrical, hyaline, thin walled, smooth, aseptate, with 2 to 4 polar guttules (n = 50), ranging from 3.2 to 11.3 µm long (6.3 ± 1.1 µm) × 2.1 to 4.1 µm wide (2.8 ± 0.4 µm). Conidial matrix was whitish. Morphologically these isolates resembled species in Boeremia (Chen et al. 2015). Genomic DNA of each culture was extracted from mycelia using the quick and safe method (Chi et al. 2009). The 28S large subunit of nuclear ribosomal RNA (LSU) region, internal transcribed spacer (ITS) region, RNA polymerase II second largest subunit (RPB2), translation elongation factor 1-α (TEF 1-α), ß-Tubulin (TUB2) were amplified with corresponding primers (Carbone and Kohn 1999; Liu et al. 1999; Rehner and Samuels 1994; Sung et al. 2007; Vilgalys and Hester 1990; White et al. 1990; Woudenberg et al.2009). Sequences were deposited in GenBank with accession numbers: ON705759 to ON705766, ON734043 to ON734046 and ON841585 to ON841592. Phylogenetic analysis was conducted with combined sequences of the five loci using the maximum likelihood (ML) and the maximum parsimony (MP) methods. The four isolates and the extype strain of B. linicola (CBS 116.76) clustered together with high bootstrap support (BS) values (MLBS = 100; MPBS = 98). All sequences showed 100% identity to those of CBS 116.76, except the ITS region of our isolates (ON705759 to ON705762), which show 99.6% identity to that of CBS 116.76. Based on morphological characteristics and phylogenetic results, our isolates were identified as B. linicola, although the morphological characteristics of CBS 116.76 had not been characterized. To assess pathogenicity, a conidial suspension (approximately 105 CFU/mL) of isolate Y3-1 was sprayed on 1-month-old healthy plants in a greenhouse at 22℃ to 28℃. Plants sprayed with sterilized water were used as negative controls. The test was conducted three times, each with 3 plants. After 10 days, the leaves of the plants showed irregular brown lesions that were similar to the symptoms observed in the field, control plants remained healthy. The pathogen was reisolated and confirmed to be B. linicola, thus completing the verification of Koch's Postulates. Compared to B. exigua, a causal pathogen associated with leaf spot on white clover reported by Wang et al (Wang et al. 2021), B. linicola produced larger conidia, and the two species did not cluster together in the phylogenetic tree. To our knowledge, this is the first report of leaf spot disease caused by B. linicola on Trifolium repens in China.

First Report of Pyricularia oryzae Causing Blast on Palm Grass in China.

Palm grass (Setaria palmifolia) has been used as an ornamental plant and vegetable crop (Wu, 2009; Plarre, 1995). In June 2019, 2-10 mm severe leaf lesions with gray centers and brown-yellow edges were observed on the leaves of palm grass in Liuyang city (28°43'N, 114°12'E), Hunan province, China (Fig. 1A). Disease incidence on leaves was 20 - 40%. The infected leaves were collected and disinfected with 75% alcohol for 30 sec and 1% sodium hypochlorite for 1 min, followed by three rinses in sterilized ddH2O, dried on sterilized filter paper, and incubated on water agar for 48 h under continuous fluorescent light at 26℃. Then, typical pyriform and 2-septate conidia (23.97 - 30.37 × 7.42 - 9.98 µm, N = 30) appeared at the lesions (Fig. 1B). Four single-spore were captured, and then grew on oatmeal tomato agar for seven days under continuous fluorescent light at 26℃ to obtain four isolates (LY-ZY-7a, -7b, -9b and -9c) and produce conidia for inoculation tests. The colony morphology of LY-ZY-7b on OTA was gray and floccose, and the growth rate was 6.15 - 6.31 mm/d at 26 °C (Fig. 1C). Spores of LY-ZY-7b were washed off with sterilized ddH2O plus 0.025% Tween-20 to make spore suspensions. For scratch inoculation, 10 µL spore suspension (1 × 105 spores/mL) was inoculated on the wound scratched with a sterilized pin along the vein (3 mm × 3 mm) on palm grass middle leaf of 4-week-old seedlings. The inoculated leaves were sealed in a 15-cm Petri dish. For spray inoculation, 20 mL spore suspension (5 × 104 spores/mL) was made and sprayed on ten healthy palm grasses of 4-week-old seedlings. Plants used as negative controls were sprayed with sterilized ddH2O plus 0.025% Tween-20 (Liu et al. 2022; Zhang et al. 2014). After inoculation, all plants were put into transparent boxes to maintain > 95% humidity and covered with black plastic bags for one day. Then, the boxes containing the plants were placed in a growth chamber at 26°C (12 h light / 12 h darkness photoperiod). After six days, typical blast-type lesions with brown-yellow edges were visible on the leaves. Control plants did not show symptoms (Fig. 1D, 1E). Microscopical examination showed that the conidia and conidiophore recovered from the lesion of the inoculated plants have the same morphology as those recovered from natural infected tissues (Fig. 1F, 1G). The colony morphology of the pathogen isolated from the artificially inoculated tissue was consistent with that of isolate LY-ZY-7b (Fig. 1C). The spore suspension (5 × 104 spores/mL) of isolate LY-ZY-7b and one rice-infecting strain P131 (Yang et al., 2010) was made and sprayed onto 4-week-old seedlings of three rice cultivars. But unfortunately, isolate LY-ZY-7b could not cause any disease lesions on the tested rice cultivars, whereas strain P131 produced many typical blast lesions on rice leaves (Fig. 1H). Then, the fungal genetic identity of four isolates (LY-ZY-7a, -7b, -9b, and -9c) was confirmed by comparison of the sequence obtained from partial DNA of Actin (ACT), ITS, and RPB1 loci from our isolates and those previously published by Klaubauf et al. 2014. The nucleotide sequences of ACT, ITS, and RPB1 were submitted to GenBank ON228695-ON228697 (ACT), ON210978-ON210980 (ITS), ON228698-ON228701 (RPB1). A phylogenetic tree deduced from a maximum likelihood analysis based on combined ACT-ITS-RPB1 sequence data of Pyricularia showed that these four isolates (LY-ZY-7a, -7b, -9b, and -9c) clustered together on Pyricularia oryzae, with a high bootstrap support value (Fig. 2). Based on morphological characteristics and molecular phylogeny, these four isolates were identified as P. oryzae (Klaubauf et al. 2014; Qi et al. 2019). To our knowledge, this is the first report of blast disease on palm grass caused by P. oryzae in China, which will help develop disease management strategies against palm grass blast. Moreover, as a host of P. oryzae, palm grass might contribute as an inoculum source for blast diseases on cereal crops (such as rice, wheat, and barley) caused by P. oryzae in the field.

A generic and rapid analytical method for comprehensive determination of veterinary drugs and other contaminants in raw honey.

A generic, rapid, simple and low-cost analytical method for simultaneously screening and confirming 400 veterinary drugs and other contaminants in raw honey was developed. The method was based on one-step extraction and ultra-high performance liquid chromatography coupled with electrospray ionization and tandem mass spectrometry. A well-designed extraction method results in the complete precipitation of proteins and separation of analytes from carbohydrates and reduces the time and cost of analysis by covering polar to non-polar analytes. Optimized pretreatment processes lead to no significant interference on analysis from complicated sample matrix. Competent linearity was found for all of target compounds with linear regression coefficients (R) higher than 0.99. Detection limits ranged from 0.05 µg/kg to 10 µg/kg. Average recovery rates spiked in raw honey and ranged from 57.3% to 139.8%, and associated relative standard deviation values ranged from 0.4% to 25.2% under selected conditions. The extraction sensitivity, linearity, recovery, and precision of the method were validated. The results clearly demonstrated the feasibility of using this approach in raw honey purchase. The application of this method, which improved efficiency and the coverage of residues, may considerably reduce effort and time in routine monitoring programs.

Computational modeling of excitatory/inhibitory balance impairments in schizophrenia.

Deficits in glutamatergic function are well established in schizophrenia (SZ) as reflected in "input" dysfunction across sensory systems. By contrast, less is known about contributions of the GABAergic system to impairments in excitatory/inhibitory balance. We investigated this issue by measuring contrast thresholds for orientation detection, orientation discriminability, and orientation-tilt-aftereffect curves in schizophrenia subjects and matched controls. These measures depend on the amplitude and width of underlying orientation tuning curves, which, in turn, depend on excitatory and inhibitory interactions. By simulating a well-established V1 orientation selectivity model and its link to perception, we demonstrate that reduced cortical excitation and inhibition are both necessary to explain our psychophysical data. Reductions in GABAergic feedback may represent a compensatory response to impaired glutamatergic input in SZ, or a separate pathophysiological event. We also found evidence for the widely accepted, but rarely tested, inverse relationship between orientation discriminability and tuning width.

Cross-fixation interactions of orientations suggest high-to-low-level decoding in visual working memory.

Sensory encoding (how stimuli evoke sensory responses) is known to progress from low- to high-level features. Decoding (how responses lead to perception) is less understood but is often assumed to follow the same hierarchy. Accordingly, orientation decoding must occur in low-level areas such as V1, without cross-fixation interactions. However, a study, Ding, Cueva, Tsodyks, and Qian (2017), provided evidence against the assumption and proposed that visual decoding may often follow a high-to-low-level hierarchy in working memory, where higher-to-lower-level constraints introduce interactions among lower-level features. If two orientations on opposite sides of the fixation are both task relevant and enter working memory, then they should interact with each other. We indeed found the predicted cross-fixation interactions (repulsion and correlation) between orientations. Control experiments and analyses ruled out alternative explanations such as reporting bias and adaptation across trials on the same side of the fixation. Moreover, we explained the data using a retrospective high-to-low-level Bayesian decoding framework.

Tuning curves vs. population responses, and perceptual consequences of receptive-field remapping.

Sensory processing is often studied by examining how a given neuron responds to a parameterized set of stimuli (tuning curve) or how a given stimulus evokes responses from a parameterized set of neurons (population response). Although tuning curves and the corresponding population responses contain the same information, they can have different properties. These differences are known to be important because the perception of a stimulus should be decoded from its population response, not from any single tuning curve. The differences are less studied in the spatial domain where a cell's spatial tuning curve is simply its receptive field (RF) profile. Here, we focus on evaluating the common belief that perrisaccadic forward and convergent RF shifts lead to forward (translational) and convergent (compressive) perceptual mislocalization, respectively, and investigate the effects of three related factors: decoders' awareness of RF shifts, changes of cells' covering density near attentional locus (the saccade target), and attentional response modulation. We find that RF shifts alone produce either no shift or an opposite shift of the population responses depending on whether or not decoders are aware of the RF shifts. Thus, forward RF shifts do not predict forward mislocalization. However, convergent RF shifts change cells' covering density for aware decoders (but not for unaware decoders) which may predict convergent mislocalization. Finally, attentional modulation adds a convergent component to population responses for stimuli near the target. We simulate the combined effects of these factors and discuss the results with extant mislocalization data. We speculate that perisaccadic mislocalization might be the flash-lag effect unrelated to perisaccadic RF remapping but to resolve the issue, one has to address the question of whether or not perceptual decoders are aware of RF shifts.

Recombinant human adenovirus type 5 (Oncorine) reverses resistance to immune checkpoint inhibitor in a patient with recurrent non-small cell lung cancer: A case report.

Immune checkpoint inhibitors (ICIs) have shown significant efficacy in various solid tumors, but only a small subgroup of patients benefit from them because of immune resistance. Oncorine (formerly H101), a recombinant human adenovirus type 5, has direct anticancer properties and enhances cell-mediated immune responses. At present, few studies on the role of Oncorine in reversing resistance to ICIs have been reported. Here, we present a case with recurrent non-small cell lung cancer (NSCLC). The patient developed resistance to nivolumab therapy. After trying immunotherapy plus chemotherapy or antiangiogenesis therapy, the patient only obtained a transient response. The patient then received experimental treatment with Oncorine together with nivolumab and anlotinib. She experienced symptomatic improvement with a performance status score of 1, and achieved stable disease despite partial lung tissue necrosis. This was a successful exploration of oncolytic viruses reversing immune resistance.

The Effect of Torsional Vibration in Longitudinal-Torsional Coupled Ultrasonic Vibration-Assisted Grinding of Silicon Carbide Ceramics.

Rotary longitudinal-torsional coupled ultrasonic vibration-assisted grinding (LTUAG) is a new manufacturing method that can improve the grinding ability of silicon carbide ceramics. However, compared with longitudinal ultrasonic vibration-assisted grinding (LUAG), the role of torsional vibration in the grinding process is unclear. In this study, an effective method for measuring longitudinal-torsional coupled ultrasonic vibration amplitude and an experimental setup for measuring actual amplitude during grinding are proposed. The trajectory of the abrasive grains under the same grinding parameters and the same longitudinal amplitude during LTUAG and LUAG are analysed. Ultrasonic amplitude curves under the condition of tool rotation are then measured and analysed. Finally, the effect of torsional vibration on grinding force and surface roughness under the same grinding conditions is explained. Experimental analysis shows that the introduction of torsional vibration has little effect on the trajectory length and does not change the number of interference overlaps between abrasive grain tracks. Torsional vibration will only increase the cutting speed during grinding and reduce the undeformed chip thickness, which will reduce the grinding force and improve the surface roughness of LTUAG.

Oxidative stress caused by a dysregulated Wnt/ß-catenin signalling pathway is involved in abnormal placenta formation in pregnant mice with chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is characterized by extreme fatigue and disabling symptoms. Women with CFS often have a high risk of gynaecological problems such as irregular menstruation, endometriosis and pelvic pain and sexual dysfunction. Our previous results have shown that, in pregnant mice, CFS significantly decreased the progestational hormone level in serum, as well as learning and memory, and the function of the hypothalamus-pituitary-gonadal axis. In addition, the F1 generation also suffered from congenital hypothyroidism. At present, there has been no report about placenta formation and embryonic development in pregnant mice with CFS. The aim of the present study was to investigate the influence of CFS on the morphology, oxidative stress and Wnt/ß-catenin signalling pathway during placenta formation. In this study, we found that CFS decreased the number of implantation sites for blastocysts, and increased the number of absorbed, stillborn and malformed fetuses. The morphology and structure of the placenta were abnormal in pregnant mice with CFS. Further study found that the oxidative stress in serum, uterus and placenta was increased in pregnant mice with CFS, while the levels of antioxidase were decreased. CFS also inhibited the Wnt/ß-catenin signalling pathway in the placenta. These results suggested that inhibition of the Wnt/ß-catenin signalling pathway and enhanced oxidative stress play an important role in abnormal placentation in pregnant mice with CFS.

The efficacy and safety of moxibustion for chemotherapy-induced gastrointestinal adverse reaction: A protocol for systematic review and meta-analysis.

BACKGROUND: Many cancer patients experience gastrointestinal adverse reaction during chemotherapy. Pharmacological interventions are commonly used to treat chemotherapy-induced gastrointestinal side effects but have various limitations. Clinical trials have indicated that moxibustion may alleviate gastrointestinal dysfunction and improve quality of life (QoL) after chemotherapy. This study aims to assess the efficacy and safety of moxibustion for chemotherapy-induced gastrointestinal adverse reaction through a systematic review and meta-analysis. METHODS: All randomized controlled trials (RCTs) related to moxibution targeting chemotherapy-induced gastrointestinal adverse reaction will be searched in online databases, such as PubMed, EMBASE, the Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), the Chinese Scientific Journal Database (VIP Database) and WanFang Database from their inception to May 1, 2020. The primary outcome is the incidence and severity of chemotherapy-related gastrointestinal toxicities (nausea and vomiting, diarrhea and constipation). The secondary outcomes include the quality of life, biological parameters' alteration, and adverse events. Study selection, data extraction, and assessment of risk of bias will be performed independently by 2 researchers. The Cochrane Collaboration's Review Manager (RevMan 5.3) software will be used to conduct the direct meta-analysis. RESULTS: This study will provide a comprehensive review of the available evidence for the treatment of chemotherapy-induced gastrointestinal adverse reaction with moxibustion. CONCLUSION: The conclusion of this study will provide evidence to judge whether moxibustion is an effective and safety therapeutic intervention for chemotherapy-induced gastrointestinal adverse reaction. PROSPERO REGISTRATION NUMBER: CRD42020182990.

The onset of sleep disturbances and their associations with anxiety after acute high-altitude exposure at 3700 m.

Sleep disturbances and psychiatric repercussions pose great challenges at high altitude; however, few studies have investigated sleep disturbance and anxiety profiles and their associations after acute exposure in consecutive patients. Thus, we aimed to study the profiles of sleep disturbances in consecutive patients after high-altitude exposure and the association of such disturbances with anxiety. A total of 668 participants were recruited at sea level and 3700 m. The trials were performed at sea level (1 week prior to a 2-h flight to a high-altitude destination) and at 3700 m (24, 72, and 168 h). Sleep disturbances were assessed by self-reported sleep patterns and scores on the Athens Insomnia Scale (AIS). State anxiety was assessed using the Self-Rating Anxiety Scale (SAS). In our study, the incidence of sleep disturbances increased significantly after acute high-altitude exposure (65.3%, 434/668) and then gradually decreased after 72 h (50%, 141/282) and 168 h (44%, 124/282). The sleep assessments AIS [2.0 (4.0) vs. 4.0 (5.0)] and ESS [4.0 (4.0) vs. 5.0 (5.0)] increased significantly (p < 0.05). Also, the SAS increased significantly from 26.25 (3.75) to 28.75 (7.5). The SAS was significantly high in sleep disturbance group [31.25 (7.5) vs. 27.5 (5), p < 0.001] than in the non-sleep- disturbance group. The baseline SAS and AIS scores were significantly higher in participants with sleep disturbances than in those without (p < 0.01). Age, baseline insomnia, sleepiness, fatigue, and higher SAS were predictors of sleep disturbances in univariate regression (all p values < 0.05). However, only an older age (p = 0.045) and a higher baseline SAS (p = 0.018) remained independent predictors of sleep disturbances. Our findings indicated that acute high-altitude exposure triggers the onset of sleep disturbances, which are closely associated with anxiety. Furthermore, baseline state anxiety and age are independent predictors of sleep disturbances at high altitude.

QiShenYiQi Pills® ameliorates ischemia/reperfusion-induced myocardial fibrosis involving RP S19-mediated TGFß1/Smads signaling pathway.

QiShenYiQi Pills (QSYQ) is a compound Chinese medicine widely used in China for treatment of cardiovascular disease. However, limited data are available regarding the anti-fibrotic role of QSYQ after ischemia/reperfusion (I/R) injury. This study aimed to investigate the effect of post-treatment with QSYQ on myocardial fibrosis after I/R-induced myocardium injury, and the role of different compounds of QSYQ, focusing especially on the involvement of chemokine ribosomal protein S19 (RP S19) dimer and monocyte migration. Male Sprague-Dawley rats were subjected to left anterior descending coronary artery occlusion for 30 min followed by reperfusion with or without administration of QSYQ (0.6, 1.2, or 1.8 g/kg) once daily by gavage for 6 days. Post-treatment with QSYQ diminished I/R-induced infarct size, alleviated myocardium injury, attenuated myocardial fibrosis after 6 days of reperfusion, and restored heart function and myocardial blood flow after I/R. In addition, the drug significantly inhibited monocyte infiltration and macrophage polarization towards M2, which was attributable to chemokine RP S19 dimer. Moreover, Western blots revealed that QSYQ blocked I/R-induced increase in TGFß1 and TGFßRⅡ and reversed its relevant gene expression, such as Smad3,4,6,7, and inhibited the increase of MMP 2,9 expression. As the major components of QSYQ, astragaloside IV (AsIV), 3,4-dihydroxy-phenyl lactic acid (DLA), and notoginsenoside R1 (R1) were assessed as to the contribution of each of them to the expression of the proteins concerned. The results showed that the effect of AsIV was similar to QSYQ, while DLA and R1 only partly simulated the effect of QSYQ. The results provide evidence for the potential role of QSYQ in treating myocardial fibrosis following I/R injury. This effect may be associated with QSYQ's inhibition effect on monocyte chemotaxis and TGFß1/Smads signaling pathway with different component targeting distinct link (s) of the signaling.