Sirtuin 5 alleviates apoptosis and autophagy stimulated by ammonium chloride in bovine mammary epithelial cells.

Ammonia (NH3) is an irritating and harmful gas that affects cell apoptosis and autophagy. Sirtuin 5 (SIRT5) has multiple enzymatic activities and regulates NH3-induced autophagy in tumor cells. In order to determine whether SIRT5 regulates NH3-induced bovine mammary epithelial cell apoptosis and autophagy, cells with SIRT5 overexpression or knockdown were generated and in addition, bovine mammary epithelial cells were treated with SIRT5 inhibitors. The results showed that SIRT5 overexpression reduced the content of NH3 and glutamate in cells by inhibiting glutaminase activity in glutamine metabolism, and reduced the ratio of ADP/ATP. The results in the SIRT5 knockdown and inhibitor groups were comparable, including increased content of NH3 and glutamate in cells by activating glutaminase activity, and an elevated ratio of ADP/ATP. It was further confirmed that SIRT5 inhibited the apoptosis and autophagy of bovine mammary epithelial cells through reverse transcription-quantitative PCR, western blot, flow cytometry with Annexin V FITC/PI staining and transmission electron microscopy. In addition, it was also found that the addition of LY294002 or Rapamycin inhibited the PI3K/Akt or mTOR kinase signal, decreasing the apoptosis and autophagy activities of bovine mammary epithelial cells induced by SIRT5-inhibited NH3. In summary, the PI3K/Akt/mTOR signal involved in NH3-induced cell autophagy and apoptosis relies on the regulation of SIRT5. This study provides a new theory for the use of NH3 to regulate bovine mammary epithelial cell apoptosis and autophagy, and provides guidance for improving the health and production performance of dairy cows.

PD-1 blockade enhances the effect of targeted chemotherapy on locally advanced pMMR/MSS colorectal cancer.

BACKGROUND: Patients with DNA mismatch repair-proficient/microsatellite stable (pMMR/MSS) colorectal cancer (CRC), which accounts for 85% of all CRC cases, display a poor respond to immune checkpoint inhibitors (i.e., anti-PD-1 antibodies). pMMR/MSS CRC patients with locally advanced cancers need effective combined therapies. METHODS: In this pilot study, we administered six preoperative doses of each 2-week cycle of the anti-PD-1 antibody sintilimab (at a fixed dose of 200 mg), oxaliplatin, and 5-FU/CF (mFOLFOX6) combined with five doses of bevacizumab (the number of doses was reduced to prevent surgical delays) to patients with cT4NxM0 colon or upper rectal cancers. And radical surgery was performed approximately 2 weeks after the last dose of neoadjuvant therapy. The primary endpoint was a pathologic complete response (pCR). We also evaluated major pathologic response (MPR, ≤10% residual viable tumor), radiological and pathological regression, safety, and tumor mutation burden (TMB), and tumor microenvironment (TME) characteristics. RESULTS: By the cutoff date (September 2023), 22 patients with cT4NxM0 pMMR/MSS colon or upper rectal cancers were enrolled and the median follow-up was 24.7 months (IQR: 21.1-26.1). All patients underwent R0 surgical resection without treatment-related surgical delays. pCR occurred in 12 of 22 resected tumors (54.5%) and MPR occurred in 18 of 22 (81.8%) patients. At the cutoff date, all patients were alive, and 21/22 were recurrence-free. Treatment-related adverse events of grade 3 or higher occurred in of 2/22 (9.1%) patients. Among the pCR tumors, two were found to harbor POLE mutations. The degree of pathological regression was significantly greater than that of radiological regression (p = 1.35 × 10-8). The number of CD3+/CD4+ cells in the tumor and stroma in pretreated biopsied tissues was markedly lower in pCR tumors than in non-pCR tumors (p = 0.038 and p = 0.015, respectively). CONCLUSIONS: Neoadjuvant sintilimab combined with bevacizumab and mFOLFOX6 was associated with few side effects, did not delay surgery, and led to pCR and non-pCR in 54.5% and 81.8% of the cases, respectively. Downregulation of CD3/CD4 expression in the tumor and stroma is related to pCR. However, the molecular mechanisms underlying PD-1 blockade-enhanced targeted chemotherapy require further investigation.

Controllable non-uniformly distributed spiking cluster generation in broadband optoelectronic oscillator.

An approach to achieve controllable non-uniformly distributed spiking cluster generation is proposed and demonstrated based on an externally-triggered broadband optoelectronic oscillator (OEO). The theory of controlling the distribution of the spiking pulses in a spiking cluster is established. Based on the theory, the dynamic and the distribution characteristics are analyzed and revealed in the stable spiking oscillation state under different externally-injected trigger signal voltages. The peak-voltage envelop of the cluster and the interval of the spiking pulses are demonstrated to have an approximate negative linearity relationship with the externally-injected trigger signal voltage in both the numerical simulation and the experiment, where a square waveform, a trapezoidal waveform, a parabola waveform, and a half-sinusoidal waveform are used as the externally-injected trigger signals. The results indicate that the spiking pulse distribution in the generated spiking cluster can be well controlled through tuning the externally-injected trigger signal voltage. The proposed scheme can be utilized in spiking encoding and reservoir computing.

Phase-locked dual-frequency microwave signal generation in an optoelectronic oscillator based on frequency mixing mutual injection.

An approach to generating stable phase-locked dual-frequency microwave signals is proposed and demonstrated based on a dual-passband optoelectronic oscillator (OEO). Mode gain competition is broken by employing frequency mixing mutual injection effect to realize phase locking between the two oscillation signals, which is achieved by applying a single-tone signal to a microwave mixer in the OEO cavity. In addition, a dual-loop configuration with balanced detection is utilized to ensure a high side mode suppression ratio (SMSR) and ultra-low phase noise, which also enhances the stability of the generated signal. In the experiment, a phase-locked dual-frequency microwave signal at 9.9982 GHz and 10.1155 GHz is generated by using the proposed OEO scheme. The SMSR and the phase noise are 75 dB and -141 dBc/Hz@10 kHz, respectively. Additionally, the Allan deviation of the generated signal is in the order of 10-11@1 s. These parameters are superior to those based on the same OEO but with a single-loop configuration, which are also compared in detail.

A consensus genome of sika deer (Cervus nippon) and transcriptome analysis provided novel insights on the regulation mechanism of transcript factor in antler development.

BACKGROUND: Sika deer (Cervus nippon) holds significance among cervids, with three genomes recently published. However, these genomes still contain hundreds of gaps and display significant discrepancies in continuity and accuracy. This poses challenges to functional genomics research and the selection of an appropriate reference genome. Thus, obtaining a high-quality reference genome is imperative to delve into functional genomics effectively. FINDINGS: Here we report a high-quality consensus genome of male sika deer. All 34 chromosomes are assembled into single-contig pseudomolecules without any gaps, which is the most complete assembly. The genome size is 2.7G with 23,284 protein-coding genes. Comparative genomics analysis found that the genomes of sika deer and red deer are highly conserved, an approximately 2.4G collinear regions with up to 99% sequence similarity. Meanwhile, we observed the fusion of red deer's Chr23 and Chr4 during evolution, forming sika deer's Chr1. Additionally, we identified 607 transcription factors (TFs) that are involved in the regulation of antler development, including RUNX2, SOX6, SOX8, SOX9, PAX8, SIX2, SIX4, SIX6, SPI1, NFAC1, KLHL8, ZN710, JDP2, and TWST2, based on this consensus reference genome. CONCLUSIONS: Our results indicated that we acquired a high-quality consensus reference genome. That provided valuable resources for understanding functional genomics. In addition, discovered the genetic basis of sika-red hybrid fertility and identified 607 significant TFs that impact antler development.

Novel intelligent packaging films based on starch/PVA with Cu-ICA nanocrystal as functional compatibilizer for monitoring food freshness.

Considering public health and environmental safety, the development of reliable and efficient monitoring methods is essential to ensure food quality and safety. Herein, a new Cu-based metal organic framework (Cu-ICA) nanocrystal with ammonia-sensitive performance was built up and then introduced as a functional compatibilizer of starch/polyvinyl alcohol (STA/PVA) blend to develop high-performance intelligent packaging films for food freshness monitoring. The introduction of Cu-ICA upgraded the compatibility, mechanical strength (42.9 MPa), UV-protection (with UV transmittance of only 2.8 %), and moisture/oxygen barrier performances of STA/PVA film. Furthermore, the developed STA/PVA/Cu-ICA films presented long-term colour stability, outstanding antibacterial efficacy (over 99.5 %) toward both Escherichia coli and Staphylococcus aureus bacteria, as well as remarkable ammonia-sensitive discoloration capability. The STA/PVA/Cu-ICA films possessed visually identifiable colour change during the monitoring of shrimp spoilage. These findings indicate that the developed STA/PVA/Cu-ICA film possesses tremendous potential as an intelligent active packaging material.

High-performance carboxymethyl starch/PVA based intelligent packaging films engineered with Cu-Trp nanocrystal as functional compatibilizer.

A spindle-like Cu-based framework (Cu-Trp, Trp = L-Tryptophan) nanocrystal with ammonia-responsiveness was fabricated via simple aqueous solution approach, and it was subsequently explored as a functional compatibilizer of carboxymethyl starch/polyvinyl alcohol (CMS/PVA) blend toward constructing high-performance intelligent packaging films. The results showed that incorporation of Cu-Trp nanocrystal into CMS/PVA blend resulted in significant promotions regarding to the compatibility, mechanical strength (42.92 MPa), UV-blocking (with UV transmittance of only 2.4%), and water vapor barrier effectiveness of the blend film. Besides, the constructed CMS/PVA/Cu-Trp nanocomposite film exhibited superb long-term color stability, favorable antibacterial capacity (over 98.0%) toward both E. coli and S. aureus bacteria, as well as color change ability under ammonia environment. Importantly, the application trial confirmed that the CMS/PVA/Cu-Trp nanocomposite film is capable of visually monitoring shrimp spoilage during storage. These results implied that the CMS/PVA/Cu-Trp nanocomposite film holds tremendous potential as an intelligent active packaging material.

Prevalence and influencing factors of malnutrition in stroke patients with bulbar paralysis: a cross-sectional study in China.

Background: Although malnutrition has been shown to influence the clinical outcomes of Stroke Patients with Bulbar Paralysis (SPBP), the prevalence and influencing factors have yet to be uncovered. Objective: This study aims to assess the current prevalence and factors associated with malnutrition in SPBP. Methods: A multicenter cross-sectional investigation was conducted among SPBP in China from 2019 to 2021. Information was collected on basic information, health condition, diagnosis, treatment, neurological function, activities of daily living, swallowing function, and nutritional status. A multivariable logistic regression model was used to identify the factors that influenced nutritional status. ROC analysis was used to assess the predictive value of each independent influencing factor and the logit model. Results: In total, 774 SPBP were enrolled, and the prevalence of malnutrition was 60.59%. Pulmonary infection [aOR:2.849, 95%CI: (1.426, 5.691)], hemoglobin [aOR: 0.932, 95%CI: (0.875, 0.982)], serum albumin [aOR: 0.904, 95%CI: (0.871, 0.938)], total protein [aOR: 0.891, 95%CI: (0.819, 0.969)], prealbumin [aOR: 0.962, 95%CI: (0.932, 0.993)], and National Institute of Health Stroke Scale (NIHSS) scores [aOR: 1.228, 95%CI: (1.054, 1.431)] were independent factors associated with malnutrition in SPBP. ROC analysis revealed that the logit model had the best predictive value [area under the curve: 0.874, 95% CI: (0.812, 0.936); specificity: 83.4%; sensitivity: 79.3%; p < 0.05]. Subgroup analysis showed that the nutritional status in dysphagic SPBP was additionally influenced by swallowing function and nutrition support mode. Conclusion: The prevalence of malnutrition in SPBP was 60.59%. Pulmonary infection, hemoglobin level, and NIHSS score were the independent factors associated with malnutrition. Swallowing function and nutrition support mode were the factors associated with malnutrition in dysphagic SPBP.

Mechanism of ameliorating cerebral ischemia/reperfusion injury by antioxidant inhibition of autophagy based on network pharmacology and experimental verification.

Cerebral ischemia-reperfusion injury (CIRI) is one of the most difficult challenges in cerebrovascular disease research. It is primarily caused by excessive autophagy induced by oxidative stress. Previously, a novel compound X5 was found, and the excellent antioxidant activity of it was verified in this study. Moreover, network pharmacological analysis suggested that compound X5 was closely associated with autophagy and the mTOR pathway. In vitro, X5 could significantly inhibit the expression of autophagy proteins Beclin-1 and LC3-ß, which are induced by H2O2, and promote the expression of SIRT1. In vivo, compound X5 significantly reduced the infarct size and improved the neurological function scores in the middle cerebral artery occlusion (MCAO) model of rats. In conclusion, ROS-induced autophagy is closely related to mTOR, SIRT1 and others, and X5 holds promise as a candidate for the treatment of CIRI.

Gene replacement therapy in Bietti crystalline corneoretinal dystrophy: an open-label, single-arm, exploratory trial.

Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2, which results in blindness in the working-age population, and there is currently no available treatment. Here, we report the results of the first-in-human clinical trial (NCT04722107) of gene therapy for Bietti crystalline corneoretinal dystrophy, including 12 participants who were followed up for 180-365 days. This open-label, single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein (rAAV2/8-hCYP4V2). Participants received a single unilateral subretinal injection of 7.5 × 1010 vector genomes of rAAV2/8-hCYP4V2. Overall, 73 treatment-emergent adverse events were reported, with the majority (98.6%) being of mild or moderate intensity and considered to be procedure- or corticosteroid-related; no treatment-related serious adverse events or local/systemic immune toxicities were observed. Compared with that measured at baseline, 77.8% of the treated eyes showed improvement in best-corrected visual acuity (BCVA) on day 180, with a mean ± standard deviation increase of 9.0 ± 10.8 letters in the 9 eyes analyzed (p = 0.021). By day 365, 80% of the treated eyes showed an increase in BCVA, with a mean increase of 11.0 ± 10.6 letters in the 5 eyes assessed (p = 0.125). Importantly, the patients' improvement observed using multifocal electroretinogram, microperimetry, and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment. We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2 (named ZVS101e).

Efficient tunable cascaded Raman source with all-silica fibers based on 2-µm DSR pulse pumping.

We present an efficient tunable all-silica-fiber 2nd-order cascaded Raman pulse laser utilizing 2-µm dissipative-soliton-resonance (DSR) rectangular pulses for pumping and highly GeO2-doped silica fiber as Raman gain medium. When pumped at 1966.5 nm, the maximum 1st-order Raman optical conversion efficiency is up to 64.4% at 2153 nm, with 92.4% spectral purity and 0.39-W average power. The maximum 2nd-order Raman optical conversion efficiency is 19.3% at 2370 nm, with 39.2% spectral purity and 0.25-W average power. To our knowledge, these conversion efficiencies and spectral purities represent the highest levels achieved in a mid-infrared all-silica-fiber cascaded pulsed Raman laser. Additionally, by adjusting the central wavelength of the DSR seed pulse, the 2nd-order Raman light can be tuned within a range of 41 nm (2354∼2395 nm). Our system provides a simple and easy-to-implement solution for realizing efficient tunable cascaded pulsed Raman lasers in the 2.4-µm band.

Detoxifying bacterial genes for deoxynivalenol epimerization confer durable resistance to Fusarium head blight in wheat.

Fusarium head blight (FHB) and the presence of mycotoxin deoxynivalenol (DON) pose serious threats to wheat production and food safety worldwide. DON, as a virulence factor, is crucial for the spread of FHB pathogens on plants. However, germplasm resources that are naturally resistant to DON and DON-producing FHB pathogens are inadequate in plants. Here, detoxifying bacteria genes responsible for DON epimerization were used to enhance the resistance of wheat to mycotoxin DON and FHB pathogens. We characterized the complete pathway and molecular basis leading to the thorough detoxification of DON via epimerization through two sequential reactions in the detoxifying bacterium Devosia sp. D6-9. Epimerization efficiently eliminates the phytotoxicity of DON and neutralizes the effects of DON as a virulence factor. Notably, co-expressing of the genes encoding quinoprotein dehydrogenase (QDDH) for DON oxidation in the first reaction step, and aldo-keto reductase AKR13B2 for 3-keto-DON reduction in the second reaction step significantly reduced the accumulation of DON as virulence factor in wheat after the infection of pathogenic Fusarium, and accordingly conferred increased disease resistance to FHB by restricting the spread of pathogenic Fusarium in the transgenic plants. Stable and improved resistance was observed in greenhouse and field conditions over multiple generations. This successful approach presents a promising avenue for enhancing FHB resistance in crops and reducing mycotoxin contents in grains through detoxification of the virulence factor DON by exogenous resistance genes from microbes.

Effects of Internal Stress and Hydrogen Penetration on the Performance of Er2O3 Coatings as Hydrogen Permeation Barriers.

Ceramic coatings that can effectively prevent hydrogen permeation have a wide range of applications in hydrogen energy and nuclear fusion reactors. In this study, for the first time, the internal stress of Er2O3 coatings was found to be a key factor that could determine their hydrogen permeation resistance and lifespan. The internal stress was controlled by designing layered Er2O3 coatings. The internal stress increased with an increasing number of Er2O3 layers. When the number of layers was below 15, the increased internal stress did not adversely affect the coating performance and might help to increase its hydrogen permeation resistance. Although the overall thickness of the 15-layer Er2O3 coating was only 97 nm, its hydrogen permeation reduction factor (PRF) reached the highest value of 626, whereas a further increase in the internal stress detrimentally affected the ability of the coating to reduce hydrogen permeation. In addition, the experimental observations and simulation results revealed that the performance of the Er2O3 coatings was related to the hydrogen atoms that penetrated the coating, which weakened the Er-O bonds and consequently decreased the Er2O3 fracture limit. This study provides insights into the effects of internal stress and hydrogen penetration on the performance of ceramic coatings as hydrogen permeation barriers and will help guide strategies for the structure design of hydrogen permeation barriers possessing high PRFs and long lifespans.

Overexpression of TNFSF11 reduces GPX4 levels and increases sensitivity to ferroptosis inducers in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD), the most common and lethal subtype of lung cancer, continues to be a major health concern worldwide. Despite advances in targeted and immune therapies, only a minority of patients derive substantial benefits. As a result, the urgent need for novel therapeutic strategies to improve lung cancer treatment outcomes remains undiminished. METHODS: In our study, we employed the TIMER database to scrutinize TNFSF11 expression across various cancer types. We further examined the differential expression of TNFSF11 in normal and tumor tissues utilizing the TCGA-LUAD dataset and tissue microarray, and probed the associations between TNFSF11 expression and clinicopathological parameters within the TCGA-LUAD dataset. We used the GSE31210 dataset for external validation. To identify genes strongly linked to TNFSF11, we engaged LinkedOmics and conducted a KEGG pathway enrichment analysis using the WEB-based Gene SeT AnaLysis Toolkit. Moreover, we investigated the function of TNFSF11 through gene knockdown or overexpression approaches and explore its function in tumor cells. The therapeutic impact of ferroptosis inducers in tumors overexpressing TNFSF11 were also investigated through in vivo and in vitro experiments. Through these extensive analyses, we shed light on the potential role of TNFSF11 in lung adenocarcinoma, underscoring potential therapeutic targets for this malignancy. RESULTS: This research uncovers the overexpression of TNFSF11 in LUAD patients and its inverse correlation with peroxisome-related enzymes. By utilizing gene knockdown or overexpression assays, we found that TNFSF11 was negatively associated with GPX4. Furthermore, cells with TNFSF11 overexpression were relatively more sensitive to the ferroptosis inducers. CONCLUSIONS: Our research has provided valuable insights into the role of TNFSF11, revealing its negative regulation of GPX4, which could be influential in crafting therapeutic strategies. These findings set the stage for further exploration into the mechanisms underpinning the relationship between TNFSF11 and GPX4, potentially opening up new avenues for precision medicine in the treatment of LUAD.

Analysis of risk factors and development of predictive model for malnutrition in patients with traumatic brain injury.

Malnutrition is a highly prevalent complication in patients with traumatic brain injury (TBI), and it is closely related to the prognosis of patients. Accurate identification of patients at high risk of malnutrition is essential. Therefore, we analyzed the risk factors of malnutrition in patients with TBI and developed a model to predict the risk of malnutrition. A retrospective collection of 345 patients with TBI, and they were divided into malnutrition and comparison groups according to the occurrence of malnutrition. Univariate correlation and multifactor logistic regression analyses were performed to determine patients' malnutrition risk factors. We used univariate and logistic regression (forward stepwise method) analyses to identify significant predictors associated with malnutrition in patients with TBI and developed a predictive model for malnutrition prediction. The model's discrimination, calibration, and clinical utility were evaluated using the receiver operating characteristic (ROC) curve, calibration plots, and decision curve analysis (DCA). A total of 216 patients (62.6%) developed malnutrition. Multifactorial logistic regression analysis showed that pulmonary infection, urinary tract infection, dysphagia, application of NGT, GCS score ≤ 8, and low ADL score were independent risk factors for malnutrition in patients with TBI (P < 0.05). The area under the curve of the model was 0.947. Calibration plots showed good discrimination of model calibration. DCA showed that the column line plot models were all clinically meaningful when nutritional interventions were performed over a considerable range of threshold probabilities (0-0.98). Malnutrition is widespread in patients with TBI, and the nomogram is a good predictor of whether patients develop malnutrition.

How stroke-related dysphagia relates to quality of life: the mediating role of nutritional status and psychological disorders, and the moderating effect of enteral nutrition mode.

Background: Although stroke-related dysphagia has been shown to influence quality of life (QOL), the underlying mechanisms have yet to be uncovered. Objective: This study aims to investigate the mediating role of nutritional status and psychological disorders in the relationship between stroke-related dysphagia and QOL in stroke patients and explore the moderating effect of enteral nutrition mode. Methods: In 2022, A questionnaire survey using stratified random sampling was conducted on 5,322 stroke patients with dysphagia, including Functional Oral Intake Scale (FOIS), Swallowing Quality of Life Questionnaire, Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7) to assess dysphagia, QOL and psychological disorders, respectively, for each participant. Records of serum albumin, Hemoglobin, Total serum protein, serum prealbumin and Body mass index were enrolled to assess nutritional status. Results: FOIS demonstrated a significant positive predictive effect on QOL. Nutritional status and psychological disorders (PHQ-9 and GAD-7) mediated the relationship between FOIS and QOL. Nutritional status-psychological disorders showed a chain mediation effect in the relationship between FOIS and QOL. The moderating effect of enteral nutrition mode was observed. Conclusion: The mediating role of nutritional status and psychological disorders with moderating effect of enteral nutrition mode in the relationship between dysphagia and QOL in stroke patients was found.

Effect of Intermittent Oro-Esophageal Tube Feeding in Bulbar Palsy After Ischemic Stroke: A Randomized Controlled Study.

BACKGROUND: Nasogastric tube feeding (NG) has been widely used in patients with bulbar palsy after ischemic stroke but is associated with a significant risk of complications including malnutrition and pneumonia. Intermittent oro-esophageal tube feeding (IOE) can help alleviate these concerns. This study explored the clinical effect of IOE versus NG on nutritional status, swallowing function, stroke-associated pneumonia, and depression in patients with bulbar palsy after ischemic stroke. METHODS: This randomized controlled study included 148 patients with bulbar palsy after ischemic stroke who underwent routine treatment and swallowing rehabilitation training in the Department of Rehabilitation Medicine between July 2017 and July 2019 in China. The participants were randomly divided into the IOE group (n=74) and NG group (n=74) with IOE and NG as nutritional supports, respectively. The primary outcome was nutritional status including (1) body mass index (kg/m2), (2) serum ALB (albumin, g/L), and (3) PA (prealbumin, mg/L). The secondary outcomes were (1) swallowing function including (i) Functional Oral Intake Scale (FOIS) and (ii) Penetration-Aspiration Scale, (2) pneumonia, (3) depression, and (4) adverse events. Statistical analyses for continuous outcomes were performed using t test, Mann-Whitney U test and Wilcoxon signed-rank test and categorical variables using χ2 test. SPSS 21.0 was used for all analysis. RESULTS: There were no significant baseline differences between the 2 groups. After the treatment, the IOE group demonstrated significantly better results compared with the NG group in ALB ([32.71±0.94] versus [32.28±0.81] g/L; P=0.003), PA ([278.15±13.81] versus [270.31±15.08] mg/L; P=0.001], body mass index ([19.77±1.03] versus [19.41±0.98] kg/m2; P=0.002], FOIS (P<0.001), Penetration-Aspiration Scale (P<0.001), stroke-associated pneumonia ([1, 4.05%] versus [26, 35.14%]; P<0.001), depression ([1, 1.35%] versus [44, 59.46%]; P<0.001) and overall less adverse events (reflux, fever, discomfort in the throat; P<0.001). CONCLUSIONS: In patients with dysphagia with bulbar palsy after ischemic stroke who received routine treatment and swallowing rehabilitation training, IOE is safer and more conducive to the improvement of nutritional status, swallowing function, stroke-associated pneumonia, and depression than NG. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR-INC-17011741.

A Enhanced Fluorescent Probe for Simultaneous Detection and Discrimination of Hydrogen Bisulfite Anions and Glutathione.

Bisulfite (HSO3-) and biological thiols molecules, such as glutathione (GSH), cysteine (Cys), and homocysteine (Hcy), play important roles in organisms. Developing a fluorescent probe that can simultaneously detect and distinguish HSO3- and biological thiols is of great significance. In this study, ethyl(2E,4Z)-5-chloro-2-cyano-5-(7-(diethylamino)-2-oxo-2 H-chromen-3-yl)penta-2,4-dienoate (CCO) as a novel enhanced fluorescence probe was synthesized by integrating coumarin derivatives and ethyl cyanoacetate, which can simultaneous detection and discrimination of hydrogen bisulfite anions and glutathione. The sensing mechanism was elucidated through spectral analysis and some control experiments. In weakly alkaline environments, the probe not only has good selectivity for HSO3- and GSH, but also has a lower detection limits of 0.0179 µM and 0.2034 µM. The probe exhibited fuorescent turn-on for distinguishing with 296 and 28 fold the fluorescent intensity increase at 486 and 505 nm, respectively, through diferent excitation wavelengths. This provides a new method for simultaneous detection and discrimination of HSO3- and biological thiol cell levels and further applications.

The spatio-temporal expression analysis of parathyroid hormone like hormone gene provides a new insight for bone growth of the antler tip tissue in sika deer.

OBJECTIVE: Parathyroid hormone like hormone (PTHLH), as an essential factor for bone growth, is involved in a variety of physiological processes. The aim of this study was to explore the role of PTHLH gene in the growth of antlers. METHODS: The coding sequence (CDS) of PTHLH gene cDNA was obtained by cloning in sika deer (Cervus nippon), and the bioinformatics was analyzed. The quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the differences expression of PTHLH mRNA in different tissues of the antler tip at different growth periods (early period, EP; middle period, MP; late period, LP). RESULTS: The CDS of PTHLH gene was 534 bp in length and encoded 177 amino acids. Predictive analysis results revealed that the PTHLH protein was a hydrophilic protein without transmembrane structure, with its secondary structure consisting mainly of random coil. The PTHLH protein of sika deer had the identity of 98.31%, 96.82%, 96.05%, and 94.92% with Cervus canadensis, Bos mutus, Oryx dammah and Budorcas taxicolor, which were highly conserved among the artiodactyls. The qRT-PCR results showed that PTHLH mRNA had a unique spatio-temporal expression pattern in antlers. In the dermis, precartilage, and cartilage tissues, the expression of PTHLH mRNA was extremely significantly higher in MP than in EP, LP (p<0.01). In the mesenchyme tissue, the expression of PTHLH mRNA in MP was significantly higher than that of EP (p<0.05), but extremely significantly lower than that of LP (p<0.01). The expression of PTHLH mRNA in antler tip tissues at all growth periods had approximately the same trend, that is, from distal to basal, it was first downregulated from the dermis to the mesenchyme and then continuously up-regulated to the cartilage tissue. CONCLUSION: PTHLH gene may promote the rapid growth of antler mainly through its extensive regulatory effect on the antler tip tissue.

Successful immunotherapy with PD-1 Iinhibitor for advanced pancreatic cancer: report of two cases and review of literature.

Pancreatic cancer is a highly malignant tumor, and most patients are diagnosed at an advanced stage. Unfortunately, due to the immunosuppressive tumor microenvironment of pancreatic cancer, the benefits of immunotherapy for patients with advanced pancreatic cancer are still unclear. Here, we present two cases of advanced pancreatic cancer being controlled by immunotherapy, with pathological diagnoses of ductal adenocarcinoma and acinar cell carcinoma, respectively. Next-generation sequencing (NGS) of both patients is high tumor mutation burden (tumor mutation burden-High) and microsatellite stable. The patient with pancreatic ductal adenocarcinoma was diagnosed as a locally advanced disease (stage III). She received irreversible electroporation, used the programmed death receptor-1 (PD-1) inhibitor (pembrolizumab) combined with chemotherapy (S-1), and then used only the PD-1 inhibitor as a maintenance treatment. As a result, the patient's lesion was significantly reduced, with a partial response time of up to 31 months. The patient with acinar cell carcinoma was diagnosed as a metastatic disease (stage IV), next-generation sequencing revealed mutations in SMAD4 and KMT2D, and two chemotherapy regimens were used unsuccessfully. Then, the combination of chemotherapy with PD-1 (tislelizumab) and vascular endothelial growth factor/vascular endothelial growth factor receptor (anlotinib) inhibitors were used, and the lesions of the patient were significantly reduced, and the progression-free survival after immunotherapy was 19 months. In advanced pancreatic cancer, a prognosis of this magnitude is rare. Our cases reveal the potential of immunotherapy as a cornerstone treatment in the management of advanced pancreatic cancer.