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Abstract Myocardial infarction (MI) is one of the leading causes of death. This is attributed to the dramatic changes in the myocardial microenvironment post-MI. Therefore, effective intervention in the early stages of MI is significant for inhibiting its progression and improving cardiac function. Herein, an injectable composite hydrogel scaffold (Gel-pBP@Mg) was developed by integrating magnesium (Mg)-modified black phosphorus nanosheets (pBP@Mg) into a reactive oxygen species-responsive hydrogel (Gel). This loose and porous Gel provides a natural platform for carrying pBP@Mg. In situ, sustained release of pBP@Mg is achieved via responsive ROS degradation in the infarct site. The high ROS reactivity of Black phosphorus nanosheets (BPNSs) can effectively inhibit the progression of oxidative stress in the infarct area and reduce inflammatory response by down-regulating the NF-κB pathway. Additionally, the sustained release of Mg loaded on the surface of BPNSs can effectively promote angiogenesis in MI, which is significant for the long-term prognosis after infarction. Our developed Gel-pBP@Mg effectively blocked infarction progression and improved myocardial function by sustainably inhibiting the “oxidative stress-inflammation” reaction chain and pro-angiogenesis. This study reveals Gel-pBP@Mg composite therapeutic potential in treating MI through In vitro and In vivo studies, providing a promising modality for MI treatment. Graphical abstract

BackgroundPressure support ventilation (PSV) is one of the most frequently used ventilator modes in the intensive care unit (ICU). The successful implementation of PSV depends on matching the patient’s inspiratory effort with the ventilator support. In clinical practice, the pressure support level is usually set and adjusted according to tidal volume and respiratory rate. However, these parameters may not fully represent the patient’s effort. Previous studies have shown that pressure muscle index (PMI), which is measured as the difference between the peak and plateau airway pressure during an end-inspiratory airway occlusion, could reliably determine the low and high inspiratory effort during PSV. Herein we present the study protocol for the Inspiratory effort-Targeted Pressure Support Ventilation (IT-PSV) trial to determine the effect of a PMI-targeted pressure support setting strategy on clinical outcomes in patients undergoing PSV.Methods and analysisThis is a cluster randomized controlled trial. Sixteen ICUs in academic hospitals will be included, eight of which will be randomly allocated to the PMI-targeted group and eight to the tidal volume/respiratory rate-targeted group. Before the initiation of the study, a four-week comprehensive training program, which includes courses of PSV initiation, pressure support adjustment, and weaning process, will be conducted for all staff in the participating ICUs. Adult patients with acute hypoxic respiratory failure and undergoing PSV within 24 h will be included. Pressure support setting and adjustment will follow the strategy according to the grouping. The primary outcome is the ventilator-free days at 28 days after enrollment. The patients will be followed up until successful weaning or separation of mechanical ventilation, death, hospital discharge, or until 28 days after randomization, whichever comes first.DiscussionThe IT-PSV trial will examine the effect of an inspiratory effort-targeted PSV setting strategy on the duration of mechanical ventilation. If positive, it will provide a new physiological-based PSV management that could potentially facilitate protective assisted ventilation.Clinical trial registrationClinicalTrials.gov, identifier NCT06526598.

Background: Generalized pustular psoriasis (GPP) is a rare skin disease characterized by episodes of widespread sterile pustules. Methods: A retrospective cohort study using data from the US IBM MarketScan Commercial and Optum Clinformatics Data Mart databases between October 1, 2015 and March 31, 2020 was performed to describe adherence and persistence to biologics in patients with GPP. Patients were aged ≥18 years with newly diagnosed GPP (International Classification of Diseases code L40.1) and had ≥1 inpatient or ≥2 outpatient claims. Results: Biologics were dispensed to 110 of 502 (22%) and 73 of 528 (14%) patients from MarketScan and Optum databases, respectively. The mean proportion of days covered (PDC) (range) was similar in both databases (MarketScan, 65% [8%-100%]; Optum, 59% [8%-99%]), and good adherence (≥80% PDC) was uncommon (MarketScan, 36%; Optum, 24%). Mean (standard deviation) persistence was similar in both databases (MarketScan, 287 [122] days; Optum, 261 [134] days). In Optum, the mean PDC was similar between age categories; good adherence was more common in patients aged 18 to 64 years (28%) versus ≥65 years (13%). Mean persistence was longer in patients aged 18 to 64 years (267 days) versus ≥65 years (242 days). Conclusions: Overall, adherence and persistence were generally poor and varied according to the biologic class, database, and age. Improving adherence may help improve GPP treatment outcomes.

Pulmonary hypertension (PH) is a fatal disorder characterized by pulmonary vascular remodeling and obstruction. The phosphodiesterase 4 (PDE4) family hydrolyzes cyclic AMP (cAMP) and is comprised of four subtypes (PDE4A–D). Previous studies have shown the beneficial effects of pan-PDE4 inhibitors in rodent PH; however, this class of drugs is associated with side effects owing to the broad inhibition of all four PDE4 isozymes. Here, we demonstrate that PDE4B is the predominant PDE isozyme in lungs and that it was upregulated in rodent and human PH lung tissues. We also confirmed that PDE4B is mainly expressed in the lung endothelial cells (ECs). Evaluation of PH in Pde4b wild type and knockout mice confirmed that Pde4b is important for the vascular remodeling associated with PH. In vivo EC lineage tracing demonstrated that Pde4b induces PH development by driving endothelial-to-mesenchymal transition (EndMT), and mechanistic studies showed that Pde4b regulates EndMT by antagonizing the cAMP-dependent PKA–CREB–BMPRII axis. Finally, treating PH rats with a PDE4B-specific inhibitor validated that PDE4B inhibition has a significant pharmacological effect in the alleviation of PH. Collectively, our findings indicate a critical role for PDE4B in EndMT and PH, prompting further studies of PDE4B-specific inhibitors as a therapeutic strategy for PH.

In a displacement ventilation system, the human body heat source plays a significant role and should not be overlooked. The intensity of human activity is a crucial factor in determining the amount of heat generated by the human body. In this work, the impact of thermal plumes generated by different levels of human activity intensity on the temperature stratification and ventilation efficiency in displacement ventilation system have been explored with experimental and numerical methods. The airflow patterns in the displacement air supply system under various levels of human activity intensity were simulated. The results show that under the same air supply speed, as the human activity intensity increasing from 125 W to 402 W, the phenomenon of temperature stratification becomes more pronounced. With the promotion of thermal plumes, the air flow velocity on the human body surface increases, leading to an enhancement in ventilation efficiency. Therefore, to elimination of the indoor thermal load, the air supply speed can be reasonably reduced according to the human activity intensity in the room, further enhancing the energy-saving effect of displacement ventilation.

Introduction Although pressure support ventilation is one of the most commonly used assisted ventilation modes in intensive care units, there is still a lack of precise strategies for setting pressure support. By performing an end-inspiratory airway occlusion, the difference between the peak and plateau airway pressure, which is defined as pressure muscle index (PMI), can be easily measured on the ventilator screen. Previous studies have shown that PMI is accurate in detecting high and low inspiratory effort. No study has been conducted to investigate the use of PMI as an indicator for setting inspiratory pressure support.Method and analysis This is a study protocol for a prospective, single-centre, randomised controlled, pilot trial. Sixty participants undergoing pressure support ventilation will be randomly assigned in a 1:1 ratio to the control group or intervention group, with pressure support adjusted according to standard care or guided by the PMI strategy for 48 hours, respectively. The feasibility of the PMI-guided strategy will be evaluated. The primary endpoint is the proportion of inspiratory effort measurements within a well-accepted ‘normal’ range, which is predefined as oesophageal pressure–time product per minute between 50 and 200 cmH2O⋅s/min, for each patient during 48 hours of pressure support adjustment.Ethics and dissemination The study protocol has been approved by Beijing Tiantan Hospital (KY2023-005-02). The data generated in the present study will be available from the corresponding author on reasonable request. The results of the trial will be submitted to international peer-reviewed journals.Trial registration number NCT05963737; ClinicalTrials.org.

Elastic moduli, e.g. shear modulus G and bulk modulus K, are important parameters of geotechnical materials, which are not only the indices for the evaluation of the deformation ability of soils but also the important basic parameters for the development of the constitutive models of geotechnical materials. In this study, a series of triaxial loading-unloading-reloading shear tests and isotropic loading-unloading-reloading tests are conducted to study several typical mechanical properties of coral calcareous sand (CCS), and the void ratio evolution during loading, unloading and reloading. The test results show that the stress-strain curves during multiple unloading processes are almost parallel, and their slopes are much greater than the deformation modulus at the initial stage of loading. The relationship between the confining pressure and the volumetric strain can be defined approximately by a hyperbolic equation under the condition of monotonic loading of confining pressure. Under the condition of confining pressure unloading, the evolution of void ratio is linear in the e-lnp′ plane, and these lines are a series of almost parallel lines if there are multiple processes of unloading. Based on the experimental results, it is found that the modified Hardin formulae for the elastic modulus estimation have a significant deviation from the tested values for CCS. Based on the experimental results, it is proposed that the elastic modulus of soils should be determined by the intersection line of two spatial surfaces in the G/K-e-p'/pa space (pa: atmosphere pressure). “Ye formulation” is further proposed for the estimation of the elastic modulus of CCS. This new estimation formulation for soil elastic modulus would provide a new method to accurately describe the mechanical behavior of granular soils.

It is inevitable for polyphenols and polysaccharides to interact during food preparation. Modifications in microstructure can lead to changes in the physical and chemical properties of food systems, which in turn may influence the nutritional characteristics and functional activities of the food. Recent studies have shown that, in addition to traditional Chinese medicine compounds, certain natural polysaccharides and polyphenols exhibit significant anti-inflammatory and antioxidant properties. These compounds are also associated with beneficial therapeutic effects for the prevention and treatment of acute lung injury. The objective of this study was to examine the synergistic antioxidant effects of chlorogenic acid (CA) and Lycium barbarum polysaccharide (LBP) in various ratios, along with their combined antioxidant and anti-inflammatory effects on LPS-induced inflammation in rat alveolar macrophages. Using the Combination Index (CI), which quantifies the synergistic or antagonistic effect of two substances, all four combinations showed synergistic antioxidant properties over a range of concentrations by in vitro antioxidant property experiments. However, based on comparing them, the four group ratios exhibited the highest antioxidant activity of the infusion at CA:LBP = 1:7, indicating synergistic interactions (CI < 1). In addition, the antioxidant and anti-inflammatory effects of the CA-LBP complex were observed to alleviate cellular inflammatory injury by reducing LPS-induced nitric oxide and reactive oxygen species production and inhibiting the release of inflammatory factors such as TNF-α and IL-6.

BackgroundThe successful implementation of assisted ventilation depends on matching the patient’s effort with the ventilator support. Pressure muscle index (PMI), an airway pressure based measurement, has been used as noninvasive monitoring to assess the patient’s inspiratory effort. The authors aimed to evaluate the feasibility of pressure support adjustment according to the PMI target and the diagnostic performance of PMI to predict the contribution of the patient’s effort during ventilator support.MethodsIn this prospective physiological study, 22 adult patients undergoing pressure support ventilation were enrolled. After an end-inspiratory airway occlusion, airway pressure reached a plateau, and the magnitude of change in plateau from peak airway pressure was defined as PMI. Pressure support was adjusted to obtain the PMI which was closest to −1, 0, +1, +2, and + 3 cm H2O. Each pressure support level was maintained for 20 min. Esophageal pressure was monitored. Pressure–time products of respiratory muscle and ventilator insufflation were measured, and the fraction of pressure generated by the patient was calculated to represent the contribution of the patient’s inspiratory effort.ResultsA total of 105 datasets were collected at different PMI-targeted pressure support levels. The differences in PMI between the target and the obtained value were all within ±1 cm H2O. As targeted PMI increased, pressure support settings decreased significantly from a median (interquartile range) of 11 (10–12) to 5 (4–6) cm H2O (p

Abstract Background Assessment of the patient’s respiratory effort is essential during assisted ventilation. We aimed to evaluate the accuracy of airway pressure (P aw)-based indices to detect potential injurious inspiratory effort during pressure support (PS) ventilation. Methods In this prospective diagnostic accuracy study conducted in four ICUs in two academic hospitals, 28 adult acute respiratory failure patients undergoing PS ventilation were enrolled. A downward PS titration was conducted from 20 cmH2O to 2 cmH2O at a 2 cmH2O interval. By performing an end-expiratory airway occlusion maneuver, the negative P aw generated during the first 100 ms (P 0.1) and the maximal negative swing of P aw (∆P occ) were measured. After an end-inspiratory airway occlusion, P aw reached a plateau, and the magnitude of change in plateau from peak P aw was measured as pressure muscle index (PMI). Esophageal pressure was monitored and inspiratory muscle pressure (P mus) and P mus–time product per minute (PTPmus/min) were used as the reference standard for the patient’s effort. High and low effort was defined as P mus > 10 and 200 and

Abstract Background Harnessing hepatocytes for basic research and regenerative medicine demands a complete understanding of the genetic determinants underlying hepatocyte differentiation and maturation. Single-cell CRISPR screens in organoids could link genetic perturbations with parallel transcriptomic readout in single cells, providing a powerful method to delineate roles of cell fate regulators. However, a big challenge for identifying key regulators during data analysis is the low expression levels of transcription factors (TFs), which are difficult to accurately estimate due to noise and dropouts in single-cell sequencing. Also, it is often the changes in TF activities in the transcriptional cascade rather than the expression levels of TFs that are relevant to the cell fate transition. Results Here, we develop Organoid-based Single-cell CRISPR screening Analyzed with Regulons (OSCAR), a framework using regulon activities as readouts to dissect gene knockout effects in organoids. In adult-stem-cell-derived liver organoids, we map transcriptomes in 80,576 cells upon 246 perturbations associated with transcriptional regulation of hepatocyte formation. Using OSCAR, we identify known and novel positive and negative regulators, among which Fos and Ubr5 are the top-ranked ones. Further single-gene loss-of-function assays demonstrate that Fos depletion in mouse and human liver organoids promote hepatocyte differentiation by specific upregulation of liver metabolic genes and pathways, and conditional knockout of Ubr5 in mouse liver delays hepatocyte maturation. Conclusions Altogether, we provide a framework to explore lineage specifiers in a rapid and systematic manner, and identify hepatocyte determinators with potential clinical applications.

Abstract The premetastatic niches (PMN) formed by primary tumor‐derived molecules regulate distant organs and tissues to further favor tumor colonization. Targeted PMN therapy may prevent tumor metastasis in the early stages, which is becoming increasingly important. At present, there is a lack of in‐depth understanding of the cellular and molecular characteristics of the PMN. Here, we summarize current research advances on the cellular and molecular characteristics of the PMN. We emphasize that PMN intervention is a potential therapeutic strategy for early prevention of tumor metastasis, which provides a promising basis for future research and clinical application.

Optimal spacing for vertical wells can be effectively predicted with several published methods, but methods suitable for assessing the proper horizontal well spacing are rare. This work proposes a method for calculating the optimal horizontal well spacing for an ultra-low permeability reservoir – the Yongjin reservoir in the Juggar Basin, northwestern China. The result shows that a spacing of 640 m is the most economical for the development of the reservoir. To better develop the reservoir, simulation approaches are used and a new model is built based on the calculated well spacing. Since the reservoir has an ultra-low permeability, gas injection is regarded as the preferred enhanced oil recovery (EOR) method. Injection of different gases including carbon dioxide, methane, nitrogen and mixed gas are modelled. The results show that carbon dioxide injection is the most efficient and economical for the development of the reservoir. However, if the reservoir produces enough methane, reinjecting methane is even better than injecting carbon dioxide.

Abstract Background New therapeutic targets are needed to improve the outcomes for gastric cancer (GC) patients with advanced disease. Evasion of programmed cell death (apoptosis) is a hallmark of cancer cells and direct induction of apoptosis by targeting the pro‐survival BCL2 family proteins represents a promising therapeutic strategy for cancer treatment. Therefore, understanding the molecular mechanisms underpinning cancer cell survival could provide a molecular basis for potential therapeutic interventions. Method Here we explored the role of BCL2L1 and the encoded anti‐apoptotic BCL‐XL in GC. Using Droplet Digital PCR (ddPCR) technology to investigate the DNA amplification of BCL2L1 in GC samples and GC cell lines, the sensitivity of GC cell lines to selective BCL‐XL inhibitors A1155463 and A1331852, pan‐inhibitor ABT‐263, and VHL‐based PROTAC‐BCL‐XL was analyzed using (CellTiter‐Glo) CTG assay in vitro. Western Blot (WB) was used to detect the protein expression of BCL2 family members in GC cell lines and the manner in which PROTAC‐BCL‐XL kills GC cells. Co‐immunoprecipitation (Co‐IP) was used to investigate the mechanism of A1331852 and ABT‐263 kills GC cell lines. DDPCR, WB, and real‐time PCR (RTPCR) were used to investigate the correlation between DNA, RNA, protein levels, and drug activity. Results The functional assay showed that a subset of GC cell lines relies on BCL‐XL for survival. In gastric cancer cell lines, BCL‐XL inhibitors A1155463 and A1331852 are more sensitive than the pan BCL2 family inhibitor ABT‐263, indicating that ABT‐263 is not an optimal inhibitor of BCL‐XL. VHL‐based PROTAC‐BCL‐XL DT2216 appears to be active in GC cells. DT2216 induces apoptosis of gastric cancer cells in a time‐ and dose‐dependent manner through the proteasome pathway. Statistical analysis showed that the BCL‐XL protein level predicts the response of GC cells to BCL‐XL targeting therapy and BCL2L1 gene CNVs do not reliably predict BCL‐XL expression. Conclusion We identified BCL‐XL as a promising therapeutic target in a subset of GC cases with high levels of BCL‐XL protein expression. Functionally, we demonstrated that both selective BCL‐XL inhibitors and VHL‐based PROTAC BCL‐XL can potently kill GC cells that are reliant on BCL‐XL for survival. However, we found that BCL2L1 copy number variations (CNVs) cannot reliably predict BCL‐XL expression, but the BCL‐XL protein level serves as a useful biomarker for predicting the sensitivity of GC cells to BCL‐XL‐targeting compounds. Taken together, our study pinpointed BCL‐XL as potential druggable target for specific subsets of GC.

Abstract Background Busulfan (BU) is an alkylating agent used as a conditioning agent prior to hematopoietic stem cell (HSC) transplantation as it is known to be cytotoxic to host hematopoietic stem and progenitor cells. The susceptibility of HSCs to BU injury plays an important role in the myeloablative efficacy of BU. Different susceptibilities were demonstrated in genetically diverse (GD) mice in our preliminary research. Methods Three strains of GD mice with different susceptibilities to BU‐induced HSC injury were used for screening biological markers of HSC injury susceptibility in urine. The urine proteins were analyzed using liquid chromatography coupled with tandem mass spectrometry to screen for differentially expressed proteins. Screening for possible biomarkers based on differences in protein expression abundance was validated using enzyme‐linked immunoassay (ELISA). Results Functional analysis showed that the differential proteins were all involved in a series of biological pathways related to cellular senescence, apoptosis, and angiogenesis; whereas the differential proteins of the high‐susceptible strain were enriched for the regulation of bone marrow microenvironment pathways, those of low‐susceptible strain were enriched for the proapoptotic effect of GTPase pathways. Based on protein abundance differences, several urinary proteins that may be indicative of susceptibility were screened, and ELISA validation results showed that angiotensin‐converting enzyme may be a potential biomarker predicting HSC susceptibility for BU conditioning. Conclusions This study indicates that urinary protein levels can reflect differences in susceptibility to BU‐induced HSC injury. Using GD mice to construct genetic difference models will provide preclinical data for screening BU‐related biological markers.

In this paper, a subset-optimized eight-dimensional trellis-coded quadrature amplitude modulation (SO-8DTCM-16QAM) format for higher-order constellations in high-speed optical communications is proposed. This scheme increases the number of subsets of base 2D constellation divisions. On this basis, it is further optimized by using 2D subsets for Cartesian product combinations to obtain 4D subsets and eliminate the combinations with small Euclidean distances. Finally, the 4D subsets are utilized to construct interrelated 8D subsets for trellis coding modulation and signal transmission. The proposed scheme can effectively reduce the decoding complexity and outperforms the conventional scheme at a high signal-to-noise ratio (SNR). Simulation verification of the proposed scheme is carried out, and the results show that the SO-8DTCM-16QAM achieves signal-to-noise ratio (SNR) gains of 1.60 dB, 1.56 dB, 1.51 dB, and 1.33 dB, respectively, compared with the conventional 8D-16QAM signals when BTB and 5/20/30 km optical signal transmission are performed. The SO-8DTCM-16QAM also achieves an SNR gain of 1.86 dB, 1.75 dB, and 1.22 dB at a net transmission rate of 14/21/28 GBaud. In addition, the SO-8DTCM-16/32/64QAM achieves an SNR gain of 1.27 dB, 0.80 dB, and 1.24 dB, respectively, when compared with the unoptimized 8DTCM-16/32/64QAM. Meanwhile, the proposed eight-subset SO-8DTCM-QAM scheme reduces the complexity of the decoding computation in the subset selection part and the constellation point selection part by 93.75% and 50%, respectively, compared with the unoptimized eight-subset and four-subset 8DTCM-QAM schemes. It can be seen that the proposed scheme simultaneously optimizes the transmission performance and complexity of high-speed optical communication systems and has practical application value.

ABSTRACT Central nervous system infections (CNSIs) are common complications after neurosurgery with a poor prognosis. The traditional microbiological culture methodology has a low detection rate and time consuming. Metagenomic next-generation sequencing (mNGS) has demonstrated the advantages of being faster, more accurate, and more comprehensive in clinical microbiology. Previous studies had suggested that mNGS had a high sensitivity in the diagnosis of CNSIs. Whether the application of mNGS has health economic value in clinical applications remains to be studied. We designed a prospective, single-center, superiority randomized controlled trial to compare the cost-effectiveness of mNGS with traditional methods for diagnosing CNSIs using a decision tree model. A total of 204 patients will be enrolled and randomly assigned to either the mNGS group or the traditional method group. The two groups of patients entered different decision points according to different clinical manifestations and examination results. They will be then given treatment decisions by a panel of specialists at the corresponding decision point. The primary outcome is the incremental cost-effectiveness ratio, which is the increased cost for every 1% increase in recovery rate. The secondary outcomes are a comparison of time cost, detection cost, and costs associated with antibiotics treatment between the two groups.IMPORTANCEDiagnosing and treating postoperative central nervous system infections (PCNSIs) remains challenging due to the low detection rate and time-consuming nature of traditional methods for identifying microorganisms in cerebrospinal fluid. Metagenomic next-generation sequencing (mNGS) technology provides a rapid and comprehensive understanding of microbial composition in PCNSIs by swiftly sequencing and analyzing the microbial genome. The current study aimed to assess the economic impact of using mNGS versus traditional bacterial culture-directed PCNSIs diagnosis and therapy in post-neurosurgical patients from Beijing Tiantan Hospital. mNGS is a relatively expensive test item, and whether it has the corresponding health-economic significance in the clinical application of diagnosing intracranial infection has not been studied clearly. Therefore, the investigators hope to explore the clinical application value of mNGS detection in PCNSIs after neurosurgery.

BackgroundFollicular lymphoma (FL), a common indolent B-cell lymphoma, has the potential to transform into an aggressive lymphoma, such as diffuse large B-cell lymphoma (DLBCL). The outcome of patients with transformed follicular lymphoma (tFL) is poor, especially in patients with transformed lymphoma after chemotherapy and patients with progression within 24 months (POD24). Chimeric antigen receptor (CAR) T-cell therapy combined with autologous stem cell transplantation (ASCT) has promising antitumor efficacy.Case presentationHere, we described a 39-year-old male patient who was initially diagnosed with FL that transformed into DLBCL with POD24, CD20 negativity, TP53 mutation, and a bulky mass after 3 lines of therapy, all of which were adverse prognostic factors. We applied a combination approach: CD19 CAR T-cell infusion following ASCT. Ibrutinib was administered continuously to enhance efficacy, DHAP was administered as a salvage chemotherapy, and ICE was administered as a bridging regimen. The patient underwent BEAM conditioning on days -7~ -1, a total of 3.8 × 106/kg CD34+ stem cells were infused on days 01~02, and a total of 108 CAR T cells (relmacabtagene autoleucel, relma-cel, JWCAR029) were infused on day 03. The patient experienced grade 2 cytokine release syndrome (CRS), manifesting as fever and hypotension according to institutional standards. There was no immune effector cell-associated neurotoxicity syndrome (ICANS) after CAR T-cell infusion. Finally, the patient achieved CMR at +1 month, which has been maintained without any other adverse effects.ConclusionThis case highlights the amazing efficacy of CD19 CAR T-cell therapy following ASCT for R/R tFL, thus providing new insight on therapeutic strategies for the future.

Background A recent Mendelian randomization (MR) did not support an effect of the lead interleukin-6 receptor (IL-6 R) variant on risk of pulmonary arterial hypertension (PAH). Thus, we used two sets of genetic instrumental variants (IVs) and publicly available PAH genome-wide association studies (GWAS) to reassess the genetic causal link between IL-6 signaling and PAH. Methods Six independent IL-6 signaling and 34 independent soluble IL-6 receptor (sIL-6 R) genetic IVs from recent MR reports and PAH GWAS including 162,962 European individuals were used to perform this two-sample MR study. Results We found that as IL-6 signaling genetically increased, the risk of PAH reduced using IVW (odds ratio [OR] = 0.023, 95% confidence interval [CI]: 0.0013–0.393; p = .0093) and weighted median (OR = 0.033, 95% CI: 0.0024–0.467; p = .0116). Otherwise, as sIL-6 R genetically increased, the risk of PAH increased using IVW (OR = 1.34, 95% CI: 1.16–1.56; p = .0001), weighted median (OR = 1.36, 95% CI: 1.10–1.68; p = .005), MR-Egger (OR = 1.43, 95% CI: 1.05–1.94; p = .03), and weighted mode (OR = 1.35, 95% CI for OR: 1.12–1.63; p = .0035). Conclusion Our analysis suggested the causal link between genetically increased sIL-6 R and increased risk of PAH and between genetically increased IL-6 signaling and reduced risk of PAH. Thus, higher sIL-6 R levels may be a risk factor for patients with PAH, whereas higher IL-6 signaling may be a protective factor for patients with PAH.

ABSTRACTIn this study, we present a case of acute myeloid leukemia characterized by the t(11;12)(p15;q13) translocation, exhibiting clinical, immunophenotypical, and morphological features consistent with acute promyelocytic leukemia (APL). The RNA sequencing analysis of the patient's bone marrow samples revealed the presence of the NUP98-retinoic acid receptor gamma (RARG) (NUP98::RARG) gene resulting from the translocation. Furthermore, the presence of a mutation in the ARID1B gene in the patient under study indicates a potential association with resistance to all-trans retinoic acid (ATRA).

ABSTRACT Salmonella are intracellular bacterial pathogens for which, as with many of the other Enterobacteriaceae, antibiotic resistance is becoming an increasing problem. New antibiotics are being sought as recommended by the World Health Organization and other international institutions. These must be able to penetrate macrophages, and infect the major host cells and the Salmonella-containing vacuole. This study reports screening a small library of Food and Drug Administration (FDA)-approved drugs for their antibacterial effect in macrophages infected with a rapid-multiplying mutant of Salmonella Enteritidis. The most effective drug that was least toxic for macrophages was Nifuratel, a nitrofuran antibiotic already in use for parasitic infections. In mice, it provided 60% protection after oral infection with a lethal S. Enteritidis dose with reduced bacterial numbers in the tissues. It was effective against different serovars, including multidrug-resistant strains of Salmonella Typhimurium, and in macrophages from different host species and against Listeria monocytogenes and Shigella flexneri. It reduced IL-10 and STAT3 production in infected macrophages which should increase the inflammatory response against Salmonella. IMPORTANCE Salmonella can keep long-term persistence in host's macrophages to evade cellular immune defense and antibiotic attack and exit in some condition and reinfect to cause salmonellosis again. In addition to multidrug resistance, this infection circle causes Salmonella clearance difficult in the host, and so there is a great need for new antibacterial agents that reduce intramacrophage Salmonella survival to block endogenous Salmonella reinfection.

Cancer: vitamin A derivative prevents salivary gland tumors spreading Treatment of salivary gland tumors with a metabolite of vitamin A could help prevent rare cancer from spreading to the lungs. A team led by Xiao-hong Chen and Lu Kong from Capital Medical University in Beijing, China, performed extensive molecular profiling on primary and metastatic tumor cells taken from two patients with advanced salivary gland cancer. Even though these patients’ cancers did not harbor either of two common mutations that are hallmarks of the disease, both of which drive tumor proliferation and spread, the cells did show signs of altered gene expression and faulty molecular signaling consistent with these same mutational profiles. The abnormal signaling could be overcome by treatment with retinoic acid, a derivative of vitamin A that, when given to mouse models of cancer, reduced the development of lung metastases.

In this letter, we propose a novel and straightforward scheme for Q-band (33–50 GHz) millimeter-wave signal generation enabled by a Mach-Zehnder modulator (MZM)-based joint algorithm, which combines probabilistic shaping (PS) and precoding technology, to enhance the anti-interference ability of the transmission system. Based on the proposed scheme, we experimentally demonstrate the generation and transmission of 1.4-Gbaud 46-GHz PS-16-quadrature-amplitude-modulation (PS-16QAM) vector signals, showcasing improved bit-error-ratio (BER) in both standard single-mode fiber (SSMF) and wireless transmission cases. The proposed scheme exhibits a clear advantage in terms of nonlinear interference suppression and satisfies the hard-decision forward-error-correction (HD-FEC) threshold with a BER of 3.8 × 10−3 in radio-over-fiber (RoF) systems.

Abstract Background Metastasis is the primary cause of cancer-related mortality. Metastasis involves a complex multistep process during which individual tumor cells spread primarily through destruction of the endothelial barrier, entering the circulatory system to colonize distant organs. However, the role of the endothelial barrier as the rate-limiting process in tumor metastasis and how these processes affect the regulation of the host microenvironment at the molecular level are poorly understood. Methods Here, we analyzed differentially expressed genes in breast cancer and lung adenocarcinoma, including metastatic and recurrent specimens, using TCGA dataset. The effects of EMCN on endothelial cells in vitro and in vivo were analyzed by assessing angiogenesis and vascular permeability, respectively. We established a syngeneic mouse model of endothelial cell-specific knockout of EMCN (EMCNecko) to study the role of EMCN in tumor growth and metastasis. Transcriptome sequencing, Western blotting, qPCR and immunofluorescence confirmed important factors in the premetastatic niche. A mouse model of allograft tumor resection with lung metastasis was established to confirm the therapeutic effect of a notch inhibitor combined with an anti-TGF-β antibody. Results We found a strong correlation of EMCN deficiency with tumor recurrence and metastasis. Comparative experiments in WT and EMCNecko mice revealed that endothelial EMCN deficiency did not affect primary tumor growth significantly but strongly promoted spontaneous metastasis. EMCN deficiency was associated with gene profiles that regulate cell junctions in vitro and enhance vascular permeability in vivo. Mechanistically, EMCN deficiency mainly affected the host microenvironment and led to the formation of a lung premetastatic niche by recruiting Ly6G+ neutrophils and upregulating MMP9, S100A8/A9 and TGF-β expression. Anti-TGF-β antibody effectively eliminated TGF-β-induced neutrophil polarization, thereby reducing lung metastasis. Notably, the combination of a Notch inhibitor and an anti-TGF-β antibody effectively inhibited tumor growth and lung metastasis and prolonged the survival time of mice. Conclusions We present a new translational strategy of EMCN as a new key player in tumor lung metastasis by affecting the host microenvironment. These findings could provide a sound theoretical basis for clinical treatment.

Abstract Background Bedside assessment of low levels of inspiratory effort, which are probably insufficient to prevent muscle atrophy, is challenging. The flow index, which is derived from the analysis of the inspiratory portion of the flow–time waveform, has been recently introduced as a non-invasive parameter to evaluate the inspiratory effort. The primary objective of the present study was to provide an external validation of the flow index to detect low inspiratory effort. Methods Datasets containing flow, airway pressure, and esophageal pressure (Pes)–time waveforms were obtained from a previously published study in 100 acute brain-injured patients undergoing pressure support ventilation. Waveforms data were analyzed offline. A low inspiratory effort was defined by one of the following criteria, work of breathing (WOB) less than 0.3 J/L, Pes–time product (PTPes) per minute less than 50 cmH2O•s/min, or inspiratory muscle pressure (Pmus) less than 5 cmH2O, adding “or occurrence of ineffective effort more than 10%” for all criteria. The flow index was calculated according to previously reported method. The association of flow index with Pes-derived parameters of effort was investigated. The diagnostic accuracy of the flow index to detect low effort was analyzed. Results Moderate correlations were found between flow index and WOB, Pmus, and PTPes per breath and per minute (Pearson’s correlation coefficients ranged from 0.546 to 0.634, P

A 1-Pbps orbital-angular-momentum fibre-optic transmission system that combines space-division multiplexing and wavelength-division multiplexing in a 34 km 7-core ring-core fibre is demonstrated utilizing low-complexity 4 × 4 MIMO equalization.

Abstract Salivary adenoid cystic carcinoma (SACC) with a unique MYB‐NFIB fusion has been considered an “immune‐cold” tumor, but the mechanisms behind this remain unclear. In this study, we analyzed the immune status of 29 SACC patients and found that most lung metastases exhibited an immunoinflammatory state, in contrast to the primary SACC tissues. Single‐cell sequencing data showed that anergic T‐cell types were low in primary inflammatory tissues, while inflammatory metastatic lung tissues had elevated levels of anergic CD8+ natural killer T (NKT)‐like cells and low levels of memory T cells. Primary exclusive tissues had high levels of myeloid‐derived suppressor cells (MDSCs) and low levels of activated CD8+ NKT‐like cells. These data support the fact that metastatic SACC cells might induce a stronger immune response in the lung. Additionally, an in vivo experiment showed that a minimally invasive SACC cell line with higher expression of human leukocyte antigens ‐B and ‐C induced NKT cell activation in mice and effectively attenuated the incidence of lung metastases caused by a highly invasive SACC cell line. This suggests that NKT therapy may be active in treating SACC lung metastasis. Conclusively, this study sheds light on the immune microenvironment of SACC and highlights the potential of NKT‐based therapy.

In this paper, the preparation process condition of chondroitin sulfate chelated zinc was optimized by orthogonal test. Chondroitin sulfate and zinc sulfate were selected as the raw materials, chelating rate of zinc as evaluation index, the effects of pH, reaction time, mass ratio of chondroitin sulfate to zinc sulfate heptahydrate, and reaction temperature on chelating rate of zinc were investigated by single factor test and orthogonal test. The structural characterization of chondroitin sulfate chelated zinc was analyzed by UV spectroscopy, fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric and X-ray diffraction analysis. The bioavailability of zinc irons in chondroitin sulfate chelated zinc was determined by in vitro simulated gastrointestinal digestion and absorption. The results showed that optimal preparation conditions of chondroitin sulfate chelated zinc were as follows: pH4, reaction time was 1 h, mass ratio was 1:1, and reaction temperature was 30 ℃. Under these conditions, chelating rate of zinc was (80.6%±1.31%). UV spectrum combined with Fourier infrared spectrum analysis showed that chondroitin sulfate chelated zinc was formed by zinc ions combine with hydroxyl, carboxyl, sulfonic groups in chondroitin sulfate. Scanning electron microscopy and X-ray diffraction analysis showed that the micromorphology of chondroitin sulfate chelated zinc was microparticles with crystal structure. Thermogravimetric analysis proved that thermal stability of chondroitin sulfate chelated zinc was better than that of chondroitin sulfate. In vitro simulated gastrointestinal digestion and absorption analysis showed that the bioavailability of chondroitin sulfate chelated zinc was better than that of inorganic zinc salt. The research results would provide theoretical basis and technical support for the development of new zinc supplements.

Most optomechanical sensors rely on the back-action effect between the optical field and a single nanofiber. Here, the collective dynamics of two nanofibers in a hollow-core fiber are explored theoretically, revealing enhanced optical coupling.

Abstract Background Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a nucleic acid‐binding protein. Reportedly, hnRNPK is overexpressed in many human tumors, and such overexpression is associated with poor prognosis, implicating the role of hnRNPK as an oncogene during tumorigenesis. In this study, hnRNPK expression in lung cancer tissues was investigated. Methods Briefly, hnRNPK was knocked down in lung cancer cell lines, and effects of knockdown on the cell proliferation, migration, and cell cycle were assessed using a cell counting kit‐8 (CCK‐8) assay, colony formation assay, transwell assay and flow cytometry. The effects of hnRNPK knockdown on the p53‐dependent signaling pathway were examined using western blotting. Finally, the effect of hnRNPK knockdown on tumor growth was verified in vivo using a lung cancer xenograft mouse model. Results hnRNPK knockdown inhibited the cell proliferation, migration and cell cycle. In addition to phenotypic changes, hnRNPK knockdown upregulated expressions of pCHK1, pCHK2, and p53，p21，cyclin D1, thereby mediating the DNA damage response (DDR). The regulatory function of hnRNPK during p53/p21/cyclin D1 signaling in hnRNPK‐knockdown A549 cells was confirmed by suppressed the protein expression of associated signaling pathways, which inhibited DDR. Conclusion hnRNPK plays a crucial role in the progression of lung cancer, ultimately affecting survival rate. Inhibition of progression of lung cancer cells induced by hnRNPK‐knockdown is dependent on activation of p53 by the p53/p21/cyclin D1 pathway.

Materials with tunable thermal properties enable on-demand control of temperature and heat flow. Here, the authors demonstrate how thermal conductivity of an antiferroelectric solid can be bi-directionally switched to 10% lower and 25% higher values without any moving components.

Fan, Hou et al. investigate the role of phosphodiesterase (PDE) 4 and the PDE4-cAMP-PKA pathway on hypertension, reporting that PDE4D is upregulated in hypertension induced by angiotensin II. The authors also show that Pde4d knockout in mouse SMCs attenuates Ang II-induced hypertension and implicate AMPK signalling and MYPT1-MLC phosphorylation in Ang II-induced SMC contraction.

In this paper, we experimentally demonstrate a net bit rate of 261.7 Gbit/s in a seven-core transmission system with a Kramers–Kronig (KK) receiver. The 10 GBaud 16-level quadrature amplitude modulation (QAM) signal is transmitted over a 2.5 km seven-core fiber, and the relationship between carrier-to-signal power ratio, signal power, frequency spacing, and optical power is analyzed. Moreover, a multiple-input multiple-output (MIMO) Volterra equalization algorithm with crosstalk-dependent steps is proposed to compensate for inter-core crosstalk and impairments induced by other devices. Compared to the single-input single-output (SISO) Volterra equalizer, the CSPR can be reduced by 1.3 dB, and the received power gain can reach up to 0.7 dB.

Abstract In the face of the emerging variants of SARS-CoV-2, there is an urgent need to develop a vaccine that can induce fast, effective, long-lasting and broad protective immunity against SARS-CoV-2. Here, we developed a trimeric SARS-CoV-2 S protein vaccine candidate adjuvanted by PIKA, which can induce robust cellular and humoral immune responses. The results showed a high level of neutralizing antibodies induced by the vaccine was maintained for at least 400 days. In the study of non-human primates, PIKA adjuvanted S-trimer induced high SARS-CoV-2 neutralization titers and protected from virus replication in the lung following SARS-CoV-2 challenge. In addition, the long-term neutralizing antibody response induced by S-trimer vaccine adjuvanted by PIKA could neutralize multiple SARS-CoV-2 variants and there is no obvious different among the SARS- CoV-2 variants of interest or concern, including B.1.351, B.1.1.7, P.1, B.1.617.1 and B.1.617.2 variants. These data support the utility of S-trimer protein adjuvanted by PIKA as a potential vaccine candidate against SARS-CoV-2 infection.

Abstract Based on first-principles calculation, the adsorption of sulfur-based gas molecules (H2S, SO2, SO3) on various metal-decorated phosphorenes is researched systematically. Eleven metals (Li, Na, K, Rb, Cs, Ca, Sr, Ba, Ni, La, Tl) which can avoid the formation of clusters on the phosphorene are considered. Noticeably, all metal decorations can enhance the adsorption strength of phosphorene to sulfur-based gas molecules except for H2S on Tl-decorated phosphorene. Meanwhile, the adsorption energy (E ads) shows the trend of E ads(H2S)

Abstract Background We report a mononucleosis-like illnesses case due to co-infection with severe fever with thrombocytopenia syndrome virus (SFTSV) and spotted fever group rickettsia (SFGR), which to the best of our knowledge, has never been reported . Case presentation A 64-year-old male with an 11-day history of fever, sore throat, malaise, nausea, and non-pruritic rash was admitted to our emergency department. Prior to admission, he was bitten by ticks. Laboratory tests revealed a white blood cell count of 24,460 cells/μL with 25% atypical lymphocytes and 20% mononucleosis, thrombocytopenia. Test results were positive for SFTSV RNA, SFTSV-specific IgM antibody, and SFGR-specific IgM antibody. He was diagnosed with mononucleosis-like illnesses due to co-infection with SFTSV and SFGR. After administration of doxycycline, he recovered completely. Conclusions The clinical presentation may be atypical in co-infection with SFTSV and SFGR. This finding highlighted the importance of considering SFGR infection, as well as a SFSTV and SFGR co-infection for the differential diagnosis of patients bitten by ticks in SFTSV-endemic areas.

Abstract Background A high incidence of malignant tumors, such as post-transplant lymphoproliferative disorders (PTLD), Kaposi sarcoma, and renal cancer is common in solid organ and bone marrow transplant recipients. However, myeloid sarcoma (MS) after renal transplantation has rarely been reported and the diagnosis is challenging due to its low incidence. Case presentation Here, we report a rare case of a 49-year-old man who developed myeloid sarcoma (MS) in the transplanted kidney two years after renal transplantation. Next-generation sequencing (NGS) showed mutations of KRAS and DNMT3A genes in the MS, and no gene mutations in the bone marrow. He presented a normal karyotype of 46, XY. Following treatment with 6 cycles of systemic chemotherapy, the patient was in satisfactory condition with stable serum creatinine (sCr) levels at the 1-year follow-up. In addition, we performed a detailed review with emphasis on the clinical manifestations, and the diagnostic and therapeutic processes of another 7 patients who developed MS following renal transplantation. Conclusions Our report illustrates the clinical utility of comprehensive genomic profiling in benefiting the diagnosis of MS, the selection of therapeutic strategy and the determination of whether MS is donor-derived.

Abstract Acquired resistance to glucocorticoids (GCs) is an obstacle to the effective treatment of leukemia, but the molecular mechanisms of steroid insensitivity have not been fully elucidated. In this study, we established an acquired GC-resistant leukemia cell model and found a long noncoding RNA, HOTAIRM1, was overexpressed in the resistant cells by transcriptional profiling, and was higher expressed in patients with poor prognosis. The whole-genome-binding sites of HOTAIRM1 were determined by ChIRP-seq (chromatin isolation by RNA purification combined with sequencing) analysis. Further study determined that HOTAIRM1 bound to the transcriptional inhibitory region of ARHGAP18 and repressed the expression of ARHGAP18, which led to the increase of RHOA/ROCK1 signaling pathway and promoted GC resistance through antiapoptosis of leukemia cells. The inhibition of ROCK1 in GC-resistant cells could restore GCs responsiveness. In addition, HOTAIRM1 could also act as a protein sequester to prevent transcription factor AML1(acute myeloid leukemia 1) from binding to the regulatory region of ARHGAP18 by interacting with AML1. At last, we also proved AML1 could directly activate the expression of HOTAIRM1 through binding to the promoter of HOTAIRM1, which enriched the knowledge on the regulation of lncRNAs. This study revealed epigenetic causes of glucocorticoid resistance from the perspective of lncRNA, and laid a foundation for the optimization of glucocorticoid-based leukemia treatment strategy in clinic.

Breast cancer (BC) and thyroid cancer (TC) have the highest rate of incidence, especially in women. Previous studies have revealed that lactate provides energetic and anabolic support to cancer cells, thus serving as an important oncometabolite with both extracellular and intracellular signaling functions. However, the correlation of lactate metabolism scores with thyroid and breast cancer immune characteristics remains to be systematically analyzed. To investigate the role of lactate at the transcriptome level and its correlation with the clinical outcome of BC and TC, transcriptome data of 1,217 patients with breast cancer (BC) and 568 patients with thyroid cancer (TC) were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets with their corresponding clinical and somatic mutation data. The lactate metabolism score was calculated based on a single-sample gene set enrichment analysis (ssGSEA). The results showed that lactate metabolism-related genes and lactate metabolism scores was significantly associated with the survival of patients with BRCA and THCA. Notably, the lactate metabolism scores were strongly correlated with human leukocyte antigen (HLA) expression, tumor-infiltrating lymphocyte (TIL) infiltration, and interferon (IFN) response in BC and TC. Furthermore, the lactate metabolism score was an independent prognostic factor and could serve as a reliable predictor of overall survival, clinical characteristics, and immune cell infiltration, with the potential to be applied in immunotherapy or precise chemotherapy of BC and TC.

Abstract Background Myelodysplastic syndrome (MDS) is a group of disorders involving hemopoietic dysfunction leading to leukemia. Although recently progress has been made in identifying underlying genetic mutations, many questions still remain. Animal models of MDS have been produced by introduction of specific mutations. However, there is no spontaneous mouse model of MDS, and an animal model to simulate natural MDS pathogenesis is urgently needed. Methods In characterizing the genetically diverse mouse strains of the Collaborative Cross (CC) we observed that one, designated JUN, had abnormal hematological traits. This strain was thus further analyzed for phenotypic and pathological identification, comparing the changes in each cell population in peripheral blood and in bone marrow. Results In a specific‐pathogen free environment, mice of the JUN strain are relatively thin, with healthy appearance. However, in a conventional environment, they become lethargic, develop wrinkled yellow hair, have loose and light stools, and are prone to infections. We found that the mice were cytopenic, which was due to abnormal differentiation of multipotent bone marrow progenitor cells. These are common characteristics of MDS. Conclusions A mouse strain, JUN, was found displaying spontaneous myelodysplastic syndrome. This strain has the advantage over existing models in that it develops MDS spontaneously and is more similar to human MDS than genetically modified mouse models. JUN mice will be an important tool for pathogenesis research of MDS and for evaluation of new drugs and treatments.

Abstract Background Circular RNA circRHOBTB3 has been characterized as a tumor suppressor in gastric cancer, while its role in hepatocellular carcinoma (HCC) is unknown. This study was carried out to analyze the role of circRHOBTB3 in HCC. Methods In this study, circRHOBTB3, mature miR-18a, and miR-18a precursor in HCC and paired non-cancer tissues were detected by RT-qPCR. The role of circRHOBTB3 in the production of mature miR-18a was explored by transfecting circRHOBTB3 expression vector into HCC cells, followed by RT-qPCR to determine the expression of mature miR-18a and miR-18a precursor. The role of circRHOBTB3 and miR-18a in HCC cell proliferation was studied using CCK-8 assay. Results CircRHOBTB3 was under-expressed in HCC compared to normal tissues. In HCC cells, circRHOBTB3 overexpression decreased mature miR-18a level but not miR-18a precursor. Cell proliferation analysis showed that circRHOBTB3 overexpression decreased cell proliferation while miR-18a overexpression increased cell proliferation. Moreover, circRHOBTB3 suppressed the role of miR-18a in cell proliferation. Conclusions CircRHOBTB3 is downregulated in HCC and may suppress cell proliferation by reducing miR-18a production.

To meet the demands for miniaturization and multi-functional and high-performance electronics applications, the semiconductor industry has shifted its packaging approach to multi-chip vertical stacking. Among the advanced packaging technologies for high-density interconnects, the most persistent factor affecting their reliability is the electromigration (EM) problem on the micro-bump. The operating temperature and the operating current density are the main factors affecting the EM phenomenon. Therefore, when a micro-bump structure is in the electrothermal environment, the EM failure mechanism of the high-density integrated packaging structure must be studied. To investigate the relationship between loading conditions and EM failure time in micro-bump structures, this study established an equivalent model of the vertical stacking structure of fan-out wafer-level packages. Then, the electrothermal interaction theory was used to carry out numerical simulations in an electrothermal environment. Finally, the MTTF equation was invoked, with Sn63Pb37 as the bump material, and the relationship between the operating environment and EM lifetime was investigated. The results showed that the current aggregation was the location where the bump structure was most susceptible to EM failure. The accelerating effect of the temperature on the EM failure time was more obvious at a current density of 3.5 A/cm2, which was 27.51% shorter than 4.5 A/cm2 at the same temperature difference. When the current density exceeded 4.5 A/cm2, the change in the failure time was not obvious, and the maximum critical value of the micro-bump failure was 4 A/cm2~4.5 A/cm2.

Abstract Myelodysplastic syndrome (MDS) is a malignant tumor of the hematological system characterized by long‐term, progressive refractory hemocytopenia. In addition, the risk of leukemia is high, and once it develops, the course of acute leukemia is short with poor curative effect. Animal models are powerful tools for studying human diseases and are highly effective preclinical platforms. Animal models of MDS can accurately show genetic aberrations and hematopoietic clone phenotypes with similar cellular features (such as impaired differentiation and increased apoptosis), and symptoms can be used to assess existing treatments. Animal models are also helpful for understanding the pathogenesis of MDS and its relationship with acute leukemia, which helps with the identification of candidate genes related to the MDS phenotype. This review summarizes the current status of animal models used to research myelodysplastic syndrome (MDS).

Atherosclerotic disease has become the major cause of death worldwide. Smoking, as a widespread independent risk factor, further strengthens the health burden of atherosclerosis. Irisin is a cytokine that increases after physical activity and shows an atheroprotective effect, while its specific mechanism in the process of atherosclerosis is little known. The reversal effect of irisin on intimal thickening induced by smoking-mediated atherosclerosis was identified in Apoe–/– mice through the integrin αVβ5 receptor. Endothelial cells treated with nicotine and irisin were further subjected to RNA-seq for further illustrating the potential mechanism of irisin in atherosclerosis, as well as the wound healing assays, CCK-8 assays, β-gal staining and cell cycle determination to confirm phenotypic alterations. Endothelial differential expressed gene enrichment showed focal adhesion for migration and proliferation, as well as the P53 signaling pathway for cell senescence and cell cycle control. Irisin exerts antagonistic effects on nicotine-mediated migration and proliferation via the integrin αVβ5/PI3K pathway. In addition, irisin inhibits nicotine-mediated endothelial senescence and cell cycle arrest in G0/G1 phase via P53/P21 pathway. This study further illustrates the molecular mechanism of irisin in atherosclerosis and stresses its potential as an anti-atherosclerotic therapy.

This experiment used a parallel array of hot wire probes to simultaneously measure the temperature and velocity fields in the non-isothermal turbulent boundary layer of a rotating straight channel. The Reynolds numbers are 15,000 and 25,000, respectively. The rotation numbers are 0, 0.07, 0.14, 0.21 and 0.28, respectively. The purpose of this study is to calculate the turbulent Prandtl number in a rotating non-isothermal turbulent boundary layer. Due to the difficulty in measuring local turbulent Prandtl numbers, this study focuses on the average turbulent Prandtl numbers in the logarithmic region instead. Under static conditions, this value is taken as 0.9 normally. This research finds that rotation conditions can affect the turbulent Prandtl number by affecting the properties of velocity and temperature boundary layers. The change range of the turbulent Prandtl number is roughly 0.6–1.1. The influence of the leading side is greater than that of the trailing side, especially at high rotation numbers. This can provide validation and guidance for numerical simulation. Other information within the turbulent boundary layer is also discussed. It is hoped that this study would enhance our understanding of the mechanism of turbulent flow in the turbulent layer at rotating conditions.

Abstract Background Head and neck squamous cancer (HNSC) frequently occurs in the clinic. Revealing the role of the genes that correlate with cancer cell outgrowth will contribute to potential treatment target identification and tumor inhibition. Methods The gene expression profiles and gene ontology of the proton‐sensing G‐protein‐coupled receptor OGR1 were analyzed using the TCGA (The Cancer Genome Atlas) database. The effects of sex, age, race, and degree of malignancy on HNSC were investigated, and the survival times of HNSC patients with high or low/medium expression levels of OGR1 were compared. Methylation of the OGR1 promoter CpG sites was also investigated and OGR1‐related genes were analyzed using gene set enrichment analysis. Results OGR1 is overexpressed in HNSC patients. However, compared with the low/median expression group, the high OGR1 expression group did not have different survival rates. The OGR1 expression level differed across sex, age, race, and degree of malignancy, while the methylation of the OGR1 promoter CpG sites was maintained at a similar level. Gene set enrichment analysis revealed that OGR1 was positively correlated with head and neck cancer, cisplatin resistance, hypoxia, angiogenesis, cell migration, and TGF‐β. Conclusion The expression of OGR1 correlated with HNSC progression and survival and thus can serve as a potential treatment target and prognostic marker.