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Resistance-Nodulation-Division (RND) efflux pumps are responsible for multidrug resistance in Pseudomonas aeruginosa. In this study, we demonstrate that CpxR, previously identified as a regulator of the cell envelope stress response in Escherichia coli, is directly involved in activation of expression of RND efflux pump MexAB-OprM in P. aeruginosa. A conserved CpxR binding site was identified upstream of the mexA promoter in all genome-sequenced P. aeruginosa strains. CpxR is required to enhance mexAB-oprM expression and drug resistance, in the absence of repressor MexR, in P. aeruginosa strains PA14. As defective mexR is a genetic trait associated with the clinical emergence of nalB-type multidrug resistance in P. aeruginosa during antibiotic treatment, we investigated the involvement of CpxR in regulating multidrug resistance among resistant isolates generated in the laboratory via antibiotic treatment and collected in clinical settings. CpxR is required to activate expression of mexAB-oprM and enhances drug resistance, in the absence or presence of MexR, in ofloxacin-cefsulodin-resistant isolates generated in the laboratory. Furthermore, CpxR was also important in the mexR-defective clinical isolates. The newly identified regulatory linkage between CpxR and the MexAB-OprM efflux pump highlights the presence of a complex regulatory network modulating multidrug resistance in P. aeruginosa.

In the past decade, many long noncoding RNAs (lncRNAs) have been identified and their in vitro functions defined, although in some cases their functions in vivo remain less clear. Moreover, unlike nuclear lncRNAs, the roles of cytoplasmic lncRNAs are less defined. Here, using a gene trapping approach in mouse embryonic stem cells, we identify Caren (short for cardiomyocyte-enriched noncoding transcript), a cytoplasmic lncRNA abundantly expressed in cardiomyocytes. Caren maintains cardiac function under pathological stress by inactivating the ataxia telangiectasia mutated (ATM)-DNA damage response (DDR) pathway and activating mitochondrial bioenergetics. The presence of Caren transcripts does not alter expression of nearby ( cis ) genes but rather decreases translation of an mRNA transcribed from a distant gene encoding histidine triad nucleotide-binding protein 1 (Hint1), which activates the ATM-DDR pathway and reduces mitochondrial respiratory capacity in cardiomyocytes. Therefore, the cytoplasmic lncRNA Caren functions in cardioprotection by regulating translation of a distant gene and maintaining cardiomyocyte homeostasis. Long noncoding RNAs (lncRNAs) have been shown to play a role in cardiac physiology and disease. Here the authors identify the lncRNA Caren as a cytoplasmic RNA that decreases the translation of a distant gene encoding Hint1, thereby maintaining cardiomyocyte function due to inactivation of the DNA damage response and activation of mitochondrial bioenergetics.

Re-engineering of complex biological systems (CBS) is an important goal for applications in synthetic biology. Efforts have beenmade to simplify CBS by refactoring a large number of genes with rearranged polycistrons and synthetic regulatory circuits. Here, a posttranslational protein-splicing strategy derived from RNA viruses was exploited to minimize gene numbers of the classic nitrogenase system, where the expression stoichiometry is particularly important. Operon-based nif genes from Klebsiella oxytoca were regrouped into giant genes either by fusing genes together or by expressing polyproteins that are subsequently cleaved with Tobacco Etch Virus protease. After several rounds of selection based on protein expression levels and tolerance toward a remnant C-terminal ENLYFQ-tail, a system with only five giant genes showed optimal nitrogenase activity and supported diazotrophic growth of Escherichia coli. This study provides an approach for efficient translation from an operon-based system into a polyprotein-based assembly that has the potential for portable and stoichiometric expression of the complex nitrogenase system in eukaryotic organisms.

The optimization of the operation strategy for building HVAC systems is the key to achieving energy conservation and consumption reduction in air-conditioning systems. This study proposes an online real-time control strategy for the air-conditioning water system based on the model predictive control (MPC) principle, implemented and validated on the integrated energy experimental platform. The experimental system simulates load generation and dissipation processes using a water tank, where hourly varying heating power output emulates the dynamic cooling loads of buildings. By regulating the chilled water system through different algorithms, the temperature tracking control performance and cooling supply regulation accuracy were rigorously validated. The control module was written in the Python 3.8 environment, and Niagara 4 software was used as an intermediate software to achieve data interaction and logical control with the laboratory system. The experimental results show that this algorithm can follow the hourly optimized parameters with a low overshoot in the short-term domain. Meanwhile, it can achieve the optimal control of cooling capacity and energy consumption in the long-term domain. Compared with the PID strategy, the temperature following control accuracy can be improved by 9.64%, and the cooling capacity can be saved by 6.24%. Compared with the day-ahead MPC algorithm, the temperature following control accuracy can be relatively improved by 16.52%, and the cooling capacity can be saved by 1.24%.

Sarcopenia due to loss of skeletal muscle mass and strength leads to physical inactivity and decreased quality of life. The number of individuals with sarcopenia is rapidly increasing as the number of older people increases worldwide, making this condition a medical and social problem. Some patients with sarcopenia exhibit accumulation of peri-muscular adipose tissue (PMAT) as ectopic fat deposition surrounding atrophied muscle. However, an association of PMAT with muscle atrophy has not been demonstrated. Here, we show that PMAT is associated with muscle atrophy in aged mice and that atrophy severity increases in parallel with cumulative doses of PMAT. We observed severe muscle atrophy in two different obese model mice harboring significant PMAT relative to respective control non-obese mice. We also report that denervation-induced muscle atrophy was accelerated in non-obese young mice transplanted around skeletal muscle with obese adipose tissue relative to controls transplanted with non-obese adipose tissue. Notably, transplantation of obese adipose tissue into peri-muscular regions increased nuclear translocation of FoxO transcription factors and upregulated expression FoxO targets associated with proteolysis (Atrogin1 and MuRF1) and cellular senescence (p19 and p21) in muscle. Conversely, in obese mice, PMAT removal attenuated denervation-induced muscle atrophy and suppressed upregulation of genes related to proteolysis and cellular senescence in muscle. We conclude that PMAT accumulation accelerates age- and obesity-induced muscle atrophy by increasing proteolysis and cellular senescence in muscle.

Background The current discussion comprehensively addresses the injury and treatment of discoid lateral meniscus. However, it is important to note that an unfavorable biomechanical environment caused by the discoid lateral meniscus not only leads to self-injury but also has a significant impact on adjacent structures. Therefore, the aim of this study was to investigate the relationship between discoid lateral meniscus and injuries in both the meniscus and cartilage within the total tibiofemoral joint. Methods Patients undergoing knee magnetic resonance imaging examinations at our outpatient clinic were screened, and a total of 278 patients were enrolled in the discoid lateral meniscus group, while 279 patients were enrolled in the non-discoid meniscus group. The type of discoid lateral meniscus was classified according to the Watanabe classification, while meniscal and articular cartilage injuries were classified using the Stoller and Hepple classifications, respectively. The prevalence of discoid lateral meniscus and injuries to the meniscus and articular structures within the tibiofemoral joint in the general population was assessed, along with their relationship. Results The prevalence of discoid lateral meniscus was 8.5%, while the incidence of tibiofemoral joint injury was 10%. Notably, the discoid lateral meniscus group exhibited a significantly higher incidence of tibiofemoral joint injury (P < 0.001). Among these cases, there were 93 patients with type I discoid lateral meniscus and 185 patients with type II discoid lateral meniscus. Specifically, the type I discoid lateral meniscus group showed a significantly higher percentage of lateral meniscus injuries ( P  < 0.005), whereas the type II discoid lateral meniscus group demonstrated a significantly higher percentage of medial tibiofemoral joint injuries ( P  < 0.005). Conclusion The lateral discoid meniscus causes knee joint biomechanical abnormalities, increasing the risk of injury and degeneration in the tibiofemoral joint. Type I lateral discoid meniscus is prone to self-tearing and secondary ipsilateral articular cartilage injury. Type II lateral discoid meniscus may remain intact over a wider age range but is associated with a higher risk of injury and degeneration in the medial tibiofemoral joint.

In the present work, an experimental investigation is performed to assess the thermal and electrical performance of a photovoltaic solar panel cooling with multi-walled carbon nanotube–water/ethylene glycol (50:50) nano-suspension (MWCNT/WEG50). The prepared nanofluid was stabilized using an ultrasonic homogenizer together with the addition of 0.1vol% of nonylphenol ethoxylates at pH = 8.9. To reduce the heat loss and to improve the heat transfer rate between the coolant and the panel, a cooling jacket was designed and attached to the solar panel. It was also filled with multi-walled carbon nanotube–paraffin phase change material (PCM) and the cooling pipes were passed through the PCM. The MWCNT/WEG50 nanofluid was introduced into the pipes, while the nano-PCM was in the cooling jacket. The electrical and thermal power of the system and equivalent electrical–thermal power of the system was assessed at various local times and at different mass fractions of MWCNTs. Results showed that with an increase in the mass concentration of the coolant, the electricity and power production were promoted, while with an increase in the mass concentration of the nanofluid, the pumping power was augmented resulting in the decrease in the thermal–electrical equivalent power. It was identified that a MWCNT/WEG50 nano-suspension at 0.2wt% can represent the highest thermal and electrical performance of 292.1 W/m2. It was also identified that at 0.2wt%, ~45% of the electricity and 44% of the thermal power can be produced with a photovoltaic (PV) panel between 1:30 pm to 3:30 pm.

This study aimed to explore the relationship between female age and pregnancy outcomes in patients undergoing their first elective single embryo transfer (eSET) of in vitro fertilization (IVF) cycles. The retrospective cohort study encompassed 7089 IVF/intracytoplasmic sperm injection (ICSI) patients of the Reproductive Medicine Center, Henan Provincial Peoples’ Hospital of China, from September 1, 2016, to May 31, 2022. Patients all received the first eSET in their IVF/ICSI cycles. A generalized additive model (GAM) was employed to examine the the dose–response correlation between age and pregnancy outcomes, namely the clinical pregnancy rate (CPR) and ongoing pregnancy rate (OPR). Logistic regression model was employed to ascertain the correlation between the CPR/OPR and age. The study cohort has an average age of 30.74; 3843 patients got clinical pregnancy rate of 61.40% and ongoing pregnancy rate of 54.21%. The multiple pregnancy rate of is 1.24%. For patients aged 34 and above, the CPR decreased by 10% for every 1-year increase in age (adjusted OR 0.90, 95% CI 0.84–0.96, p < 0.0001). Similarly, the OPR decreased by 16% for every 1-year increase in age (adjusted OR 0.84, 95% CI 0.81–0.88, p < 0.0001). Patients aged 35–37 years had an acceptable OPR of 52.4% after eSET, with a low multiple pregnancy rate (1.1%). Pregnancy outcomes were significantly better in blastocyst cycles compared to cleavage embryo cycles, and this trend was more pronounced in older patients. There was a non-linear relationship between female age and pregnancy outcomes in patients undergoing their first eSET cycles. The clinical pregnancy rate and ongoing pregnancy rate decreased significantly with age, especially in women older than 34 years. For patients under 37 years old, single embryo transfer should be prioritized. For patients over 38 years old with available blastocysts, eSET is also recommended.

Both pulmonary arterial hypertension (PAH) and chronic obstructive pulmonary disease (COPD) are risk factors for coronavirus disease 2019 (COVID-19). Patients with lung injury and altered pulmonary vascular anatomy or function are more susceptible to infections. The purpose of the study is to ascertain whether individuals with COPD or PAH are affected synergistically by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data sources for the construction of a protein-protein interaction (PPI) network and the identification of differentially expressed genes (DEGs) included three RNA-seq datasets from the GEO database (GSE147507, GSE106986, and GSE15197). Then, relationships between miRNAs, common DEGs, and transcription factor (TF) genes were discovered. Functional analysis using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and other databases, as well as the forecasting of antiviral medications for COPD and PAH patients infected with SARS-CoV-2, were also performed. Eleven common DEGs were found in the three datasets, and their biological functions were primarily enriched in the control of protein modification processes, particularly phosphorylation. Growth factor receptor binding reflects molecular function. KEGG analysis indicated that co-DEGs mainly activate Ras, and PI3K-Akt signaling pathways and act on focal adhesions. NFKB1 interacted with HSA-miR-942 in the TF-miRNA-DEGs synergistic regulatory network. Acetaminophen is considered an effective drug candidate. There are some connections between COPD and PAH and the development of COVID-19. This research could aid in developing COVID-19 vaccines and medication candidates that would work well as COVID-19 therapies.

In the present study, we report the results of the experiments conducted on the convective heat transfer of graphene nano-platelets dispersed in water-ethylene glycol. The graphene nano-suspension was employed as a coolant inside a micro-channel and heat-transfer coefficient (HTC) and pressure drop (PD) values of the system were reported at different operating conditions. The results demonstrated that the use of graphene nano-platelets can potentially augment the thermal conductivity of the working fluid by 32.1% (at wt. % = 0.3 at 60 °C). Likewise, GNP nano-suspension promoted the Brownian motion and thermophoresis effect, such that for the tests conducted within the mass fractions of 0.1%–0.3%, the HTC of the system was improved. However, a trade-off was identified between the PD value and the HTC. By assessing the thermal performance evaluation criteria (TPEC) of the system, it was identified that the thermal performance of the system increased by 21% despite a 12.1% augmentation in the PD value. Furthermore, with an increment in the fluid flow and heat-flux applied to the micro-channel, the HTC was augmented, showing the potential of the nano-suspension to be utilized in high heat-flux thermal applications.