Structural insights into the transcription activation mechanism of the global regulator GlnR from actinobacteria.

In actinobacteria, an OmpR/PhoB subfamily protein called GlnR acts as an orphan response regulator and globally coordinates the expression of genes responsible for nitrogen, carbon, and phosphate metabolism in actinobacteria. Although many researchers have attempted to elucidate the mechanisms of GlnR-dependent transcription activation, progress is impeded by lacking of an overall structure of GlnR-dependent transcription activation complex (GlnR-TAC). Here, we report a co-crystal structure of the C-terminal DNA-binding domain of GlnR (GlnR_DBD) in complex with its regulatory cis-element DNA and a cryo-EM structure of GlnR-TAC which comprises Mycobacterium tuberculosis RNA polymerase, GlnR, and a promoter containing four well-characterized conserved GlnR binding sites. These structures illustrate how four GlnR protomers coordinate to engage promoter DNA in a head-to-tail manner, with four N-terminal receiver domains of GlnR (GlnR-RECs) bridging GlnR_DBDs and the RNAP core enzyme. Structural analysis also unravels that GlnR-TAC is stabilized by complex protein-protein interactions between GlnR and the conserved ß flap, σAR4, αCTD, and αNTD domains of RNAP, which are further confirmed by our biochemical assays. Taken together, these results reveal a global transcription activation mechanism for the master regulator GlnR and other OmpR/PhoB subfamily proteins and present a unique mode of bacterial transcription regulation.

Structure and function of distal and subdistal appendages of the mother centriole.

Centrosomes are composed of centrioles surrounded by pericentriolar material. The two centrioles in G1 phase are distinguished by the localization of their appendages in the distal and subdistal regions; the centriole possessing both types of appendage is older and referred to as the mother centriole, whereas the other centriole lacking appendages is the daughter centriole. Both distal and subdistal appendages in vertebrate cells consist of multiple proteins assembled in a hierarchical manner. Distal appendages function mainly in the initial process of ciliogenesis, and subdistal appendages are involved in microtubule anchoring, mitotic spindle regulation and maintenance of ciliary signaling. Mutations in genes encoding components of both appendage types are implicated in ciliopathies and developmental defects. In this Review, we discuss recent advances in knowledge regarding the composition and assembly of centriolar appendages, as well as their roles in development and disease.

Achiral Solvent Inversed Helical Pathway and Cosolvent Controlled Excited-State "Majority Rule" in Enantiomeric Dansulfonamide Assemblies.

Achiral solvents are commonly utilized to induce the self-assembly of chiral molecules. This study demonstrates that achiral solvents can trigger helicity inversion in the assemblies of dansyl amphiphiles and control the excited-state "majority rule" in assemblies composed of pure enantiomers, through variation of the cosolvent ratio. Specifically, enantiomers of dansyl amphiphiles self-assemble into helical structures with opposite handedness in methanol (MeOH) and acetonitrile (MeCN), together with inversed circular dichroism and circularly polarized luminescence (CPL) signals. When a mixture of MeOH and MeCN is employed, the achiral cosolvents collectively affect the CPL of the assemblies in a way similar to that of "mixed enantiomers". The dominant cosolvent governs the CPL signal. As the cosolvent composition shifts from pure MeCN to MeOH, the CPL signals undergo a significant inversion and amplification, with two maxima observed at ≈20% MeOH and 20% MeCN. This study deepens the comprehension of how achiral solvents modulate helical nanostructures and their excited-state chiroptical properties.

Optimizing resuscitation of the donation after circulatory death heart by mitochondrial protection in a female porcine model.

BACKGROUND: Due to the shortage of donor organs, an increasing number of transplant organs are harvested after circulatory arrest (donation after circulatory death, DCD). Using a translational porcine DCD model, we developed and evaluated a protocol based on cardioprotection by multi-drug postconditioning to optimize resuscitation of DCD hearts by ex situ heart perfusion (ESHP). METHODS: Hearts of female pigs (45.0±4.5 kg) were procured following a clinically identical DCD protocol, consisting of the termination of ventilator support and confirmation of circulatory arrest, followed by a 15-min standoff period. DCD hearts were randomly allocated to ESHP (38.4°C) in the absence (untreated, N=5) or presence (treated, N=5) of a postconditioning treatment added to the perfusate, consisting of Intralipid (1%), sevoflurane (2% v/v), and remifentanil (3 nM). All hearts were perfused with blood and Krebs-Henseleit solution (1:1) for 60 min in Langendorff mode and for additional 300 min in working mode for a total perfusion time of 6 hrs. Oxidative capacity and detailed left ventricular (LV) mechanical function under increasing workload (left atrial pressure 6-12 mmHg) were assessed hourly. LV tissue was snap-frozen at the end of ESHP and used for molecular analyses. RESULTS: LV inotropy (LVdP/dtmax) did not decline over time in treated DCD hearts and was significantly higher at the end of the protocol as compared with untreated DCD hearts (ΔLVdP/dtmax= 440 mmHg/s, p=0.009). Treated DCD hearts exhibited persistently higher LV stroke work index (LVSWI) during the 6-hr period of ESHP, whereas untreated DCD hearts displayed a significant decline (ΔLVSWI=-3.10 mL*mmHg/g, p(time within untreated group)<0.001). Treated DCD hearts displayed higher metabolic activity as measured by oxygen consumption (ΔO2=3.11 mL O2/min/100g; p=0.004), and released lower amounts of cell-free mitochondrial DNA into the perfusate, a marker of potential graft dysfunction. Treated hearts also used fatty acids from Intralipid as an energy source, while untreated DCD hearts showed glyceroneogenesis with triglyceride accumulation and depletion of tricarboxylic acid cycle intermediates, reduced mitochondrial complex I, II, and III activities with accumulation of mitochondrial NADH, and signs of ultrastructural damage. CONCLUSIONS: A translationally relevant protective ESHP protocol consisting of treatment with Intralipid, sevoflurane, and remifentanil markedly accelerated functional recovery and improved viability of DCD hearts.

Structural basis of transcription activation by Rob, a pleiotropic AraC/XylS family regulator.

Rob, which serves as a paradigm of the large AraC/XylS family transcription activators, regulates diverse subsets of genes involved in multidrug resistance and stress response. However, the underlying mechanism of how it engages bacterial RNA polymerase and promoter DNA to finely respond to environmental stimuli is still elusive. Here, we present two cryo-EM structures of Rob-dependent transcription activation complex (Rob-TAC) comprising of Escherichia coli RNA polymerase (RNAP), Rob-regulated promoter and Rob in alternative conformations. The structures show that a single Rob engages RNAP by interacting with RNAP αCTD and σ70R4, revealing their generally important regulatory roles. Notably, by occluding σ70R4 from binding to -35 element, Rob specifically binds to the conserved Rob binding box through its consensus HTH motifs, and retains DNA bending by aid of the accessory acidic loop. More strikingly, our ligand docking and biochemical analysis demonstrate that the large Rob C-terminal domain (Rob CTD) shares great structural similarity with the global Gyrl-like domains in effector binding and allosteric regulation, and coordinately promotes formation of competent Rob-TAC. Altogether, our structural and biochemical data highlight the detailed molecular mechanism of Rob-dependent transcription activation, and provide favorable evidences for understanding the physiological roles of the other AraC/XylS-family transcription factors.

Structural basis of three different transcription activation strategies adopted by a single regulator SoxS.

Transcription activation is established through extensive protein-protein and protein-DNA interactions that allow an activator to engage and remodel RNA polymerase. SoxS, a global transcription activator, diversely regulates subsets of stress response genes with different promoters, but the detailed SoxS-dependent transcription initiation mechanisms remain obscure. Here, we report cryo-EM structures of three SoxS-dependent transcription activation complexes (SoxS-TACI, SoxS-TACII and SoxS-TACIII) comprising of Escherichia coli RNA polymerase (RNAP), SoxS protein and three representative classes of SoxS-regulated promoters. The structures reveal that SoxS monomer orchestrates transcription initiation through specific interactions with the promoter DNA and different conserved domains of RNAP. In particular, SoxS is positioned in the opposite orientation in SoxS-TACIII to that in SoxS-TACI and SoxS-TACII, unveiling a novel mode of transcription activation. Strikingly, two universally conserved C-terminal domains of alpha subunit (αCTD) of RNAP associate with each other, bridging SoxS and region 4 of σ70. We show that SoxS interacts with RNAP directly and independently from DNA, remodeling the enzyme to activate transcription from cognate SoxS promoters while repressing transcription from UP-element containing promoters. Our data provide a comprehensive summary of SoxS-dependent promoter architectures and offer new insights into the αCTD contribution to transcription control in bacteria.

Air pollution and the risk of incident chronic kidney disease in patients with diabetes: An exposure-response analysis.

Impact of air pollution on incident chronic kidney disease (CKD) in diabetic patients is insufficiently studied. We aimed to examine exposure-response associations of PM2.5, PM10, PM2.5-10, NO2, and NOX with incident CKD in diabetic patients in the UK. We also widened exposure level of PM2.5 and examined PM2.5-CKD association in diabetic patients across the entire range of global concentration. Based on data from UK biobank cohort, we applied Cox proportional hazards models and the shape constrained health impact function to investigate the associations between air pollutants and incident CKD in diabetic patients. Global exposure mortality model was applied to combine the PM2.5-CKD association in diabetic patients in the UK with all other published associations. Multiple air pollutants were positively associated with incident CKD in diabetic patients in the UK, with hazard ratios (HRs) of 1.034 (95 %CI: 1.015-1.053) and 1.021 (95 %CI: 1.007-1.036) for every 1 µg/m3 increase in PM2.5 and PM10 concentration, and 1.113 (95 %CI: 1.053-1.177) and 1.058 (95 %CI: 1.027-1.091) for every 10 µg/m3 increase in NO2 and NOX concentration, respectively. For PM2.5-10, associations with CKD in diabetic patients did not reach the statistical significance. Exposure-response associations with CKD in diabetic patients showed a near-linear trend for PM2.5, PM10, NO2, and NOX in the UK, whereas PM2.5-DKD associations in the globe exhibited a non-linear increasing trend. This study supports that air pollution could significantly increase the risk of CKD onset in diabetic patients.

A Laboratory Experimental Study on Enhancing the Oil Recovery Mechanisms of Polymeric Surfactants.

In order to evaluate the physical and chemical properties of polymer surfactants and analyze their oil displacement mechanisms, three types of poly-surfactant used in the Daqing oil field were chosen to be researched, and the oil displacement effects were studied using poly-surfactants of different viscosity, dehydrating rate, and core permeability. The main purpose is to determine the reasonable range of different characteristic indexes of polymeric surfactant flooding. The oil displacement effect of 15 cores was analyzed, and the effects of viscosity, the dehydrating rate of emulsion, and permeability on EOR (Enhanced Oil Recovery) were analyzed. The oil displacement mechanisms of polymeric surfactants were researched using a photolithographic glass core. This paper explores the mechanism underlying production enhancement as an EOR target, while simultaneously conducting laboratory tests to assess the physical and chemical properties of polymeric surfactants. The poly-surfactant agents exhibit a notable increase in viscosity, with the optimal displacement effect observed at a core effective permeability exceeding 400 mD, resulting in a potential EOR of 15% or higher. Moreover, at a viscosity ranging between 40 and 70 mPa·s, the total EOR can reach 73%, with the peak efficiency occurring at a viscosity of 60 mPa·s. The water loss rate of the emulsion, ranging between 30% and 70%, achieves optimal performance at 50%. The poly-surfactants' higher viscosity extends the oil sweep area, enhancing recovery efficiency, and noticeably reducing residual oil compared to water flooding. During poly-surfactant flooding, a substantial amount of residual oil is extracted and transformed into droplets. The rapid emulsification of the polymeric surfactant solution with crude oil forms a stable emulsion, contributing to its significant oil recovery effect. This research provides valuable technical support for EOR in thin and low-quality reservoirs of onshore multi-layered sandstone reservoirs.

Ambient PM2.5 components and prevalence of chronic kidney disease: a nationwide cross-sectional survey in China.

OBJECTIVES: Chronic kidney disease (CKD) is a global public health concern, and accumulating evidence has indicated that air pollution increases the odds of CKD. However, a limited number of studies have examined the long-term effects of ambient fine particulate matter (PM2.5) components on the risk of CKD among general population; thus, major knowledge gaps remain. METHODS: Using data from a nationwide representative cross-sectional survey in China and a validated PM2.5 composition dataset, we established generalized linear models to quantify the association between five major components of PM2.5 and CKD prevalence. RESULTS: There were significant associations between long-term exposure to three PM2.5 components [including black carbon (BC), sulfate (SO42-), organic matter (OM)] and increased odds of CKD prevalence. Along with an interquartile range (IQR) increment in BC (3.3 µg/m3), SO42- (9.7 µg/m3), and OM (16.2 µg/m3) at a 4-year moving average, the odds ratios (ORs) for CKD prevalence were 1.28 (95% CI 1.07, 1.54), 1.23 (95% CI 1.03, 1.45), and 1.23 (95% CI 1.02, 1.47), respectively. We did not detect any significant association of the other two PM2.5 components [nitrate (NO3-) or ammonium (NH4+)] with CKD prevalence. Stratified analyses revealed no differences (P ≥ 0.05) in the effect estimates of subgroups based on administrative region, sex, age, and other demographic characteristics. For instance, along with an IQR increment in BC at a 4-year moving average, the ORs of CKD prevalence among males and females were 1.30 (95% CI 0.98, 1.73) and 1.29 (95% CI 1.01, 1.65), respectively. The odds of CKD were generally higher with increasing PM2.5 composition concentration. CONCLUSIONS: Our study demonstrated that long-term exposure to specific PM2.5 components including BC, SO42-, and OM increased CKD risk in the general population. This study could provide new insights into source-directed PM2.5 control and CKD prevention.

Structural basis of transcription activation by the global regulator Spx.

Spx is a global transcriptional regulator in Gram-positive bacteria and has been inferred to efficiently activate transcription upon oxidative stress by engaging RNA polymerase (RNAP) and promoter DNA. However, the precise mechanism by which it interacts with RNAP and promoter DNA to initiate transcription remains obscure. Here, we report the cryo-EM structure of an intact Spx-dependent transcription activation complex (Spx-TAC) from Bacillus subtilis at 4.2 Å resolution. The structure traps Spx in an active conformation and defines key interactions accounting for Spx-dependent transcription activation. Strikingly, an oxidized Spx monomer engages RNAP by simultaneously interacting with the C-terminal domain of RNAP alpha subunit (αCTD) and σA. The interface between Spx and αCTD is distinct from those previously reported activators, indicating αCTD as a multiple target for the interaction between RNAP and various transcription activators. Notably, Spx specifically wraps the conserved -44 element of promoter DNA, thereby stabilizing Spx-TAC. Besides, Spx interacts extensively with σA through three different interfaces and promotes Spx-dependent transcription activation. Together, our structural and biochemical results provide a novel mechanistic framework for the regulation of bacterial transcription activation and shed new light on the physiological roles of the global Spx-family transcription factors.

A Rolling Bearing Fault Feature Extraction Algorithm Based on IPOA-VMD and MOMEDA.

Since the rolling bearing fault signal captured by a vibration sensor contains a large amount of background noise, fault features cannot be accurately extracted. To address this problem, a rolling bearing fault feature extraction algorithm based on improved pelican optimization algorithm (IPOA)-variable modal decomposition (VMD) and multipoint optimal minimum entropy deconvolution adjustment (MOMEDA) methods is proposed. Firstly, the pelican optimization algorithm (POA) was improved using a reverse learning strategy for dimensional-by-dimensional lens imaging and circle mapping, and the optimization performance of IPOA was verified. Secondly, the kurtosis-square envelope Gini coefficient criterion was used to select the optimal modal components from the decomposed components of the signal, and MOMEDA was used to process the optimal modal components in order to obtain the optimal deconvolution signal. Finally, the Teager energy operator (TEO) was employed to demodulate and analyze the optimally deconvoluted signal in order to enhance the transient shock component of the original fault signal. The effectiveness of the proposed method was verified using simulated and actual signals. The results showed that the proposed method can accurately extract failure characteristics in the presence of strong background noise interference.

Transcriptome Analysis of Rice Embryo and Endosperm during Seed Germination.

Seed germination is a complex, multistage developmental process that is an important step in plant development. In this study, RNA-Seq was conducted in the embryo and endosperm of unshelled germinating rice seeds. A total of 14,391 differentially expressed genes (DEGs) were identified between the dry seeds and the germinating seeds. Of these DEGs, 7109 were identified in both the embryo and endosperm, 3953 were embryo specific, and 3329 were endosperm specific. The embryo-specific DEGs were enriched in the plant-hormone signal-transduction pathway, while the endosperm-specific DEGs were enriched in phenylalanine, tyrosine, and tryptophan biosynthesis. We categorized these DEGs into early-, intermediate-, and late-stage genes, as well as consistently responsive genes, which can be enriched in various pathways related to seed germination. Transcription-factor (TF) analysis showed that 643 TFs from 48 families were differentially expressed during seed germination. Moreover, 12 unfolded protein response (UPR) pathway genes were induced by seed germination, and the knockout of OsBiP2 resulted in reduced germination rates compared to the wild type. This study enhances our understanding of gene responses in the embryo and endosperm during seed germination and provides insight into the effects of UPR on seed germination in rice.

One-Pot Synthesis of N-Doped NiO for Enhanced Photocatalytic CO2 Reduction with Efficient Charge Transfer.

The green and clean sunlight-driven catalytic conversion of CO2 into high-value-added chemicals can simultaneously solve the greenhouse effect and energy problems. The controllable preparation of semiconductor catalyst materials and the study of refined structures are of great significance for the in-depth understanding of solar-energy-conversion technology. In this study, we prepared nitrogen-doped NiO semiconductors using a one-pot molten-salt method. The research shows that the molten-salt system made NiO change from p-type to n-type. In addition, nitrogen doping enhanced the adsorption of CO2 on NiO and increased the separation of photogenerated carriers on the NiO. It synergistically optimized the CO2-reduction system and achieved highly active and selective CO2 photoreduction. The CO yield on the optimal nitrogen-doped photocatalyst was 235 µmol·g-1·h-1 (selectivity 98%), which was 16.8 times that of the p-type NiO and 2.4 times that of the n-type NiO. This can be attributed to the fact that the nitrogen doping enhanced the oxygen vacancies of the NiOs and their ability to adsorb and activate CO2 molecules. Photoelectrochemical characterization also confirmed that the nitrogen-doped NiO had excellent electron -transfer and separation properties. This study provides a reference for improving NiO-based semiconductors for photocatalytic CO2 reduction.

Structural basis for transcription inhibition by E. coli SspA.

Stringent starvation protein A (SspA) is an RNA polymerase (RNAP)-associated protein involved in nucleotide metabolism, acid tolerance and virulence of bacteria. Despite extensive biochemical and genetic analyses, the precise regulatory role of SspA in transcription is still unknown, in part, because of a lack of structural information for bacterial RNAP in complex with SspA. Here, we report a 3.68 Å cryo-EM structure of an Escherichia coli RNAP-promoter open complex (RPo) with SspA. Unexpectedly, the structure reveals that SspA binds to the E. coli σ70-RNAP holoenzyme as a homodimer, interacting with σ70 region 4 and the zinc binding domain of EcoRNAP ß' subunit simultaneously. Results from fluorescent polarization assays indicate the specific interactions between SspA and σ70 region 4 confer its σ selectivity, thereby avoiding its interactions with σs or other alternative σ factors. In addition, results from in vitro transcription assays verify that SspA inhibits transcription probably through suppressing promoter escape. Together, the results here provide a foundation for understanding the unique physiological function of SspA in transcription regulation in bacteria.

Cost-effectiveness of medical migration for chronic kidney disease: a national cross-sectional study in China.

BACKGROUND: The phenomenon of medical migration is common in China. Due to the limited capacity and substantial geographical variation in medical practice, patients with chronic kidney disease (CKD) travel more frequently to seek medical care. We aimed to assess the cost-effectiveness of medical migration for CKD patients in China and provide real-world evidence for the allocation of CKD resources. METHODS: Records of patients with CKD between January 2014 and December 2018 were extracted from a large national database. A patient is defined as a medical migrant if she travelled across the provincial border to a non-residential province to be admitted for inpatient care. The propensity score matching method is used to estimate the effect of medical migration on medical expenditure, length of hospital stay, and in-hospital mortality. The cost-effectiveness is evaluated by comparing the estimated cost per life saved with contemporaneous estimates of the value of a statistical life. RESULTS: Among 4,392,650 hospitalizations with CKD, medical migrants accounted for 4.9% in 2018. Migrant patients were estimated to incur a 26.35% increase in total medical expenditure, experience a 0.24-percentage-points reduction in in-hospital mortality rates, and a 0.49-days reduction in length of hospital stay compared to non-migrant patients. Overall, medical migration among CKD patients incurred an average of 1 million yuan per life saved, which accounted for 20-40% of contemporaneous estimates of the value of a statistical life. Compared with migrant patients with self-payment and commercial insurance, migrant patients with public health insurance (urban basic medical insurance and new rural co-operative medical care) incurred lower cost per life saved. Cost per life saved for CKD patients was similar between female and male, lower among older population, and varied substantially across regions. CONCLUSIONS: The medical care seeking behaviors of CKD patients was prominent and medical resources of kidney care were unevenly allocated across regions. Medical migration led to a reduction in mortality, but was associated with higher medical expenditure. It is imperative to reduce the regional disparity of medical resources and improve the clinical capacity. Our study shows that it is imperative to prioritize resource allocation toward improving kidney health and regional health care planning.

Effects of ambient temperature on hospital admissions for obstructive nephropathy in Wuhan, China: A time-series analysis.

Under the background of global warming, it has been confirmed that heat exposure has a huge impact on human health. The current study aimed to evaluate the effects of daily mean ambient temperature on hospital admissions for obstructive nephropathy (ON) at the population level. A total of 19,494 hospitalization cases for ON in Wuhan, China from January 1, 2015 to December 31, 2018 were extracted from a nationwide inpatient database in tertiary hospitals according to the International Classification of Diseases (ICD)- 10 codes. Daily ambient meteorological and pollution data during the same period were also collected. A quasi-Poisson Generalized Linear Model (GLM) combined with a distributed lag non-linear model (DLNM) was applied to analyze the lag-exposure-response relationship between daily mean temperature and daily hospital admissions for ON. Results showed that there were significantly positive associations between the daily mean temperature and ON hospital admissions. Relative to the minimum-risk temperature (-3.4 â„ƒ), the risk of hospital admissions for ON at moderate hot temperature (25 â„ƒ, 75th percentile) occurred from lag day 4 and stayed to lag day 12 (cumulative relative risk [RR] was 1.846, 95 % confidence interval [CI]: 1.135-3.005, over lag 0-12 days). Moreover, the risk of extreme hot temperature (32 â„ƒ, 99th percentile) appeared immediately and lasted for 8 days (RR = 2.019, 95 % CI: 1.308-3.118, over lag 0-8 days). Subgroup analyses indicated that the middle-aged and elderly (≥45 years) patients might be more susceptible to the negative effects of high temperature, especially at moderate hot conditions. Our findings suggest that temperature may have a significant impact on the acute progression and onset of ON. Higher temperature is associated with increased risks of hospital admissions for ON, which indicates that early interventions should be taken in geographical settings with relatively high temperatures, particularly for the middle-aged and elderly.

LincRNA-p21 Upregulates Nuclear Orphan Receptor Nr4a2 and Aggravates Myocardial Ischemia/Reperfusion Injury via Targeting MiR-466i-5p.

Myocardial ischemia/reperfusion (I/R) injury can bring about more cardiomyocyte death and aggravate cardiac dysfunction, but its pathogenesis remains unclear. This study aimed to investigate the role of long intergenic noncoding RNA-p21 (LincRNA-p21) in myocardial I/R injury and its underlying mechanism. Mice were subjected to myocardial I/R injury by ligation and release of the left anterior descending artery, and HL-1 cardiomyocytes were treated with hydrogen peroxide. Infarct area, cardiac function, and cardiomyocyte apoptosis were determined. Consequently, LincRNA-p21 was found to significantly be elevated both in the reperfused hearts and H2O2-treated cardiomyocytes. Moreover, genetic inhibition of LincRNA-p21 brought about reduced infarct area and improved cardiac function in mice subjected to myocardial I/R injury. LincRNA-p21 knockdown was also demonstrated to inhibit cardiomyocyte apoptosis both in vivo and in vitro. Notably, LincRNA-p21 silencing increased the expression of microRNA-466i-5p (miR-466i-5p) and suppressed the expression of nuclear receptor subfamily 4 group A member 2 (Nr4a2). Mechanically, LincRNA-p21 downregulated and directly interacted with miR-466i-5p, while application of miR-466i-5p inhibitor promoted cardiomyocyte apoptosis that was improved by LincRNA-p21 inhibition. Furthermore, Nr4a2 upregulation caused by LincRNA-p21 overexpression was partially reversed by miR-466i-5p mimics. Thus, LincRNA-p21 positively regulated the expression of Nr4a2, through sponging miR-466i-5p, promoting cardiomyocyte apoptosis in myocardial I/R injury. The current study revealed a novel LincRNA-p21/miR-466i-5p/Nr4a2 pathway for myocardial I/R injury, indicating that LincRNA-p21 may serve as a potential target for future therapy.

Elsholtzia ciliata (Thunb.) Hyland: A Review of Phytochemistry and Pharmacology.

In this paper, the confusion of the sources of medicinal materials was briefly expounded, and the differences among the varieties were pointed out. At the same time, the chemical components and pharmacological properties of Elsholtzia ciliata (Thunb.) Hyland (E. ciliata) were reviewed. The structures of 352 compounds that have been identified are listed. These mainly include flavonoids, terpenoids, phenylpropanoids, alkaloids, and other chemical components. They have antioxidant, anti-inflammatory, antimicrobial, insecticidal, antiviral, hypolipidemic, hypoglycemic, analgesic, antiarrhythmic, antitumor, antiacetylcholinesterase, and immunoregulator activities. At present, there are many researches using essential oil and alcohol extract, and the researches on antioxidant, anti-inflammatory, anti-microbial, and other pharmacological activities are relatively mature. This paper aims to summarize the existing research, update the research progress regarding the phytochemicals and pharmacology of E. ciliate, and to provide convenience for subsequent research.

The Genus Broussonetia: An Updated Review of Phytochemistry, Pharmacology and Applications.

The Broussonetia genus (Moraceae), recognized for its value in many Chinese traditional herbs, mainly includes Broussonetia papyrifera (L.) L'Hér. ex Vent. (BP), Broussonetia kazinoki Siebold (BK), and Broussonetia luzonica (Blanco) Bureau (BL). Hitherto, researchers have found 338 compounds isolated from BP, BK, and BL, which included flavonoids, polyphenols, phenylpropanoids, alkaloids, terpenoids, steroids, and others. Moreover, its active compounds and extracts have exhibited a variety of pharmacological effects such as antitumor, antioxidant, anti-inflammatory, antidiabetic, anti-obesity, antibacterial, and antiviral properties, and its use against skin wrinkles. In this review, the phytochemistry and pharmacology of Broussonetia are updated systematically, after its applications are first summarized. In addition, this review also discusses the limitations of investigations and the potential direction of Broussonetia. This review can help to further understand the phytochemistry, pharmacology, and other applications of Broussonetia, which paves the way for future research.

A unique binding between SspA and RNAP ß'NTH across low-GC Gram-negative bacteria facilitates SspA-mediated transcription regulation.

Stringent starvation protein A (SspA) involved in nucleotide metabolism, acid tolerance and virulence of bacteria has been demonstrated to function as a transcription factor to regulate σ70-dependent gene transcription through interacting with σ70 region 4 and the zinc binding domain (ZBD) of E. coli RNA polymerase (EcoRNAP) ß' subunit simultaneously. Despite extensive biochemical and structural analyses were reported recently, the interactions of SspA with RNAP are not comprehensively understood. Here, we reprocessed our previous cryo-EM dataset of EcoRNAP-promoter open complex with SspA (SspA-RPo) and obtained a significantly improved density map. Unexpectedly, the new map showed that SspA interacts with both N-terminal helix of ß' subunit (ß'ΝΤΗ) and ω subunit, which contributes to stabilize the SspA-EcoRNAP σ70 holoenzyme complex. Sequence alignments and phylogenetic tree analyses of N-terminal sequences of ß' subunit from different classes of bacteria revealed that ß'ΝΤΗ is highly conserved and exclusively found in low-GC-content Gram-negative bacteria that harbor SspA, implying a co-evolution of ß'ΝΤΗ and SspA. The transcription assays of wild-type SspA and its mutants demonstrated the interaction between SspA and ß'ΝΤΗ facilitates the transcription regulation of SspA. Together, our results provide a more comprehensive insight into the interactions between SspA and RNAP and their roles in bacterial transcription regulation.