Importance and vulnerability of the world's water towers.

Mountains are the water towers of the world, supplying a substantial part of both natural and anthropogenic water demands1,2. They are highly sensitive and prone to climate change3,4, yet their importance and vulnerability have not been quantified at the global scale. Here we present a global water tower index (WTI), which ranks all water towers in terms of their water-supplying role and the downstream dependence of ecosystems and society. For each water tower, we assess its vulnerability related to water stress, governance, hydropolitical tension and future climatic and socio-economic changes. We conclude that the most important (highest WTI) water towers are also among the most vulnerable, and that climatic and socio-economic changes will affect them profoundly. This could negatively impact 1.9 billion people living in (0.3 billion) or directly downstream of (1.6 billion) mountainous areas. Immediate action is required to safeguard the future of the world's most important and vulnerable water towers.

Kidney Angiotensin in Cardiovascular Disease: Formation and Drug Targeting.

The concept of local formation of angiotensin II in the kidney has changed over the last 10-15 years. Local synthesis of angiotensinogen in the proximal tubule has been proposed, combined with prorenin synthesis in the collecting duct. Binding of prorenin via the so-called (pro)renin receptor has been introduced, as well as megalin-mediated uptake of filtered plasma-derived renin-angiotensin system (RAS) components. Moreover, angiotensin metabolites other than angiotensin II [notably angiotensin-(1-7)] exist, and angiotensins exert their effects via three different receptors, of which angiotensin II type 2 and Mas receptors are considered renoprotective, possibly in a sex-specific manner, whereas angiotensin II type 1 (AT1) receptors are believed to be deleterious. Additionally, internalized angiotensin II may stimulate intracellular receptors. Angiotensin-converting enzyme 2 (ACE2) not only generates angiotensin-(1-7) but also acts as coronavirus receptor. Multiple, if not all, cardiovascular diseases involve the kidney RAS, with renal AT1 receptors often being claimed to exert a crucial role. Urinary RAS component levels, depending on filtration, reabsorption, and local release, are believed to reflect renal RAS activity. Finally, both existing drugs (RAS inhibitors, cyclooxygenase inhibitors) and novel drugs (angiotensin receptor/neprilysin inhibitors, sodium-glucose cotransporter-2 inhibitors, soluble ACE2) affect renal angiotensin formation, thereby displaying cardiovascular efficacy. Particular in the case of the latter three, an important question is to what degree they induce renoprotection (e.g., in a renal RAS-dependent manner). This review provides a unifying view, explaining not only how kidney angiotensin formation occurs and how it is affected by drugs but also why drugs are renoprotective when altering the renal RAS. SIGNIFICANCE STATEMENT: Angiotensin formation in the kidney is widely accepted but little understood, and multiple, often contrasting concepts have been put forward over the last two decades. This paper offers a unifying view, simultaneously explaining how existing and novel drugs exert renoprotection by interfering with kidney angiotensin formation.

A sex- and site-specific relationship between body mass index and osteoarthritis: evidence from observational and genetic analyses.

OBJECTIVE: We primarily aimed to investigate whether there are phenotypic and genetic links underlying body mass index (BMI) and overall osteoarthritis (OA). We then intended to explore whether the relationships differ across sexes and sites. METHOD: We first evaluated the phenotypic association between BMI and overall OA using data from the UK Biobank. We then investigated the genetic relationship leveraging summary statistics of the hitherto largest genome-wide association studies performed for BMI and overall OA. Finally, we repeated all analyses in a sex- (female, male) and site- (knee, hip, spine) specific manner. RESULTS: Observational analysis suggested an increased hazard of diagnosed OA per 5 kg/m2 increment in BMI (hazard ratio = 1.38, 95% confidence interval (CI) = 1.37-1.39). A positive overall genetic correlation was observed for BMI and OA (rg = 0.43, P = 4.72 × 10-133), corroborated by 11 significant local signals. Cross-trait meta-analysis identified 34 pleiotropic loci shared between BMI and OA, of which seven were novel. Transcriptome-wide association study revealed 29 shared gene-tissue pairs, targeting nervous, digestive, and exo/endocrine systems. Mendelian randomization demonstrated a robust BMI-OA causal relationship (odds ratio = 1.47, 95% CI = 1.42-1.52). A similar pattern of effects was observed in sex- and site-specific analyses, with BMI affecting OA comparably in both sexes and most strongly in the knee. CONCLUSION: Our work demonstrates an intrinsic relationship underlying BMI and overall OA, reflected by a pronounced phenotypic association, significant biological pleiotropy, and a putative causal link. Stratified analysis further reveals that the effects are distinct across sites and comparable across sexes.

Amplification of a terahertz wave via stimulated Raman scattering.

Extremely strong terahertz (THz) waves are desperately demanded for investigating nonlinear physics, spectroscopy, and imaging in the THz range. However, traditional crystal-/semiconductor-based THz sources have limitations of reaching extremely high amplitude due to the damage threshold of devices. Here, by introducing Raman amplification to the THz range, we propose a novel, to the best of our knowledge, scheme to amplify THz waves in plasma. A long-pulse CO2 pump laser transfers its energy to a multicycle, 10-THz seed in a two-step plasma. By one-dimensional simulations, a 0.87-GV/m, 1.2-ps-duration THz seed is amplified to 10 GV/m in a 5.7-mm-long plasma with an amplification efficiency approaching 1%. The method provides a new technology to manipulate the intensity of THz waves.

Sensitivity of Mucor piriformis to Natamycin and Efficacy of Natamycin Alone and with Salt and Heat Treatments Against Mucor Rot of Stored Mandarin Fruit.

Mucor rot caused by Mucor piriformis is an emerging postharvest disease of mandarin fruit in California. Natamycin is a newly registered biofungicide for postharvest use on citrus and some other fruits. In the study, baseline sensitivity to natamycin in 50 isolates of M. piriformis was determined in vitro. The mean EC50 (effective concentration to inhibit sporangiospore germination by 50%) and MIC (minimum inhibitory concentration to inhibit mycelial growth by 100%) values were 0.59 µg/ml and less than 1.0 µg/ml, respectively. Natamycin at the label rate of 920 µg/ml alone or in combination with 3% potassium sorbate (PS) or 3% sodium carbonate (SC) applied at 20 or 50°C was evaluated for control of Mucor rot on inoculated 'Tango' mandarin fruit. Natamycin alone reduced Mucor rot incidence on stored mandarin fruit from 100% among nontreated control fruit to approximately 30%, a reduction of more than 70% compared to the nontreated control, while 3% PS and 3% SC had no to little control. When applied at 50°C, natamycin and 3% PS reduced Mucor rot incidence by 65.0 and 31.2%, respectively; while natamycin in combination with 3% PS reduced disease incidence by 92.5% compared to the nontreated control after 2 weeks of storage at 5°C. This combined treatment remained effective even when the application of the treatment was delayed for 6 and 12 h after inoculation. However, the effectiveness of the treatments declined when storage was extended to 3 or 4 weeks. Natamycin can be an effective tool to control Mucor rot on mandarin fruit, and minimizing the period of extended storage could help maintain the control efficacy of natamycin.

Away Rotation Applications in Emergency Medicine: Medical Student Behaviors, Outcomes, and Stressors.

BACKGROUND: Completing an emergency medicine (EM) away rotation is integral to matching successfully into an EM residency program. The demand for EM away rotations (ARs) drives students to submit numerous applications without evidence-based recommendations to guide stakeholders on the approach or number to submit. OBJECTIVES: We conducted a survey study of EM-bound fourth-year medical students to gain insight into their AR application experiences, outcomes, and perceptions. METHODS: We distributed a 40-item questionnaire to EM applicants in Fall 2018 via e-mail through the Clerkship Directors in Emergency Medicine, Council of Residency Directors in EM, and Emergency Medicine Residents' Association listservs. Responses were evaluated using quantitative and qualitative analysis. Primary outcomes were the number of AR applications submitted and AR offers received by students. Secondary outcomes were students' self-assessment of their competitiveness, differences in AR application numbers by degree type, sources of student advising, and student perceptions of the AR application process. RESULTS: There were 253 respondents, consisting of 192 allopathic (MD) and 61 osteopathic (DO) medical students, who met the inclusion criteria, representing about 10% of the applicant pool. On average, students submitted 13.97 applications (95% confidence interval [CI] 11.59-16.35), received 3.25 offers (95% CI 3.01-3.49), and accepted 2.22 offers (95% CI 2.08-2.36). DO candidates submitted twice as many applications as MD candidates while experiencing a similar rate of offers received. Peer influence (n = 154, 61%), peer online advising networks (n = 83, 33%), and self-assessment (n = 114, 45%) were the most often reported causes of increased applications; cost (n = 104, 41%) and geographic limitations (n = 114, 45%) were the most often reported causes of decreased applications. Open-response analysis revealed frustration with lack of standardization (n = 44, 29.5%), insufficient transparency on available positions (n = 37, 24.8%), limited communication (n = 30, 20.1%), and cost (n = 12, 8.1%). CONCLUSIONS: This study showed that, as a whole, students received one away rotation offer for every four to five applications submitted. It clarified factors contributing to increased EM away rotation application submissions and associated stressors inherent in the application experience. Our findings offer insights to inform advising recommendations. They also suggest that stakeholders consider standardizing the process and improve communication over spot availability and application status.

Angiotensin II and AT1a Receptors in the Proximal Tubules of the Kidney: New Roles in Blood Pressure Control and Hypertension.

Contrary to public perception, hypertension remains one of the most important public health problems in the United States, affecting 46% of adults with increased risk for heart attack, stroke, and kidney diseases. The mechanisms underlying poorly controlled hypertension remain incompletely understood. Recent development in the Cre/LoxP approach to study gain or loss of function of a particular gene has significantly helped advance our new insights into the role of proximal tubule angiotensin II (Ang II) and its AT1 (AT1a) receptors in basal blood pressure control and the development of Ang II-induced hypertension. This novel approach has provided us and others with an important tool to generate novel mouse models with proximal tubule-specific loss (deletion) or gain of the function (overexpression). The objective of this invited review article is to review and discuss recent findings using novel genetically modifying proximal tubule-specific mouse models. These new studies have consistently demonstrated that deletion of AT1 (AT1a) receptors or its direct downstream target Na+/H+ exchanger 3 (NHE3) selectively in the proximal tubules of the kidney lowers basal blood pressure, increases the pressure-natriuresis response, and induces natriuretic responses, whereas overexpression of an intracellular Ang II fusion protein or AT1 (AT1a) receptors selectively in the proximal tubules increases proximal tubule Na+ reabsorption, impairs the pressure-natriuresis response, and elevates blood pressure. Furthermore, the development of Ang II-induced hypertension by systemic Ang II infusion or by proximal tubule-specific overexpression of an intracellular Ang II fusion protein was attenuated in mutant mice with proximal tubule-specific deletion of AT1 (AT1a) receptors or NHE3. Thus, these recent studies provide evidence for and new insights into the important roles of intratubular Ang II via AT1 (AT1a) receptors and NHE3 in the proximal tubules in maintaining basal blood pressure homeostasis and the development of Ang II-induced hypertension.

[Effects of plasma lipopolysaccharide changes on platelet release of vascular endothelial growth factor and thromobospondin-1 in patients with cirrhotic portal hypertension after TIPS procedure].

Objective: To investigate the effects of plasma lipopolysaccharide (LPS) concentration changes on platelet release of vascular endothelial growth factor (VEGF) and thrombospondin (TSP)-1 in patients with decompensated cirrhotic portal hypertension after transjugular intrahepatic portosystemic shunt (TIPS) procedure. Methods: 169 cases with cirrhotic portal hypertension were enrolled, of which 81 cases received TIPS treatment. LPS, VEGF, and TSP-1 concentrations with different Child-Pugh class in peripheral blood plasma of patients were measured. After pre-incubation of normal human platelets with different concentrations of LPS and stimulated by collagen in vitro, platelet PAC-1 expression rate, VEGF, and TSP-1 concentrations were detected. PAC-1 expression rate and the concentrations of LPS, VEGF and TSP-1 in peripheral blood plasma of patients before and after TIPS procedure were detected. The relationship between plasma LPS, VEGF and TSP-1 concentrations and Child-Pugh score changes in patients after TIPS procedure was analyzed. Statistical analysis was performed by t-test, one-way ANOVA or Pearson's rho according to different data. Results: Plasma LPS and TSP-1 concentrations were significantly higher in Child-Pugh class C patients than class A and B, but the concentration of plasma VEGF was significantly lower than class A and B (P < 0.01). In vitro experiments showed that concentration of LPS, TSP-1, and platelet PAC-1 expression rate was higher in the supernatant, but the difference in the concentration of VEGF in the supernatant was not statistically significant. Portal vein pressure and platelet activation were significantly decreased (P < 0.01) in patients after TIPS procedure. Portal venous pressure, platelet activation, plasma LPS, and TSP-1 levels were significantly decreased continuously, while VEGF levels were significantly increased continuously after TIPS procedure. Plasma LPS concentration was positively correlated with TSP-1 concentration (r = 0.506, P < 0.001), and negatively correlated with VEGF concentration (r = -0.167, P = 0.010). Child-Pugh score change range was negatively correlated with change range of plasma VEGF concentration (r = -0.297, P = 0.016), and positively correlated with change range of plasma TSP-1 concentration (r = 0.145, P = 0.031) after TIPS. Conclusion: Portal venous pressure gradient, plasma LPS concentration and corresponding platelet activation was decreased in cirrhotic portal hypertension after TIPS procedure, and with TSP-1 reduction and VEGF elevation it is possible to reduce the liver function injury caused by portal venous shunt.

Sex differences in angiotensin II-induced hypertension and kidney injury: role of AT1a receptors in the proximal tubule of the kidney.

In the present study, we tested the hypothesis that there are significant sex differences in angiotensin II (Ang II)-induced hypertension and kidney injury using male and female wildtype (WT) and proximal tubule-specific AT1a receptor knockout mice (PT-Agtr1a-/-). Twelve groups (n=8-12 per group) of adult male and female WT and PT-Agtr1a-/- mice were infused with a pressor dose of Ang II via osmotic minipump for 2 weeks (1.5 mg/kg/day, i.p.) and simultaneously treated with or without losartan (20 mg/kg/day, p.o.) to determine the respective roles of AT1a receptors in the proximal tubules versus systemic tissues. Basal systolic, diastolic, and mean arterial pressure were approximately 13 ± 3 mmHg lower (P<0.01), while basal 24-h urinary Na+, K+, and Cl- excretion were significantly higher in both male and female PT-Agtr1a-/- mice than WT controls (P<0.01) without significant sex differences between different strains. Both male and female WT and PT-Agtr1a-/- mice developed hypertension (P<0.01), and the magnitudes of the pressor responses to Ang II were similar between male and female WT and PT-Agtr1a-/- mice (n.s.). Likewise, Ang II-induced hypertension was significantly attenuated in both male and female PT-Agtr1a-/- mice (P<0.01). Furthermore, losartan attenuated the hypertensive responses to Ang II to similar extents in both male and female WT and PT-Agtr1a-/- mice. Finally, Ang II-induced kidney injury was attenuated in PT-Agtr1a-/- mice (P<0.01). In conclusion, the present study demonstrates that deletion of AT1a receptors in the proximal tubules of the kidney attenuates Ang II-induced hypertension and kidney injury without revealing significant sex differences.

Upregulated E3 ligase tripartite motif-containing protein 21 in psoriatic epidermis ubiquitylates nuclear factor-κB p65 subunit and promotes inflammation in keratinocytes.

BACKGROUND: Tripartite motif-containing protein 21 (Trim21) is an E3 ubiquitin-protein ligase that plays pivotal roles in various diseases. However, its role in mediating keratinocyte inflammation, which is a hallmark of psoriasis, has not been thoroughly elucidated. OBJECTIVES: To clarify whether Trim21 plays a pivotal role in regulating keratinocyte inflammation in psoriasis, while focusing on identifying key Trim21 substrates involved in mediating proinflammatory cytokine and chemokine production. MATERIALS AND METHODS: Cytokine and chemokine secretion was examined by quantitative real-time polymerase chain reaction (qPCR) in Trim21-knockdown human keratinocytes. Downstream pathways and substrates of Trim21 were evaluated using immunoblotting, immunoprecipitation and immunofluorescence. The influence of Trim21 ubiquitination on its substrates was tested by in vitro ubiquitination assay, immunoprecipitation and immunofluorescence. The effectiveness of targeting Trim21 for psoriasis treatment was assessed in vivo with haematoxylin and eosin staining, immunofluorescence and qPCR. RESULTS: Knocking down Trim21 expression alleviated keratinocyte inflammation. Trim21 colocalized with p65/nuclear factor (NF)-κB in the cytosol and physically bound and ubiquitinated p65 via a lysine 63 (K63) linkage. Instead of changing p65 protein stability, Trim21 enhanced the interaction of p65 with IκB kinase, which promoted p65 phosphorylation, nuclear transport and downstream gene activation. Finally, both in vitro and in vivo experiments verified that topical application of Trim21-specific small interfering RNA markedly ameliorated imiquimod-induced psoriasis-like lesions. CONCLUSIONS: Our study confirms that upregulated Trim21 in psoriatic epidermis ubiquitylates p65 and activates the NF-κB pathway, which promotes keratinocyte inflammation. Hence, Trim21 represents a potential target for psoriasis treatment.

Isolation and characterization of endophytic bacteria for controlling root rot disease of Chinese jujube.

AIM: Fusarium oxysporum is the primary pathogen causing root rot disease that severely affects cultivation of jujube fruit in the Xinjiang province of China. The aim of this study was to identify endophytic bacteria in healthy jujube organs that could effectively suppress F. oxysporum growth. METHODS AND RESULTS: Different plant organs (leaves, twigs and roots) were collected from healthy Chinese jujube cultivated in southern Xinjiang province of China. The endophytic bacterium Brevibacterium halotolerans JZ7 was selected for its strong antagonistic activity and growth-promoting characteristics. Gas-chromatography mass-spectrometry analysis showed that acetoin, 2,3-butanediol and fenretinide were the three dominant volatile organic compounds produced by strain JZ7. Fenretinide strongly suppressed spore germination of F. oxysporum in vitro. Pot experiments showed that strain JZ7 colonized both the roots and rhizosphere soil of Chinese jujube and significantly reduced F. oxysporum level in jujube rhizosphere soil. CONCLUSION: We demonstrated that B. halotolerans JZ7 can be developed into a biological control agent to combat root rot disease of Chinese jujube in the Xinjiang province of China. SIGNIFICANCE AND IMPACT OF THE STUDY: The suggested strategy for biological control of jujube root rot disease is fully in accordance with the current principles of sustainability.

Antibacterial Performance of a Streptomyces spectabilis Strain Producing Metacycloprodigiosin.

After separation of bacterial colonies on solid plates, purification, and screening through the agar cup-plate method, an antibiotic-resistant bacterial isolate was obtained, and named strain L20190601, the 16S rRNA gene sequence data of strain L20190601 to GenBank, NCBI have provided GenBank accession number MW931615. 16S rRNA gene sequencing revealed that this isolate was highly similar to a number of Streptomyces species. Among them, the homology with S. spectabilis was the highest, reaching 99.9, together with curved hyphal morphology and biochemical tests, allowed us to identify strain L20190601 as S. spectabilis. The red pigment produced by S. spectabilis strain L20190601 was structurally identified. An acid-base color reaction assay showed that when this pigment was dissolved in a solution at pH 3.0 and 9.0, the color of the solution was red and yellow, respectively. In addition, the analysis of absorption spectra revealed that at pH 8.0 and 3.0, the maximum absorption peaks were at 466 and 531 nm, respectively. These results are consistent with the spectral absorption characteristics of metacycloprodigiosin reported in the literature. Moreover, the retention time of purified pigments was identical to those of standard metacycloprodigiosin solutions. Mass spectrometry analysis revealed that the molecular weight of the red compound was 392.2 [M + H]+. Finally, metacycloprodigiosin was found to be effective against eight clinically common pathogens: Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Streptococcus pyogenes, Pseudomonas aeruginosa, Bacillus typhi, Candida albicans, and Trichophyton rubrum. In summary, metacycloprodigiosin exhibited strong antibacterial activity and a broad antibacterial spectrum, and thus is a promising compound for the development of a new type of antibacterial drug.

Fungicide Resistance Profiles of Botrytis cinerea Isolates From Michigan Vineyards and Development of a TaqMan Assay for Detection of Fenhexamid Resistance.

Botrytis cinerea on grapes causes bunch rot at both pre- and postharvest stages, in which losses can reach up to 100%. Chemical control primarily relies on the prophylactic use of site-specific fungicides. Repeated applications of these products raise the risk of fungicide resistance development in B. cinerea populations, which can result in disease control failures. To determine the extent of resistance, B. cinerea isolates were collected from grape clusters in the northwest and southwest grape growing regions of Michigan in 2014 and 2018 (n = 115 and 125, respectively). These isolates were phenotyped using discriminatory doses of eight fungicides to determine the levels of resistance. Fungicide resistance increased from 2014 to 2018, mostly affecting the active ingredients fenhexamid, fluopyram, and iprodione. B. cinerea isolates resistant to multiple fungicides were detected in 2014 and 2018, with a higher frequency of resistance in 2018. TaqMan real-time PCR has been developed to detect B. cinerea fungicide resistance to fenhexamid and to differentiate the erg27 F412S/I/V alleles. The TaqMan assay was tested for sensitivity, specificity, and reproducibility on purified DNA and infected grape tissue samples. Our data provide essential information to growers about the efficacy for B. cinerea control using the available botryticides. Furthermore, the developed fenhexamid markers will be transferred to diagnostic clinics to assist growers in the management of bunch rot before resistance-related control failures occur.

[Surgical treatment of Stanford type A aortic dissection after thoracic endovascular aortic repair].

Objective: To examine the surgical treatment of Stanford type A aortic dissection (type A dissection) after thoracic endovascular aortic repair (TEVAR). Methods: The data of 58 patients with reoccurrence of type A dissection after TEVAR admitted into the Department of Cardiovascular Surgery, Henan Chest Hospital from February 2012 to January 2020 were analyzed retrospectively. There were 40 males and 18 females, aged (57.0±6.7) years (range: 31 to 71 years). The time between recurrence of type A dissection and TEVAR (M(QR)) was 37 days (72.8 months) (range: 1 h to 14 years). Forty-eight cases underwent emergency operation, 9 cases underwent sub-emergency operation, and 1 case died of dissection rupture on the way to the operating room. All 57 patients underwent radical treatment. Fifty-four cases underwent the frozen elephant trunk technique under deep hypothermia circulatory arrest and selective cerebral perfusion, and 3 cases (>65 years old) underwent arch debranch anastomosis+ascending aorta replacement+descending arch covered stent implantation under mild hypothermia. Results: The operation time was (445±32) minutes (range: 382 to 485 minutes), the aortic crossclamp time was (103±19) minutes (range: 89 to 133 minutes), the cardiopulmonary bypass time was (189±27) minutes (range: 162 to 221 minutes), and the intraoperative blood loss was (665±343) ml (range: 450 to 1 750 ml). Postoperative ICU stay time was 5 (6) days (range: 2 to 27 days), and postoperative hospital stay was 14.0 (4.5) days (range: 2 to 36 days). Three cases died, including 2 cases with severe brain complications and 1 case with systemic multiple organ failure caused by severe liver insufficiency and gastrointestinal hemorrhage. Postoperative follow-up was 0.5 to 7.0 years, which showed that 1 case had left coronary artery anastomotic stoma fistula 3 months after operation and underwent reoperation, 2 cases underwent thoracoabdominal aortic replacement again, and the rest of patients had no anastomotic stoma fistula and incomplete stent distortion and expansion on CT angiography. Four cases died during follow-up, and 1 case died of sudden cerebral infarction 2 years after operation. Conclusion: The recurrent type A dissection after TEVAR is mostly related to stent graft, and the patients can undergo operation actively with good prognosis.

Application of Chlorophyte ChlB Gene and Cyanophyte NIES Gene in the Detection of Drowning-Related Plankton.

ABSTRACT: Objective To construct a polymerase chain reaction-capillary electrophoresis （PCR-CE） detection method using ChlB gene and NIES gene, investigate the method's specificity and sensitivity, and to evaluate its application value in drowning diagnosis. Methods The specific primers ChlB and NIES were designed for the conserved sequence of chlorophyte ChlB gene and cyanophyte NIES gene in GenBank to construct PCR-CE detection method; 50 species of standard DNA samples were amplified; the sensitivity was determined by gradient concentration detection of positive standard samples; 25 actual cadaver lung tissue samples （drowned： 20, natural death： 5） were detected, and the simultaneous detection results of microwave digestion-vacuum filtration-automated scanning electron microscopy （MD-VF-Auto SEM） were simultaneously compared. Results The minimum DNA detection concentration of primers ChlB and NIES was 0.161 ng and 0.109 ng, respectively, which could specifically amplify chlorophyte （Chlorella pyrenoidosa） and cyanophyte ［Microcystis aeruginosa （producing and not producing toxin）］ widespread in water. The product fragments were 156 bp and 182 bp, respectively. The results of non-drowning tissues were negative. Conclusion This method has high sensitivity and specificity. It can be applied to the detection of plankton related to drowning and combined with MD-VF-Auto SEM method, can increase the detection range of plankton related to drowning and improve the evidence power of drowning diagnosis.

IL-22 relieves sepsis-induced liver injury via activating JAK/STAT3 signaling pathway.

The purpose of this study was to investigate the influence of interleukin(IL)-22 on the Janus kinase/ signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway and sepsis-induced liver injury in rats. A total of 48 Sprague-Dawley rats were randomly divided into sham-operated group (n=12), model group (n=12), low-dose group (n=12) and high-dose group (n=12). Next, rat models of sepsis-induced liver injury were established through cecal ligation and puncture (CLP). At 12 h after surgery, blood was collected by heart puncture to detect liver function of the rats. It was found that the activity of alanine aminotransferase (ALT) and aspartame aminotransferase (AST) and the content of total bilirubin were reduced in low-dose group and high-dose group. Hematoxylin-eosin (HE) staining results revealed that after treatment with IL-22, the liver injury was relieved compared with model group. Moreover, the results of TUNEL staining assay revealed that the apoptosis level of liver cells declined after treatment with IL-22. Enzyme-linked immunosorbent assay (ELISA) results demonstrated that the levels of IL-6 and TNF-α were reduced, while the level of IL-10 was increased after treatment with IL-22. Moreover, it was discovered that the SOD content was overtly elevated in low-dose and high-dose groups compared with that in the model group. Finally, using Western blotting, it was confirmed that in comparison with the model group, the levels of Bcl-2/Bax and JAK/STAT3 signaling pathway-related proteins were markedly raised, while the level of Caspase-3 was decreased in the low-dose and high-dose groups. In conclusion, IL-22 can improve liver function, reduce the apoptosis level of liver cells, the expression of apoptosis-related proteins and the release of inflammatory factors, and alleviate liver injury by activating the JAK/STAT3 signaling pathway.

How does the two-child policy affect the sex ratio at birth in China? A cross-sectional study.

BACKGROUND: The One-Child Policy led to the imbalance of the sex ratio at birth (SRB) in China. After that, Two-Child Policy was introduced and gradually liberalized at three stages. If both the husband and wife of one couple were the only child of their parents, they were allowed to have two children in policy (BTCP). If only one of them was the only child, they were allowed to have two children in policy (OTCP). The Universal Two-Child Policy (UTCP) allowed every couple to have two children. The objective of this study was to explore the changing trend of SRB at the stages of Two-Child Policy, to analyze the effect of population policy on SRB in terms of maternal age, delivery mode, parity, maternal education, delivery hospital, and to figure out what factors have greater impact on the SRB. METHODS: The data of the study came from Hebei Province Maternal Near Miss Surveillance System, covered the parturients delivered at 28 gestation weeks or more in 22 hospitals from January 1, 2013 to December 31, 2017. We compared the SRB at different policy stages, analyzed the relationship between the SRB and population policy by logistic regression analysis. RESULTS: Total 270,878 singleton deliveries were analyzed. The SRB, 1.084 at BTCP, 1.050 at OTCP, 1.047 at UTCP, declined rapidly (χ2 = 15.97, P < 0.01). With the introduction of Two-Child Policy, the percentage of parturients who were 30-34, ≥35 years old rose significantly, and the percentage of multiparous women increased significantly (40.7, 47.2, 56.6%). The neonatal mortality declined significantly (8.4‰, 6.7‰, 5.9‰, χ2 = 44.49, P < 0.01), the mortality rate of female infant gradually declined (48.2, 43.7, 43.9%). The logistic regression analysis showed the SRB was correlated to the three population policy stages in terms of maternal age, delivery mode, parity, maternal education, delivery hospital. CONCLUSIONS: The SRB has declined to normal level with the gradually liberalizing of Two-Child Policy in China. Advanced maternal age, cesarean delivery, multiparous women, middle level education, rural hospital are the main factors of effect on the decline of the SRB.

Health and economic consequences of applying the United States' PM2.5 automobile emission standards to other nations: a case study of France and Italy.

OBJECTIVES: The US has among the world's strictest automobile emission standards, but it is now loosening them. It is unclear where a nation should draw the line between the associated cost burden imposed by regulations and the broader societal benefits associated with having cleaner air. Our study examines the health benefits and cost-effectiveness of introducing stricter vehicle emission standards in France and Italy. STUDY DESIGN: Quasi-experimental study. METHODS: We used cost-effectiveness modeling to measure the incremental quality-adjusted life years (QALYs) and cost (Euros) of adopting more stringent US vehicle emission standards for PM2.5 in France and Italy. RESULTS: Adopting Obama era US vehicle emission standards would likely save money and lives for both the French and Italian populations. In France, adopting US emission standards would save €1000 and increase QALYs by 0.04 per capita. In Italy, the stricter standards would save €3000 and increase QALYs by 0.31. The results remain robust in both the sensitivity analysis and probabilistic Monte Carlo simulation model. CONCLUSIONS: Adopting more stringent emission standards in France and Italy would save money and lives.

Efficacy of Natamycin Against Gray Mold of Stored Mandarin Fruit Caused by Isolates of Botrytis cinerea With Multiple Fungicide Resistance.

Gray mold caused by Botrytis cinerea is an emerging postharvest disease of mandarin fruit in California. Management of postharvest diseases of mandarins relies on postharvest fungicides; however, multiple resistance to fungicides of different modes of action is common in B. cinerea populations from mandarin, leading to their failure to control decay. Natamycin is commonly used in the food industry as an additive, and it has been registered as a biofungicide for postharvest use on citrus and some other fruits. Sensitivity to natamycin of 64 isolates of B. cinerea from decayed mandarin fruit with known resistance phenotypes to other citrus postharvest fungicides (azoxystrobin, fludioxonil, pyrimethanil, and thiabendazole) was tested. Effective concentrations of natamycin to cause a 50% reduction relative to the control for conidial germination were from 0.324 to 0.567 µg/ml (mean of 0.444 µg/ml), and those for mycelial growth were 1.021 to 2.007 µg/ml (mean of 1.578 µg/ml). Minimum inhibitory concentrations where no fungal growth was present were 0.7 to 1.0 µg/ml for conidial germination and 5.0 to 10.0 µg/ml for mycelial growth. No cross-resistance between natamycin and other citrus postharvest fungicides was detected. Decay control efficacy tests with natamycin were conducted on mandarin fruit inoculated with B. cinerea isolates exhibiting five different fungicide resistance phenotypes, and natamycin significantly reduced incidence and lesion size of gray mold on fruit, regardless of fungicide resistance phenotypes. Natamycin has the potential to be an effective tool for integration into postharvest fungicide programs to control gray mold and manage B. cinerea isolates resistant to fungicides with other modes of action.

Simulation-based mastery learning compared to standard education for discussing diagnostic uncertainty with patients in the emergency department: a randomized controlled trial.

BACKGROUND: Diagnostic uncertainty occurs frequently in emergency medical care, with more than one-third of patients leaving the emergency department (ED) without a clear diagnosis. Despite this frequency, ED providers are not adequately trained on how to discuss diagnostic uncertainty with these patients, who often leave the ED confused and concerned. To address this training need, we developed the Uncertainty Communication Education Module (UCEM) to teach physicians how to discuss diagnostic uncertainty. The purpose of the study is to evaluate the effectiveness of the UCEM in improving physician communications. METHODS: The trial is a multicenter, two-arm randomized controlled trial designed to teach communication skills using simulation-based mastery learning (SBML). Resident emergency physicians from two training programs will be randomly assigned to immediate or delayed receipt of the two-part UCEM intervention after completing a baseline standardized patient encounter. The two UCEM components are: 1) a web-based interactive module, and 2) a smart-phone-based game. Both formats teach and reinforce communication skills for patient cases involving diagnostic uncertainty. Following baseline testing, participants in the immediate intervention arm will complete a remote deliberate practice session via a video platform and subsequently return for a second study visit to assess if they have achieved mastery. Participants in the delayed intervention arm will receive access to UCEM and remote deliberate practice after the second study visit. The primary outcome of interest is the proportion of residents in the immediate intervention arm who achieve mastery at the second study visit. DISCUSSION: Patients' understanding of the care they received has implications for care quality, safety, and patient satisfaction, especially when they are discharged without a definitive diagnosis. Developing a patient-centered diagnostic uncertainty communication strategy will improve safety of acute care discharges. Although use of SBML is a resource intensive educational approach, this trial has been deliberately designed to have a low-resource, scalable intervention that would allow for widespread dissemination and uptake. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov (NCT04021771). Registration date: July 16, 2019.