A Cost-Effective Sulfide Solid Electrolyte Li7P3S7.5O3.5 with Low Density and Excellent Anode Compatibility.

The commercialization of all-solid-state Li batteries (ASSLBs) demands solid electrolytes with strong cost-competitiveness, low density (for enabling satisfactory energy densities), and decent anode compatibility (the need for cathode compatibility can be circumvented by the cathode coating techniques that are widely applied in sulfide-based ASSLBs). However, none of the reported oxide, sulfide, or chloride solid electrolytes meets these requirements simultaneously. Here, we design a Li7P3S7.5O3.5 (LPSO) solid electrolyte, which shows a combination of all the aforementioned characteristics. The synthesis of this material does not need the expensive Li2S, so the raw materials cost is only $14.42/kg, which, unlike most solid electrolytes, lies below the $50/kg threshold for commercialization. The density of LPSO is 1.70 g cm-3, considerably lower than those of the oxide (typically above 5 g cm-3) and chloride (around 2.5 g cm-3) solid electrolytes. Besides, LPSO also shows excellent anode compatibility. The Li | LPSO | Li cell cycles stably with a potential of ~50 mV under 0.1 mA cm-2 for over 4200 h at 25 °C, and the all-solid-state pouch cell with the Si anode shows a capacity retention of 89.29% after 200 cycles under 88.6 mA g-1 at 60 °C.

Epidemiological and etiological characteristics of 1266 patients with severe acute respiratory infection in central China, 2018-2020: a retrospective survey.

BACKGROUND: Severe acute respiratory infection (SARI), a significant global health concern, imposes a substantial disease burden. In China, there is inadequate data concerning the monitoring of respiratory pathogens, particularly bacteria, among patients with SARI. Therefore, this study aims to delineate the demographic, epidemiological, and aetiological characteristics of hospitalised SARI patients in Central China between 2018 and 2020. METHODS: Eligible patients with SARI admitted to the First Affiliated Hospital of Zhengzhou University between 1 January 2018 and 31 December 2020 were included in this retrospective study. Within the first 24 h of admission, respiratory (including sputum, nasal/throat swabs, bronchoalveolar lavage fluid, thoracocentesis fluid, etc.), urine, and peripheral blood specimens were collected for viral and bacterial testing. A multiplex real-time polymerase chain reaction (PCR) diagnostic approach was used to identify human influenza virus, respiratory syncytial virus, parainfluenza virus, adenovirus, human bocavirus, human coronavirus, human metapneumovirus, and rhinovirus. Bacterial cultures of respiratory specimens were performed with a particular focus on pathogenic microorganisms, including S. pneumoniae, S. aureus, K. pneumoniae, P. aeruginosa, Strep A, H. influenzae, A. baumannii, and E. coli. In cases where bacterial culture results were negative, nucleic acid extraction was performed for PCR to assay for the above-mentioned eight bacteria, as well as L. pneumophila and M. pneumoniae. Additionally, urine specimens were exclusively used to detect Legionella antigens. Furthermore, epidemiological, demographic, and clinical data were obtained from electronic medical records. RESULTS: The study encompassed 1266 patients, with a mean age of 54 years, among whom 61.6% (780/1266) were males, 61.4% (778/1266) were farmers, and 88.8% (1124/1266) sought medical treatment in 2020. Moreover, 80.3% (1017/1266) were housed in general wards. The most common respiratory symptoms included fever (86.8%, 1122/1266) and cough (77.8%, 986/1266). Chest imaging anomalies were detected in 62.6% (792/1266) of cases, and 58.1% (736/1266) exhibited at least one respiratory pathogen, with 28.5% (361/1266) having multiple infections. Additionally, 95.7% (1212/1266) of the patients were from Henan Province, with the highest proportion (38.3%, 486/1266) falling in the 61-80 years age bracket, predominantly (79.8%, 1010/1266) seeking medical aid in summer and autumn. Bacterial detection rate (39.0%, 495/1266) was higher than viral detection rate (36.9%, 468/1266), with the primary pathogens being influenza virus (13.8%, 175/1266), K. pneumoniae (10.0%, 127/1266), S. pneumoniae (10.0%, 127/1266), adenovirus (8.2%, 105/1266), P. aeruginosa (8.2%, 105/1266), M. pneumoniae (7.8%, 100/1266), and respiratory syncytial virus (7.7%, 98/1266). During spring and winter, there was a significant prevalence of influenza virus and human coronavirus, contrasting with the dominance of parainfluenza viruses in summer and autumn. Respiratory syncytial virus and rhinovirus exhibited higher prevalence across spring, summer, and winter. P. aeruginosa, K. pneumoniae, and M. pneumoniae were identified at similar rates throughout all seasons without distinct spikes in prevalence. However, S. pneumoniae showed a distinctive pattern with a prevalence that doubled during summer and winter. Moreover, the positive detection rates of various other viruses and bacteria were lower, displaying a comparatively erratic prevalence trend. Among patients admitted to the intensive care unit, the predominant nosocomial bacteria were K. pneumoniae (17.2%, 43/249), A. baumannii (13.6%, 34/249), and P. aeruginosa (12.4%, 31/249). Conversely, in patients from general wards, predominant pathogens included influenza virus (14.8%, 151/1017), S. pneumoniae (10.4%, 106/1017), and adenovirus (9.3%, 95/1017). Additionally, paediatric patients exhibited significantly higher positive detection rates for influenza virus (23.9%, 11/46) and M. pneumoniae (32.6%, 15/46) compared to adults and the elderly. Furthermore, adenovirus (10.0%, 67/669) and rhinovirus (6.4%, 43/669) were the primary pathogens in adults, while K. pneumoniae (11.8%, 65/551) and A. baumannii (7.1%, 39/551) prevailed among the elderly, indicating significant differences among the three age groups. DISCUSSION: In Central China, among patients with SARI, the prevailing viruses included influenza virus, adenovirus, and respiratory syncytial virus. Among bacteria, K. pneumoniae, S. pneumoniae, P. aeruginosa, and M. pneumoniae were frequently identified, with multiple infections being very common. Additionally, there were substantial variations in the pathogen spectrum compositions concerning wards and age groups among patients. Consequently, this study holds promise in offering insights to the government for developing strategies aimed at preventing and managing respiratory infectious diseases effectively.

Alternate Crystal Structure Achieving Ionic Conductivity above 1 mS cm-1 in Cost-Effective Zr-Based Chloride Solid Electrolytes.

The realization of practical, commercial all-solid-state Li batteries requires the solid electrolyte to possess not only high ionic conductivity (above 1 mS cm-1 at 25 °C) but also low cost (below $50/kg). Unlike most of the present solid electrolytes, the recently reported Zr-based chloride solid electrolytes generally cost less than $50/kg, but their ionic conductivities at 25 °C are below 1 mS cm-1. Here, a Li-ion conductivity of 1.35 mS cm-1 at 25 °C and an estimated material cost of $11.09/kg are achieved simultaneously in a Li3Zr0.75OCl4 solid electrolyte. Unlike other Zr-based chloride systems, Li3Zr0.75OCl4 does not exhibit the trigonal structure, but is isostructural with Li3ScCl6, whose monoclinic structure allows for much faster ion transport. With such desirable characteristics, the all-solid-state cell formed by LiNi0.8Mn0.1Co0.1O2 and Li3Zr0.75OCl4 shows a capacity retention above 80.9% for 700 cycles at 25 °C and 5 C (975 mA g-1).

A cost-effective, ionically conductive and compressible oxychloride solid-state electrolyte for stable all-solid-state lithium-based batteries.

To enable the development of all-solid-state batteries, an inorganic solid-state electrolyte should demonstrate high ionic conductivity (i.e., > 1 mS cm-1 at 25 °C), compressibility (e.g., > 90% density under 250-350 MPa), and cost-effectiveness (e.g., < $50/kg). Here we report the development and preparation of Li1.75ZrCl4.75O0.5 oxychloride solid-state electrolyte that demonstrates an ionic conductivity of 2.42 mS cm-1 at 25 °C, a compressibility enabling 94.2% density under 300 MPa and an estimated raw materials cost of $11.60/kg. As proof of concept, the Li1.75ZrCl4.75O0.5 is tested in combination with a LiNi0.8Mn0.1Co0.1O2-based positive electrode and a Li6PS5Cl-coated Li-In negative electrode in lab-scale cell configuration. This all-solid-state cell delivers a discharge capacity retention of 70.34% (final discharge capacity of 70.2 mAh g-1) after 2082 cycles at 1 A g-1, 25 °C and 1.5 tons of stacking pressure.

Etiology of lower respiratory tract in pneumonia based on metagenomic next-generation sequencing: a retrospective study.

Introduction: Pneumonia are the leading cause of death worldwide, and antibiotic treatment remains fundamental. However, conventional sputum smears or cultures are still inefficient for obtaining pathogenic microorganisms.Metagenomic next-generation sequencing (mNGS) has shown great value in nucleic acid detection, however, the NGS results for lower respiratory tract microorganisms are still poorly studied. Methods: This study dealt with investigating the efficacy of mNGS in detecting pathogens in the lower respiratory tract of patients with pulmonary infections. A total of 112 patients admitted at the First Affiliated Hospital of Zhengzhou University between April 30, 2018, and June 30, 2020, were enrolled in this retrospective study. The bronchoalveolar lavage fluid (BALF) was obtained from lower respiratory tract from each patient. Routine methods (bacterial smear and culture) and mNGS were employed for the identification of pathogenic microorganisms in BALF. Results: The average patient age was 53.0 years, with 94.6% (106/112) obtaining pathogenic microorganism results. The total mNGS detection rate of pathogenic microorganisms significantly surpassed conventional methods (93.7% vs. 32.1%, P < 0.05). Notably, 75% of patients (84/112) were found to have bacteria by mNGS, but only 28.6% (32/112) were found to have bacteria by conventional approaches. The most commonly detected bacteria included Acinetobacter baumannii (19.6%), Klebsiella pneumoniae (17.9%), Pseudomonas aeruginosa (14.3%), Staphylococcus faecium (12.5%), Enterococcus faecium (12.5%), and Haemophilus parainfluenzae (11.6%). In 29.5% (33/112) of patients, fungi were identified using mNGS, including 23 cases of Candida albicans (20.5%), 18 of Pneumocystis carinii (16.1%), and 10 of Aspergillus (8.9%). However, only 7.1 % (8/112) of individuals were found to have fungi when conventional procedures were used. The mNGS detection rate of viruses was significantly higher than the conventional method rate (43.8% vs. 0.9%, P < 0.05). The most commonly detected viruses included Epstein-Barr virus (15.2%), cytomegalovirus (13.4%), circovirus (8.9%), human coronavirus (4.5%), and rhinovirus (4.5%). Only 29.4% (33/112) of patients were positive, whereas 5.4% (6/112) of patients were negative for both detection methods as shown by Kappa analysis, indicating poor consistency between the two methods (P = 0.340; Kappa analysis). Conclusion: Significant benefits of mNGS have been shown in the detection of pathogenic microorganisms in patients with pulmonary infection. For those with suboptimal therapeutic responses, mNGS can provide an etiological basis, aiding in precise anti-infective treatment.

A Simple Nomogram for Predicting Osteoarthritis Severity in Patients with Knee Osteoarthritis.

Objective: To explore the influencing factors of knee osteoarthritis (KOA) severity and establish a KOA nomogram model. Methods: Inpatient data collected in the Department of Joint Surgery, Chengde Medical University Affiliated Hospital from January 2020 to January 2022 were used as the training cohort. Patients with knee osteoarthritis who were admitted to the Third Hospital of Hebei Medical University from February 2022 to May 2022 were taken as the external validation group of the model. In the training group, the least absolute shrinkage and selection operator (LASSO) method was used to screen the factors of KOA severity to determine the best prediction index. Then, after combining the significant factors from the LASSO and multivariate logistic regressions, a prediction model was established. All potential prediction factors were included in the KOA severity prediction model, and the corresponding nomogram was drawn. The consistency index (C-index), area under the receiver operating characteristic (ROC) curve (AUC), GiViTi calibration band, net classification improvement (NRI) index, and integrated discrimination improvement (IDI) index evaluation of a model predicted KOA severity. Decision curve analysis (DCA) and clinical influence curves were used to study the model's potential clinical value. The validation group also used the above evaluation indexes to measure the diagnostic efficiency of the model. Spearman correlation was used to investigate the relationship between nomogram-related markers and osteoarthritis severity. Results: The total sample included 572 patients with knee osteoarthritis, including 400 patients in the training cohort and 172 patients in the validation cohort. The nomogram's predictive factors were age, pulse, absolute value of lymphocytes, mean corpuscular haemoglobin concentration (MCHC), and blood urea nitrogen (BUN). The C-index and AUC of the model were 0.802. The GiViTi calibration band (P = 0.065), NRI (0.091), and IDI (0.033) showed that the modified model can distinguish between severe KOA and nonsevere KOA. DCA showed that the KOA severity nomogram has clinical application value with threshold probabilities between 0.01 and 0.78. The external verification results also show the stability and diagnosis of the model. Age, pulse, MCHC, and BUN are correlated with osteoarthritis severity. Conclusions: A nomogram model for predicting KOA severity was established for the first time that can visually identify patients with severe KOA and is novel for indirectly evaluating KOA severity by nonimaging means.

Alleviation of iron deficiency in pear by ammonium nitrate and nitric oxide.

BACKGROUND: Iron is essential for the growth and development of trace elements in plants, and iron deficiency can lead to leaf chlorosis. Ammonium and nitrate are the major forms of nitrogen present in soils. Ammonium nitrate alleviates the chlorosis of leaves caused by iron deficiency, but the mechanism is not clear in pear. RESULTS: Ammonium nitrate induced the increase of nitric oxide (NO) under iron deficiency. We further analyzed the effect of NO by exogenous NO treatment. The results showed that ammonium nitrate and NO increased the activity of ferric chelate reductase. NO induced the expression of multiple IRT genes and promoted the transmembrane transport of irons. Ammonium nitrate and NO promoted the activity of nitrogen assimilation-related enzymes and the nitrogen absorption capacity, and they also increased glutamine synthetase activity. Finally, ammonium nitrate and NO increased chlorophyll synthesis, with subsequent increase in the photosynthetic capacity of plants and accumulation of biomass. CONCLUSION: Ammonium nitrate indirectly alleviates the symptoms of plant yellowing by promoting the increase of NO, which increases the response of iron transporters. Both substances increase the nitrogen accumulation in plants. This study demonstrates a new option for minimizing Fe deficiency by regulating the balance between nutrients.

Upregulated YB-1 protein promotes glioblastoma growth through a YB-1/CCT4/mLST8/mTOR pathway.

Y-box-binding protein 1 (YB-1) is a multifunctional RNA binding protein involved in virtually every step of RNA metabolism. However, the functions and mechanisms of YB-1 in one of the most aggressive cancers, glioblastoma, are not well understood. In this study, we found that YB-1 protein was markedly overexpressed in glioblastoma and acted as a critical activator of both mTORC1 and mTORC2 signaling. Mechanistically, YB-1 bound the 5'UTR of CCT4 mRNA to promote the translation of CCT4, a component of the CCT chaperone complex, that in turn activated the mTOR signaling pathway by promoting mLST8 folding. In addition, YB-1 autoregulated its own translation by binding to its 5'UTR, leading to sustained activation of mTOR signaling. In patients with glioblastoma, high protein expression of YB-1 correlated with increased expression of CCT4 and mLST8 and activated mTOR signaling. Importantly, the administration of RNA decoys specifically targeting YB-1 in a mouse xenograft model resulted in slower tumor growth and better survival. Taken together, these findings uncover a disrupted proteostasis pathway involving a YB-1/CCT4/mLST8/mTOR axis in promoting glioblastoma growth, suggesting that YB-1 is a potential therapeutic target for the treatment of glioblastoma.

Effects of whole-body vibration plus hip-knee muscle strengthening training on adult patellofemoral pain syndrome: a randomized controlled trial.

PURPOSE: To investigate whether whole-body vibration (WBV) plus hip-knee muscle strengthening is more efficient in relieving pain and improving function than hip-knee strengthening alone. METHODS: Thirty-six participants with patellofemoral pain syndrome (PFPS) were recruited and randomly allocated to either the (1) hip-knee strengthening only (HK group, n = 18) or (2) WBV plus hip-knee strengthening group (WHK group, n = 18). All participants attended 18 physiotherapy sessions (3 sessions/week, 40 min/session) over 6 weeks. Data on symptoms, function, surface electromyography (sEMG) signals from the vastus medialis and gluteus medius, and quality of life were evaluated at baseline (T0), 6 weeks after (T6), and the 12-week follow-up (T18). RESULTS: Significant group × time interactions were found for the VAS score (p < 0.001) and vastus medialis performance (p ≤ 0.015). The WHK group exhibited a greater pain relief than did the HK group at T18 (p ≤ 0.014). The WHK group exhibited significantly larger improvements in the RMS value than did the HK group at T6 (p ≤ 0.011). CONCLUSIONS: The present study shows that 6 weeks of WBV plus hip-knee strengthening can improve vastus medialis performance and maintain long-term pain relief to a significantly greater extent than can hip-knee strengthening alone.IMPLICATIONS FOR REHABILITATIONThe present study shows that 6 weeks of WBV plus hip-knee strengthening can improve vastus medialis performance and maintain long-term pain relief to a significantly greater extent than can hip-knee strengthening alone.

A Fluoride-Ion-Conducting Solid Electrolyte with Both High Conductivity and Excellent Electrochemical Stability.

Solid-state fluoride-ion batteries (FIBs) circumvent multiple formidable bottlenecks of lithium-ion batteries, but their overall performance remains inferior due to the absence of appropriate solid electrolytes. Presently the conductivity of most solid electrolytes for FIBs is too low to enable room-temperature cycling, while the few sufficiently conductive ones only allow for very low discharge voltages because of the narrow electrochemical stability window (ESW). Here, high room-temperature conductivity and a decent ESW are simultaneously achieved by designing a solid electrolyte CsPb0.9 K0.1 F2.9 . Its room-temperature conductivity is 1.23 × 10-3  S cm-1 , comparable to the most conductive system reported so far (PbSnF4 , 5.44 × 10-4 -1.6 × 10-3  S cm-1 ), but the ESW is several times broader. With these appealing characteristics simultaneously achieved in the solid electrolyte, a cell with much higher voltages than other room-temperature-operable solid-state FIBs in literature is successfully constructed, and stably cycled at 25 °C for 4581 h without considerable capacity fade.

A cost-effective and humidity-tolerant chloride solid electrolyte for lithium batteries.

Li-ion-conducting chloride solid electrolytes receive considerable attention due to their physicochemical characteristics such as high ionic conductivity, deformability and oxidative stability. However, the raw materials are expensive, and large-scale use of this class of inorganic superionic conductors seems unlikely. Here, a cost-effective chloride solid electrolyte, Li2ZrCl6, is reported. Its raw materials are several orders of magnitude cheaper than those for the state-of-the-art chloride solid electrolytes, but high ionic conductivity (0.81 mS cm-1 at room temperature), deformability, and compatibility with 4V-class cathodes are still simultaneously achieved in Li2ZrCl6. Moreover, Li2ZrCl6 demonstrates a humidity tolerance with no sign of moisture uptake or conductivity degradation after exposure to an atmosphere with 5% relative humidity. By combining Li2ZrCl6 with the Li-In anode and the single-crystal LiNi0.8Mn0.1Co0.1O2 cathode, we report a room-temperature all-solid-state cell with a stable specific capacity of about 150 mAh g-1 for 200 cycles at 200 mA g-1.

QKI-5 regulates the alternative splicing of cytoskeletal gene ADD3 in lung cancer.

Accumulating evidence indicates that the alternative splicing program undergoes extensive changes during cancer development and progression. The RNA-binding protein QKI-5 is frequently downregulated and exhibits anti-tumor activity in lung cancer. Howeve-r, little is known about the functional targets and regulatory mechanism of QKI-5. Here, we report that upregulation of exon 14 inclusion of cytoskeletal gene Adducin 3 (ADD3) significantly correlates with a poor prognosis in lung cancer. QKI-5 inhibits cell proliferation and migration in part through suppressing the splicing of ADD3 exon 14. Through genome-wide mapping of QKI-5 binding sites in vivo at nucleotide resolution by iCLIP-seq analysis, we found that QKI-5 regulates alternative splicing of its target mRNAs in a binding position-dependent manner. By binding to multiple sites in an upstream intron region, QKI-5 represses the splicing of ADD3 exon 14. We also identified several QKI mutations in tumors, which cause dysregulation of the splicing of QKI targets ADD3 and NUMB. Taken together, our results reveal that QKI-mediated alternative splicing of ADD3 is a key lung cancer-associated splicing event, which underlies in part the tumor suppressor function of QKI.

Productive transcription of miR-124-3p by RelA and RNA polymerase II directs RIP1 ubiquitination-dependent apoptosis resistance during hypoxia.

The K63-linked ubiquitination of RIP1 coordinates survival/death homeostasis by driving transcription of genes downstream of RelA. Previously, we demonstrated that EGF-dependent RelA transactivation overcomes hypoxia-initiated apoptosis, yet the underlying mechanisms remain mysterious. We report here that UBXN1 deficiency empowers apoptosis resistance against hypoxia through triggering IκBα degradation, for which K63-linked ubiquitination of RIP1 is required. MiR-124-3p is a bona fide inhibitor upstream of UBXN1, thereby antagonizing the hypoxia-initiated apoptosis. UBXN1 repression by miR-124-3p restores the K63-linked ubiquitination of RIP1, IKKß phosphorylation, IκBα-RelA disassembly, RelA nuclear localization and transactivation of EGF gene as well as EGF secretion under hypoxia. Reconstitution of wild-type UBXN1, but not a truncated UBXN1ΔUBA mutant, or pharmacological inhibition of RelA transactivation in miR-124-3p-replete cells compromises the apoptosis-resistant phenotypes of miR-124-3p. Hypoxia transcriptionally downregulates miR-124-3p by disassociating RelA and RNAP II from its promoter. EGFR activation renders the K63-linked ubiquitination of RIP1 and hypoxic tolerance in conjunction with miR-124-3p. Our findings identify a pivotal role of miR-124-3p in ubiquitin conjugation of RIP1 against hypoxic damage and underscore that productive transcription of miR-124-3p by RelA and RNAP II might be a switching mechanism for this process.

[Correlation between shock index and severity of septic shock and its prognostic value].

OBJECTIVE: To discuss the correlation between shock index (SI) and severity and the values to forecast the prognosis in patients with septic shock. METHODS: 127 patients with septic shock admitted to intensive care unit (ICU) of Zhejiang Provincial People's Hospital from January 1st, 2016 to October 31st, 2017 were enrolled, and they were divided into survival group and death group according to the outcomes after 28-day hospitalized. The vital signs, laboratory indexes, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), lactate clearance rate (LCR) of 3 hours after fluid resuscitation, and shock index on admission (SI1) and shock index of 3 hours after fluid resuscitation (SI2) were compared between the two groups. The correlation among SI and APACHE II, SOFA, LCR was analyzed. The receiver operating characteristic curve (ROC) was drawn to evaluate the prognostic value of SI in patients with septic shock. RESULTS: A total of 127 patients were included, 52 in survival group (40.9%) and 75 in death group (59.1%). The SI1, SI2, APACHE II and SOFA in the death group were significantly higher than those in the survival group (SI1: 1.62±0.46 vs. 1.35±0.32, SI2: 1.36±0.24 vs. 0.93±0.15, APACHE II: 17.5±4.0 vs. 13.6±3.5,SOFA: 9.5±2.3 vs. 6.3±1.5), and LCR was significantly lower than that in the survival group [(14.4±5.2)% vs. (28.6±8.6)%], with statistically significant differences (all P < 0.01). The correlation analysis showed that SI1 was significantly positively correlated with APACHE II (r = 0.458, P = 0.000) and SOFA (r = 0.535, P = 0.000), SI2 was also significantly positively correlated with APACHE II (r = 0.624, P = 0.000) and SOFA (r = 0.656, P = 0.000), while SI1 and SI2 were significantly negatively correlated with LCR (r values were -0.348, -0.435, both P = 0.000), and the SI2 were more remarkable. ROC curve analysis showed that the area under ROC curve (AUC) of SI1 for predicting the prognosis of septic shock was 0.720 [95% confidence interval (95%CI) = 0.620-0.831, P < 0.05]; when SI1 = 1.68, the sensitivity, specificity, Yoden index, positive predictive value and negative predictive value were 79.5%, 65.6%, 0.451, 0.759 and 0.636, respectively. The AUC of the SI2 to predict prognosis of septic shock was 0.826 (95%CI = 0.739-0.826, P < 0.05); when SI2 = 1.37, the sensitivity, specificity, Yoden index, positive predictive value and negative predictive value were 85.7%, 87.6%, 0.733, 0.893 and 0.902, respectively. CONCLUSIONS: Compared with SI1, SI2 was more correlated with the severity in patients with septic shock and it had more values to predict prognosis.

Inorganic sulfur and mercury speciation in the water level fluctuation zone of the Three Gorges Reservoir, China: The role of inorganic reduced sulfur on mercury methylation.

The water level fluctuation zone (WLFZ) of the Three Gorges Reservoir (TGR) in China is a unique geomorphological unit that undergoes annual flooding and drying alternation cycle. The alternating redox conditions within the WLFZ are expected to result in dynamic cycling of reduced sulfur species, which could affect mercury (Hg) methylation due to the high affinity of reduced sulfur species to both inorganic divalent mercury (Hg(II)i) and methylmercury (MeHg). Variations of inorganic sulfur species (measured as acid volatile sulfide, chromium reductive sulfur, elemental sulfur, and water-soluble sulfate), total mercury (THg) and MeHg were studied at two typical WLFZ sites in the TGR from July 2015 to June 2016. Whereas the water-soluble sulfate contents stayed essentially constant, the reduced inorganic sulfur contents varied greatly as the water level changed. Compared with the control soils, the MeHg contents in the WLFZ soils increased, suggesting that water level fluctuations accelerated the methylation process of Hg(II)i. In situ Hg(II)i-methylation also appeared to occur in the sub-layer of the drained sediment during the draw-down season. The significant correlation between MeHg and elemental sulfur (S(0)) further suggests that polysulfides may have played a role in Hg(II)i-methylation by increasing the bioavailable Hg(II)i content in the WLFZ of the TGR.

Transcriptional downregulation of microRNA-19a by ROS production and NF-κB deactivation governs resistance to oxidative stress-initiated apoptosis.

Cell apoptosis is one of the main pathological alterations during oxidative stress (OS) injury. Previously, we corroborated that nuclear factor-κB (NF-κB) transactivation confers apoptosis resistance against OS in mammalian cells, yet the underlying mechanisms remain enigmatic. Here we report that microRNA-19a (miR-19a) transcriptionally regulated by reactive oxygen species (ROS) production and NF-κB deactivation prevents OS-initiated cell apoptosis through cylindromatosis (CYLD) repression. CYLD contributes to OS-initiated cell apoptosis, for which NF-κB deactivation is essential. MiR-19a directly represses CYLD via targeting 3' UTR of CYLD, thereby antagonizing OS-initiated apoptosis. CYLD repression by miR-19a restores the IKKß phosphorylation, RelA disassociation from IκBα, IκBα polyubiquitination and degradation, RelA recruitment at VEGF gene promoter as well as VEGF secretion in the context of OS. Either pharmacological deactivation of NF-κB or genetic upregulation of CYLD compromises the apoptosis-resistant phenotypes of miR-19a. Furthermore, miR-19a is transcriptionally downregulated upon OS in two distinct processes that require ROS production and NF-κB deactivation. VEGF potentiates the ability of miR-19a to activate NF-κB and render apoptosis resistance. Our findings underscore a putative mechanism whereby CYLD repression-mediated and NF-κB transactivation-dependent miR-19a regulatory feedback loop prevents cell apoptosis in response to OS microenvironment.

A Functional Polymorphism (rs10817938) in the XPA Promoter Region Is Associated with Poor Prognosis of Oral Squamous Cell Carcinoma in a Chinese Han Population.

Single nucleotide polymorphisms of XPA gene have been studied in several cancers such as rs10817938, rs2808668. However, the role of XPA polymorphisms in patients with oral squamous cell carcinoma (OSCC) remains unclear. Thus, we analyzed the association of XPA polymorphisms with OSCC risk, clinicopathological characteristics and prognosis in the present study. TaqMan genotyping was used to evaluate the frequency of rs10817938, rs2808668 polymorphisms in OSCC patients. The prognostic significance of these polymorphisms was evaluated using Kaplan-Meier curves, Log-Rank analyses, and the Cox proportional hazard model. Luciferase reporter assay, RT-PCR and western blot were used to determine whether rs10817938 could influence transcription activity and XPA expression. The results showed that individuals carrying TC and CC genotypes had significantly greater risk of developing OSCC (OR = 1.42, 95% CI 1.04-1.93; OR = 2.75, 95% CI 1.32-5.71, respectively) when compared with wild-type TT genotype at rs10817938. OSCC patients with C allele at rs10817938 were more susceptible to lymph metastases, poor pathological differentiation and late TNM stage (OR = 1.67, 95% CI 1.17-2.37; OR = 1.64, 95% CI 1.18-2.28; OR = 1.54, 95% CI 1.11-2.14; respectively). A significant gene-environment interaction between smoking and CC genotype at rs10817938 was observed (COR = 3.60, 95% CI 1.20-10.9) and data also showed that OSCC patients with CC genotype and C allele had worse survival (p<0.001 for both). The T to C substitution at rs10817938 significantly decreased transcription activity of XPA gene, XPA mRNA and protein were also decreased in individuals with C allele at rs10817938. In addition, no significant association of rs2808668 polymorphism with OSCC risk, prognosis could be observed. In conclusion, the present study showed that XPA rs10817938 polymorphism is a functional SNP in vitro and in vivo and a biomarker for poor prognosis in OSCC patients.

[Observation on the best dose of methylprednisolone improving lung injury in swine with paraquat intoxication].

OBJECTIVE: To observe the best dose of methylprednisolone improving lung injury in swine with paraquat intoxication. METHODS: Acute lung injury (ALI/ARDS) model was made by an intraperitoneal injection of a large dose of 20%PQ solution20 millilitres in swine. Then 24 swine were randomly divided into 4 groups: exposed PQ control group, 5 mg/kg of methylprednisolone group, 15 mg/kg of methylprednisolone group, 30 mg/kg of methylprednisolone group. All groups were based on the conventional rehydration for intervention, Arterial blood samples were collected before modeling and 0, 12, 24, 36 hours after different processing for blood gas analysis. At the same time heart rate (HR), mean arterial pressure (MAP), extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) were measured by using PICCO (pulse indicator continuous cardiac output), lung tissue was obtained by punctureneedle to produce lung biopsy, then observe the pathological changes of lung tissue in the microscope. RESULTS: 1. Comparison between groups: there is no significant difference about extravascular lung water index (EVLWI) and semi-quantitative score of lung tissue pathology in four groups (P > 0.05) before modeling, so is t0, there is significant difference at about extravascular lung water index and semi-quantitative score of lung tissue pathology 12 h, 24 h and 36 h after different processing (P < 0.05). Within the group: EVLWI and semi-quantitative score of Lung tissue pathology in four groups significantly increased when the model was made (P < 0.05), after different processing, EVLWI and semi-quantitative score of Lung tissue pathology in exposed PQ control group kept going up, in other three groups, EVLWI and semi-quantitative score of lung tissue pathology went down first and then went up, there is significant difference compared with t0 (P < 0.05). 2. Comparison between groups: there is no significant difference about oxygenation index in four groups (P > 0.05) before modeling, so is t0, there is significant difference about oxygenation at 12 h, 24 h and 36 h after different processing (P < 0.05). Within the group: oxygenation index in four groups significantly decreased when the model was made (P < 0.05), after different processing, oxygenation index in exposed PQ control group kept going down, in other three groups, it showed a downward trend after the first rise, there is significant difference compared with t0 (P < 0.05). 3. After medication for 36h, correlation analysis showed that EVLWI were negatively associated with oxygenation index (r = -0.427, P = 0.022) and positively associated with semi-quantitative score of Lung tissue pathology (r = 0.903, P = 0.034). CONCLUSION: Methylprednisolone can obviously relieve lung injury caused by paraquat poisoning and improve oxygenation. After the model was made, within 24 hours, 30 mg/kg of methylprednisolone have advantage for the PQ poisoning swine, but 15mg/kg of methylprednisolone is best for improving lung injury induced by paraquat intoxication within 24 hours to 36 hours.

Effects of different tidal volume ventilation on paraquat-induced acute lung injury in piglets.

BACKGROUND: The aim of this study was to explore the effects of different tidal volume (VT) ventilation on paraquat-induced acute lung injury or acute respiratory distress syndrome (ALI/ARDS) in piglets. MATERIAL AND METHODS: We developed ALI/ARDS models in piglets by intraperitoneal injection of paraquat (PQ). The piglets were randomly divided into three groups: small VT group (VT=6 ml/kg, n=6), middle VT group (VT=10 ml/kg, n=6), and large VT group (VT=15 ml/kg, n=6), with the positive end-expiratory pressure (PEEP) set as 10 cmH2O. The hemodynamics were monitored by pulse-indicated continuous cardiac output (PiCCO) and the airway pressure changes and blood gas analysis indexes were recorded at different time points. The pathological changes were observed by lung puncture. RESULTS: The piglets showed ALI/ARDS in 4.5±0.8 hours after PQ intraperitoneal injection. PH, PaO2 and oxygenation indexes in the three groups all decreased after modeling success compared with baseline, and PaCO2 increased significantly. PH in the small VT group decreased most obviously after ventilation for 6 hours. PaO2 and oxygenation indexes in the small VT group showed the most obvious increase after ventilation for 2 hours and were much higher than the other two groups after ventilation for 6 hours. PaCO2 increased gradually after mechanical ventilation and the small VT group showed most obvious increase. The ELWI increased obviously after ventilation for 2 hours and then the small VT group clearly decreased. PIP and plateau pressure (Pplat) in the small VT group decreased gradually and in the middle and large VT group they increased after ventilation. The lung histopathology showed that the large VT group had the most severe damage and the small VT group had only minimal damage. CONCLUSIONS: Small tidal volume ventilation combined with PEEP could alleviate the acute lung injury induced by paraquat and improve oxygenation.

[Reproduction of acute lung injury model induced by paraquat in piglet].

OBJECTIVE: To reproduce acute lung injury (ALI) model induced by paraquat (PQ) in piglet. METHODS: Ten healthy female piglets were divided into control group (n=4) and the experimental group (n=6) in accordance with the random number table. The experimental group was given intraperitoneal injection of 20% PQ (20 mL) to reproduce the model of ALI, while the control group was given the same amount of normal saline. All piglets were dynamically monitored with pulse-indicated continuous cardiac output (PiCCO) for heart rate (HR), mean arterial pressure (MAP), extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI). Changes in arterial blood pH, oxygen partial pressure (PaO2), partial pressure of carbon dioxide (PaCO2), oxygenation index (PaO2/FiO2), peak inspiratory pressure (PIP) and platform of the airway pressure (Pplat) were recorded until the PaO2/FiO2 ≤ 300 mmHg. Pathological changes in lung tissue under microscopy were observed. RESULTS: Model of ALI induced by PQ was successfully reproduced in the experimental group in 5 piglets. The average time of successful reproduction was (4.5 ± 0.2) hours. The HR, MAP, EVLWI, PVPI, PIP and Pplat of the experimental group were increased gradually after PQ intraperitoneal injection, and all indices were significantly higher than those in control group when the model was successfully reproduced (HR: 132.0 ± 6.9 bpm vs. 113.0 ± 3.4 bpm, t=-21.632, P=0.000; MAP: 114.0 ± 6.0 mmHg vs. 98.0 ± 3.5 mmHg, t=-18.217, P=0.000; EVLWI: 19.2 ± 2.8 mL/kg vs. 12.5 ± 1.2 mL/kg, t=-76.283, P=0.000; PVPI: 5.9 ± 1.3 vs. 3.1 ± 0.4, t=-31.879, P=0.000; PIP: 25.4 ± 2.5 cmH2O vs. 18.6 ± 1.5 cmH2O, t=-77.421, P=0.000; Pplat: 19.6 ± 2.2 cmH2O vs. 13.5 ± 1.7 cmH2O, t=-69.452, P=0.000). The pH value, PaO2 and PaO2/FiO2 declined gradually while the PaCO2 elevated gradually in experimental group after PQ intraperitoneal injection, the differences between the two groups were statistically significant (pH value: 7.35 ± 0.04 vs. 7.43 ± 0.05, t=9.108, P=0.000; PaO2: 82.0 ± 7.4 mmHg vs. 172.0 ± 11.6 mmHg, t=102.470, P=0.000; PaCO2: 44.0 ± 4.0 mmHg vs. 35.0 ± 2.0 mmHg, t=-10.217, P=0.000; PaO2/FiO2: 273.0 ± 14.8 mmHg vs. 573.0 ± 22.5 mmHg, t=341.565, P=0.000). Obvious damage of pulmonary tissue was shown when the model was reproduced. CONCLUSIONS: By intraperitoneal injections of 20% PQ 20 mL, a stable PQ-induced ALI model can be reproduced in piglets.