The Influence of Al and Nb on the Low Oxygen Pressure Pre-Oxidation Behavior of Fe-35Ni-20Cr-xAl-yNb Alloys at 1000 °C.

To investigate the impact of Al and Nb elements on the formation of a protective oxide layer on the surface of Fe-35Ni-20Cr-xAl-yNb (x = 0, 2, 4, 6 wt.%; y = 0, 1, 2 wt.%) alloys, their oxidation behavior was examined at 1000 °C, 10-17 atm. and 10-25 atm. oxygen pressure, and the oxidation mechanism was analyzed by Factsage and Pandat calculations. Enhancing the Al content at 10-17 atm. inhibited the generation of FeCr2O4 on the alloy surface and increased the Al content in the M2O3 layer. When the Al content exceeded 6 wt.%, the oxide film partially peeled off. It was found that the addition of Nb increased the activity of Cr and Al and decreased the activity of Ni and Fe and promoted the formation of Al2O3, and the appearance of Nb2O5 in the subsurface layer increased the density of the oxide film. In addition, under an oxygen pressure of 10-25 atm., the only protective layer on the surface of the alloy comprised of Al2O3. The experimental results demonstrated that the Fe-35Ni-20Cr-4Al-2Nb alloy generated a continuous and dense Al2O3 protective film, and the reduction in oxygen pressure and the addition of Nb elements were favorable for selective external oxidation of Al2O3.

Bispectral Index Monitoring in the Nursing of Patients With Paroxysmal Sympathetic Hyperactivity.

AIM: To investigate the clinical nursing effect of bispectral index (BIS) monitoring for paroxysmal sympathetic hyperactivity (PSH) patients in the neurosurgical intensive care unit (NICU). METHODS: From January 2022 to June 2023, a total of 30 patients with PSH secondary to moderate to severe craniocerebral injury in the NICU were monitored for BIS. The patients' paroxysmal sympathetic hyperactivity-assessment measure (PSH-AM) scores were recorded. PSH patients generally appear in 3 states: calm state, seizure state, and postmedication state. Thirty PSH patients' BIS values were recorded during the calm period, during the seizure state, and postmedication state, and these 3 different stages' BIS values were divided into groups A, B, and C, using the Kruskal-Wallis H test to compare groups. RESULTS: The Kruskal-Wallis H test yielded a value of H=22.599, P<0.001. H0 was rejected against the test standard of α=0.05, and the BIS values of groups A, B, and C differed. The BIS values of group A and group B differed after a pairwise comparison, and the difference was statistically significant (adjusted P=0.001). Group B and group C had different BIS values, and the difference was statistically significant (adjusted P=0.001); group A and Group C had no difference in BIS values, and the difference was not statistically significant (adjusted P=1.00). CONCLUSIONS: Taking BIS value as the nursing observation index for PSH patients can make nursing work more objective, reasonable, and accurate, reduce the inducing factors of PSH attack, further reduce the attack of PSH, save nursing resources, and help guide the safety assessment of sedative use.

Report on Pseudoaneurysm Caused by Injury of Internal Carotid Artery During Endoscopic Pituitary Surgery and Rebleeding After Treatment With Willis Covered Stent.

OBJECTIVE: Report on a case of pseudoaneurysm which was caused by injury of the internal carotid artery (ICA) during endoscopic endonasal surgery (EES), which was followed by rebleeding after treatment with a Willis covered stent. METHODS: A woman, aged 68, underwent EES for the treatment of a pituitary adenoma. During the surgery, the right ICA was injured, and successfully hemostasis by packed with cottonoid and gelatin sponge. Besides, cerebral angiography was performed in the interventional operating room for the purpose of discovering the formation of a pseudoaneurysm in the cavernous sinus segment of ICA, which was treated with a covered stent. After successfully placing the covered stent, the patient was promptly transferred to the general operating room for the removal of the cottonoid and to address the bleeding once again. The authors employ crushed muscles and cottonoid to locally compress and stop bleeding. Owing to concerns about the risk of rebleeding in the patient, after stent implantation, the patient did not utilize antiplatelet drugs. After the surgery, the patient developed occlusion of the right ICA and massive cerebral infarction in the right hemisphere. Dehydration, anti-infection, rehabilitation, hyperbaric oxygen, as well as related treatments, were given. The cottonoid was removed in EES 2 months postsurgery, and no instances of bleeding were observed. Six months after surgery, the patient had clear consciousness and hemiplegia in the left limb, with a Glasgow Outcome Scale score of 4. RESULTS: The ICA was injured during EES, which resulted in the formation of a pseudoaneurysm, the Willis stent was adopted for treatment, and there was a risk of rebleeding after the nasal packing (cottonoid, crushed muscles) was removed immediately. CONCLUSIONS: The ICA was injured during EES after bleeding was controlled by packing with cottonoid, crushed muscles, etc, subsequently, the patient was given intravascular treatment, it is advised to make thorough preparations and, after a suitable period, remove nasal packing in the hybrid operating room to address unexpected situations and unforeseen circumstances.

Functional properties and skin care effects of sodium trehalose sulfate.

BACKGROUND: It is known that heparinoid, a mucopolysaccharide polysulfate, is effective in improving rough skin and promoting blood circulation as medicines for diseased areas. However, heparinoid has a molecular weight of more than 5000 and cannot penetrate healthy stratum corneum. OBJECTIVE: We tested the efficacy of sulfated oligosaccharides with a molecular weight of less than 2000 on the human skin barrier function and moisturizing function. METHODS: We measured the transepidermal water loss (TEWL) of a three-dimensional human epidermis model cultured for 3 days after topical application of sulfated oligosaccharides, then observed the effects on TEWL suppression. The mRNA levels of proteins involved in intercellular lipid transport and storage in the stratum corneum, and moisture retention were measured using RT-qPCR. RESULTS: An increase in the mRNA levels of the ATP-binding cassette subfamily A member 12 (ABCA12), which transports lipids into stratum granulosum, was confirmed. Increases were also observed in the mRNA levels of filaggrin (FLG), which is involved in the generation of natural moisturizing factors, and of caspase-14, calpain-1 and bleomycin hydrolase, which are involved in the degradation of FLG. Antibody staining confirmed that the application of sodium trehalose sulfate to 3D model skin resulted in more ABCA12, ceramide, transglutaminase1, and FLG than those in controls. In a randomized, placebo-controlled, double-blind study, participants with low stratum corneum water content applied a lotion and emulsion containing sodium trehalose sulfate to their faces for 4 weeks. Sodium trehalose sulfate decreased the TEWL and increased the stratum corneum water content. CONCLUSION: These results suggest that cosmetics containing sodium trehalose sulfate act on the epidermis by increasing barrier factors and moisturizing factors, thereby ameliorating dry skin.

A hepatic sparganosis misdiagnosed as intrahepatic mass-forming cholangiocarcinoma: a case report and literature review.

Hepatic sparganosis (HS) is extremely rare and has not been previously reported in Eastern China. We report the diagnosis and treatment of a patient with HS from Xuzhou City, Jiangsu Province, China. The patient was admitted due to an acute biliary tract infection, and the symptoms improved after treatment at the Gastroenterology Department. During an ultrasound examination on admission, an abnormal echo was incidentally discovered at the junction of the left and right lobes of the liver. Thereafter, upper abdominal computed tomography (CT) and magnetic resonance imaging (MRI) non-contrast and contrast-enhanced examinations, and serum tumor biomarker examination were completed. After a multidisciplinary treatment (MDT) discussion at the Department of Hepatobiliary Surgery, the patient was diagnosed with intrahepatic mass-type cholangiocarcinoma (IMCC) and surgery was recommended. The patient underwent surgical treatment, and postoperative pathology revealed HS. No signs of intrahepatic recurrence were observed during the 1-year follow-up period.

The mechanism of epigallocatechin-3-gallate inhibiting the antigenicity of ß-lactoglobulin under pH 6.2, 7.4 and 8.2: Multi-spectroscopy and molecular simulation methods.

The antigenicity of ß-lactoglobulin (ß-LG) can be influenced by pH values and reduced by epigallocatechin-3-gallate (EGCG). However, a detailed mechanism concerning EGCG decreasing the antigenicity of ß-LG at different pH levels lacks clarity. Here, we explore the inhibition mechanism of EGCG on the antigenicity of ß-LG at pH 6.2, 7.4 and 8.2 using enzyme-linked immunosorbent assay, multi-spectroscopy, mass spectrometry and molecular simulations. The results of Fourier transform infrared spectroscopy (FTIR) and circular dichroism (CD) elucidate that the noncovalent binding of EGCG with ß-LG induces variations in the secondary structure and conformations of ß-LG. Moreover, EGCG inhibits the antigenicity of ß-LG the most at pH 7.4 (98.30 %), followed by pH 6.2 (73.18 %) and pH 8.2 (36.24 %). The inhibitory difference is attributed to the disparity in the number of epitopes involved in the interacting regions of EGCG and ß-LG. Our findings suggest that manipulating pH conditions may enhance the effectiveness of antigenic inhibitors, with the potential for further application in the food industry.

T-bet Regulates Ion Channels and Transporters and Induces Apoptosis in Intestinal Epithelial Cells.

T-bet, encoded by TBX21, is extensively expressed across various immune cell types, and orchestrates critical functions in their development, survival, and physiological activities. However, the role of T-bet in non-immune compartments, notably the epithelial cells, remains obscure. Herein, a Tet-O-T-bet transgenic mouse strain is generated for doxycycline-inducible T-bet expression in adult animals. Unexpectedly, ubiquitous T-bet overexpression causes acute diarrhea, intestinal damage, and rapid mortality. Cell-type-specific analyses reveal that T-bet-driven pathology is not attributable to its overexpression in CD4+ T cells or myeloid lineages. Instead, inducible T-bet overexpression in the intestinal epithelial cells is the critical determinant of the observed lethal phenotype. Mechanistically, T-bet overexpression modulates ion channel and transporter profiles in gut epithelial cells, triggering profound fluid secretion and subsequent lethal dehydration. Furthermore, ectopic T-bet expression enhances gut epithelial cell apoptosis and markedly suppresses colon cancer development in xenograft models. Collectively, the findings unveil a previously unrecognized role of T-bet in intestinal epithelial cells for inducing apoptosis, diarrhea, and local inflammation, thus implicating its potential as a therapeutic target for the treatment of cancer and inflammatory diseases.

Enantiomeric analysis of γ(δ)-lactones by reversed phase high performance liquid chromatography using amylose tris(5-chloro-2-methylphenylcarbamate) as stationary phase.

A Chiralpak AY-3R column was investigated for analytical enantiomeric separation of twelve racemic γ(δ)-lactones using reversed phase high performance liquid chromatography. Main influence factors, including organic modifier, flow rate and column temperature, were optimized. Five kinds of γ(δ)-lactones were successfully enantioseparated using the established method: γ-nonanolactone, δ-decalactone, δ-undecalactone, δ-dodecalactone and δ-tetradecalactone. Under optimized conditions, enantiomeric peak resolution (Rs) for the five γ(δ)-lactones reached more than 1.09, 1.08, 1.54, 1.43, and 1.11, respectively. Their chromatographic elution behavior was investigated using Van't Hoff equation and Van Deemter equation. It was found that an exothermic process occurred during enantiomeric separation of γ(δ)-lactones using this chromatographic column, and it showed a typical Van Deemter curve. Finally, this method was applied in enantiomeric ratio analysis of γ(δ)-lactones contents for purchased butter samples, and results confirmed the predominant content of the (R)-configuration of δ-dodecalactone in natural animal butter, while in margarine, an equal proportion of (R/S)-configuration of δ-dodecalactone was detected.

Developments and Trends of Nanotechnology Application in Sepsis: A Comprehensive Review Based on Knowledge Visualization Analysis.

Sepsis, a common life-threatening clinical condition, continues to have high morbidity and mortality rates, despite advancements in management. In response, significant research efforts have been directed toward developing effective strategies. Within this scope, nanotechnology has emerged as a particularly promising field, attracting significant interest for its potential to enhance disease diagnosis and treatment. While several reviews have highlighted the use of nanoparticles in sepsis, comprehensive studies that summarize and analyze the hotspots and research trends are lacking. To identify and further promote the development of nanotechnology in sepsis, a bibliometric analysis was conducted on the relevant literature, assessing research trends and hotspots in the application of nanomaterials for sepsis. Next, a comprehensive review of the subjectively recognized research hotspots in sepsis, including nanotechnology-enhanced biosensors and nanoscale imaging for sepsis diagnostics, and nanoplatforms designed for antimicrobial, immunomodulatory, and detoxification strategies in sepsis therapy, is elucidated, while the potential side effects and toxicity risks of these nanomaterials were discussed. Particular attention is given to biomimetic nanoparticles, which mimic the biological functions of source cells like erythrocytes, immune cells, and platelets to evade immune responses and effectively deliver therapeutic agents, demonstrating substantial translational potential. Finally, current challenges and future perspectives of nanotechnology applications in sepsis with a view to maximizing their great potential in the research of translational medicine are also discussed.

Diagnosis and comprehensive treatment of a glucagonoma in a patient with residual intrahepatic metastases postoperatively: A case report and literature review.

Glucagonomas are rare neuroendocrine neoplasms of the pancreas with malignant potential. At present, their epidemiology is not entirely clear, so clinicians are not well versed, lacking any consensus on diagnosis or comprehensive treatment. The present study reports the case of a 32-year-old woman hospitalized for recurrent glossitis, perioral dermatitis and necrolytic migratory erythema (NME) of both lower limbs. Imaging studies revealed a low-density nodule (~2 cm) in the tail of the pancreas, as well as multiple space-occupying hepatic lesions. Surgical intervention was then selected, and distal pancreatectomy, splenectomy and palliative metastasectomies were performed. Tissue examination subsequently confirmed a primary pancreatic neuroendocrine tumor (grade 2), metastatic to the liver. The NME resolved postoperatively, aided by intramuscular injections of long-acting release octreotide (30 mg) every 28 days. A series of three percutaneous ablative treatments (microwave ablation) were also undertaken within a 2-year period, targeting the liver metastases. The present condition of the patient is good, with no cutaneous relapse to date. Palliative metastasectomies, in conjunction with ablative treatments and combination somatostatin analog (SSA) use, are unique aspects of this case that, to the best of our knowledge, have yet to be documented in the literature. Surgical palliation may benefit patients with liver involvement and prolong their survival time. Likewise, ablative treatments and SSA injections delivered together not only address hepatic spread, but also control hormone-related symptoms, having a positive impact on prognosis. As glucagonomas are so rare, there is no real agreement on their management. The present study aims to guide clinical practice by adding further to the available data.

Efficacy and Safety of Covered Stents Versus Bare-Metal Stents for Aortoiliac Occlusive Disease: A Systematic Review and Meta-Analysis.

PURPOSE: This study aimed to assess the efficacy and safety outcome of covered stents (CSs), as compared with bare-metal stents (BMSs), for the treatment of patients with aortoiliac occlusive disease (AIOD). MATERIALS AND METHODS: A systematic literature search was conducted in PubMed, Embase, and Cochrane Library up to August 2023 to identify all studies comparing efficacy and safety outcomes of CSs versus BMSs for treating AIOD. Our outcome was primary patency, secondary patency, technical success, ankle-brachial index (ABI) variation, target lesion revascularization (TLR), limb salvage, complications, and long-term survival. Dichotomous outcomes were pooled as relative risks (RR) or hazard ratio with the 95% confidence interval (CI). Continuous outcomes were pooled as weighted mean differences and 95% CI. Model selection was based on the heterogeneity of the included studies. RESULTS: There were 10 studies (2 randomized controlled trials, 8 retrospective cohort studies), comprising 1676 sample size. Compared with BMSs, CSs use was associated with better primary patency of patients with a Trans-Atlantic Inter-Society Consensus II (TASC) D lesion (RR, 1.15, 95% CI, 1.04 to 1.27, p=0.007), TLR (RR, 0.39, 95% CI, 0.27 to 0.56, p<0.001), technical success (RR, 1.01, 95% CI, 1.00 to 1.02, p=0.010), and long-term survival (RR, 1.06, 95% CI, 1.01 to 1.11, p=0.020). There is no difference between CSs and BMSs regarding primary patency of all patients, secondary patency, variation in ABI, limb salvage, and complications. CONCLUSIONS: Compared with BMSs, CSs used in AIOD was associated with more favorable primary patency in patients with TASC D lesions, TLR, technical success rates, and patient long-term survival. These results provide evidence of the advantages of using CSs for AIOD treatment. Future studies focusing on long-term variations in ABI, primary patency of different degrees of calcification, vascular segments, and TASC classification are warranted. CLINICAL IMPACT: Although several studies evaluated the clinical efficacy of CS in the context of AIOD treatment, the significance and consistency of these findings were not determined to date. We found that CS was used in AIOD associated with better technical success rate, long-term patient survival, lower target lesion revascularization, and higher primary patency of patients with a Trans-Atlantic Inter-Society Consensus II D lesion when compared with BMSs. Our study provides evidence supporting the superiority of CSs over BMSs in the treatment of AIOD, and furnishing clinicians with guidance for treatment decisions.

Difference in muscle metabolism caused by metabolism disorder of rainbow trout liver exposed to ammonia stress.

Ammonia pollution is an important environmental stress factors in water eutrophication. The intrinsic effects of ammonia stress on liver toxicity and muscle quality of rainbow trout were still unclear. In this study, we focused on investigating difference in muscle metabolism caused by metabolism disorder of rainbow trout liver at exposure times of 0, 3, 6, 9 h at 30 mg/L concentrations. Liver transcriptomic analysis revealed that short-term (3 h) ammonia stress inhibited carbohydrate metabolism and glycerophospholipid production but long-term (9 h) ammonia stress inhibited the biosynthesis and degradation of fatty acids, activated pyrimidine metabolism and mismatch repair, lead to DNA strand breakage and cell death, and ultimately caused liver damage. Metabolomic analysis of muscle revealed that ammonia stress promoted the reaction of glutamic acid and ammonia to synthesize glutamine to alleviate ammonia toxicity, and long-term (9 h) ammonia stress inhibited urea cycle, hindering the alleviation of ammonia toxicity. Moreover, it accelerated the consumption of flavor amino acids such as arginine and aspartic acid, and increased the accumulation of bitter substances (xanthine) and odorous substances (histamine). These findings provide valuable insights into the potential risks and hazards of ammonia in eutrophic water bodies subject to rainbow trout.

Inhibition mechanism of crude lipopeptide from Bacillus subtilis against Aeromonas veronii growth, biofilm formation, and spoilage of channel catfish flesh.

Aeromonas veronii is associated with food spoilage and some human diseases, such as diarrhea, gastroenteritis, hemorrhagic septicemia or asymptomatic and even death. This research investigated the mechanism of the growth, biofilm formation, virulence, stress resistance, and spoilage potential of Bacillus subtilis lipopeptide against Aeromonas veronii. Lipopeptides suppressed the transmembrane transport of Aeromonas veronii by changing the cell membrane's permeability, the structure of membrane proteins, and Na+/K+-ATPase. Lipopeptide significantly reduced the activities of succinate dehydrogenase (SDH) and malate dehydrogenase (MDH) by 86.03% and 56.12%, respectively, ultimately slowing Aeromonas veronii growth. Lipopeptides also restrained biofilm formation by inhibiting Aeromonas veronii motivation and extracellular polysaccharide secretion. Lipopeptides downregulated gene transcriptional levels related to the virulence and stress tolerance of Aeromonas veronii. Furthermore, lipopeptides treatment resulted in a considerable decrease in the extracellular protease activity of Aeromonas veronii, which restrained the decomposing of channel catfish flesh. This research provides new insights into lipopeptides for controlling Aeromonas veronii and improving food safety.

Preliminary Efficacy of a Digital Intervention for Adolescent Depression: Randomized Controlled Trial.

BACKGROUND: Adolescent depression is a significant public health concern; however, access to effective mental health care is limited. Digital therapeutics (DTx) can improve access to evidence-based interventions; however, their efficacy in adolescents is sparsely documented. OBJECTIVE: This study aims to examine the efficacy of a mobile app DTx versus an active control as an adjunct treatment for adolescent depression symptoms. METHODS: An internet-based open-label randomized control trial was conducted nationwide with a partial crossover design, and 168 adolescents aged 13 to 21 years with symptoms of depression were recruited between November 2020 and September 2021. Participants were randomized (1:1) to the cognitive behavioral therapy-based treatment app (Spark) or to a psychoeducational control app (control), which they would use for a duration of 5 weeks. The primary outcome was a between-group (Spark vs control) difference in the change in depression symptoms from baseline to postintervention, as measured by the Patient Health Questionnaire-8 (PHQ-8) using a linear mixed-effects analysis. The PHQ-8 ranges from 0 to 24, with scores of 5 to 9 indicating mild depression symptoms, scores of 10 to 14 indicating moderate symptoms, scores of 15 to 19 indicating moderately severe symptoms, and scores of 20 to 24 indicating severe symptoms. A minimal clinically important difference (5-point reduction between baseline and postintervention) in the Spark arm and group differences in remission and treatment response rates based on the PHQ-8 at postintervention were also investigated. RESULTS: A total of 160 participants were randomized, 80 in the Spark arm (mean age 16.89, SD 2.5 y) and 80 in the control arm (mean age 16.79, SD 2.59 y). Data from 121 participants (Spark: n=63; control: n=58) with moderate to severe (PHQ-8≥10) symptoms at baseline were included in the primary analyses following a modified intention-to-treat principle. A linear mixed-effect analysis revealed a nonsignificant difference between the study arms in depression symptom change over the intervention period. The Spark arm met a minimal clinically important difference threshold (mean -5.08, 95% CI -6.72 to -3.42). The remission rate in the Spark arm was significantly higher than that in the control arm (11/63, 17% vs 2/58, 3%; χ21=6.2; P=.01; false discovery rate-adjusted P=.03). The treatment response rates were not significantly different between the study arms (P=.07; false discovery rate-adjusted P=.16). Post hoc analyses including participants with mild to severe (PHQ-8 score ≥5) symptoms at baseline revealed promising evidence that Spark is effective in those with mild to severe symptoms. CONCLUSIONS: There is initial evidence that a self-guided, cognitive behavioral therapy-based DTx intervention may effectively treat mild to severe depression symptoms in adolescents. DTx may improve access to mental health care for adolescents or serve as an important adjunct to the standard of care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04524598; https://clinicaltrials.gov/study/NCT04524598.

Long-term abacus training gains in children are predicted by medial temporal lobe anatomy and circuitry.

Abacus-based mental calculation (AMC) is a widely used educational tool for enhancing math learning, offering an accessible and cost-effective method for classroom implementation. Despite its universal appeal, the neurocognitive mechanisms that drive the efficacy of AMC training remain poorly understood. Notably, although abacus training relies heavily on the rapid recall of number positions and sequences, the role of memory systems in driving long-term AMC learning remains unknown. Here, we sought to address this gap by investigating the role of the medial temporal lobe (MTL) memory system in predicting long-term AMC training gains in second-grade children, who were longitudinally assessed up to fifth grade. Leveraging multimodal neuroimaging data, we tested the hypothesis that MTL systems, known for their involvement in associative memory, are instrumental in facilitating AMC-induced improvements in math skills. We found that gray matter volume in bilateral MTL, along with functional connectivity between the MTL and frontal and ventral temporal-occipital cortices, significantly predicted learning gains. Intriguingly, greater gray matter volume but weaker connectivity of the posterior parietal cortex predicted better learning outcomes, offering a more nuanced view of brain systems at play in AMC training. Our findings not only underscore the critical role of the MTL memory system in AMC training but also illuminate the neurobiological factors contributing to individual differences in cognitive skill acquisition. RESEARCH HIGHLIGHTS: We investigated the role of medial temporal lobe (MTL) memory system in driving children's math learning following abacus-based mental calculation (AMC) training. AMC training improved math skills in elementary school children across their second and fifth grade. MTL structural integrity and functional connectivity with prefrontal and ventral temporal-occipital cortices predicted long-term AMC training-related gains.

Impact of C-reactive protein on the effect of Roxadustat for the treatment of anemia in chronic kidney disease: a systematic review of randomized controlled trials.

BACKGROUND: Chronic inflammation, reflected by an increased blood C-reactive protein (CRP) level, is common in patients with chronic kidney disease (CKD) and is involved in the development of renal anemia. This systematic review aims to investigate the impacts of CRP on the efficacy of hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) in the treatment of renal anemia in patients with CKD. METHODS: We conducted a comprehensive search of electronic databases including Pubmed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang, and the International Clinical Trials Registry Platform (ICTRP), from their inception to May 19, 2022. We systematically reviewed evidence from randomized controlled trials using HIF-PHIs for renal anemia treatment. The mean difference (MD) in changes in hemoglobin concentration (∆Hb) before and after treatment served as the meta-analysis outcome, utilizing a random-effects model. We compared groups with CRP levels greater than or equal to the upper limit of normal (ULN) and less than the ULN. Additionally, further analysis was conducted in the CRP ≥ ULN group comparing HIF-PHIs and erythropoiesis-stimulating agents (ESA). RESULTS: A total of 7 studies from 6 publications were included in the analysis. In the comparison between the CRP ≥ ULN group and the CRP < ULN group, 524 patients from 4 studies were incorporated into the analysis. All patients received roxadustat as the primary intervention. The pooled results revealed no significant difference in ΔHb between patients with CRP ≥ ULN and CRP < ULN at baseline (Mean Difference: 0.00, 95% Confidence Interval: -0.32 to 0.33, P = 0.99). Moreover, within the CRP ≥ ULN group, three studies involving 1399 patients compared the efficacy of roxadustat and erythropoiesis-stimulating agents (ESAs). The results indicated no significant difference in ΔHb between patients treated with ESAs and HIF-PHIs (Mean Difference: 0.24, 95% Confidence Interval: -0.08 to 0.56, P = 0.14). In terms of medication dosage, an increase in ESA dose over time was observed across various studies, particularly evident in the CRP ≥ ULN group, while the dose of roxadustat remains constant over time and is not influenced by the baseline levels of CRP. CONCLUSIONS: Our systematic review demonstrates that roxadustat exhibits similar efficacy across different CRP levels. Moreover, within the CRP ≥ ULN group, roxadustat can maintain efficacy comparable to ESA without the necessity for dose escalation. TRIAL REGISTRATION: CRD42023396704.

Insight into the high-temperature oxidation kinetics of acetylene: A first-principles molecular dynamics study.

The study on high-temperature oxidation kinetics and kinetic modeling of acetylene (C2H2) has significant importance for its engineering applications. In this paper, the first-principles molecular dynamics method is used to simulate the C2H2 oxidation under high temperatures for the first time. Our results show that there are 38 intermediates and 225 elementary reactions in the process of C2H2 oxidation. The formation mechanisms of "prompt" CO2, as well as gas pollutants CHOCHO and HCOOH are revealed in depth. Four intermediates, CHCHO, CHOCO, CHOCHO and HCOOH, which have significant controversy in current kinetic models, are verified. And a new intermediate, CHOCO2, is discovered. Meanwhile, our simulation also shows that radicals, such as HO2, OH, O, etc. play a key role in promoting the oxidation of intermediates in the early stage of C2H2 oxidation. Combined with quantum chemical calculations, a detailed chemical kinetic model of C2H2/air (FP-C2H2) is built and verified by simulating ignition delay time, species concentration in the flow reactor and premixed laminar flame speed. Our studies provide novel insight for understanding the complex chemical reaction kinetics, and environmental and human health threats from air pollutant formation during C2H2 combustion.

Oxidative stress resistance prompts pyrroloquinoline quinone biosynthesis in Hyphomicrobium denitrificans H4-45.

Pyrroloquinoline quinone (PQQ) is a natural antioxidant with diverse applications in food and pharmaceutical industries. A lot of effort has been devoted toward the discovery of PQQ high-producing microbial species and characterization of biosynthesis, but it is still challenging to achieve a high PQQ yield. In this study, a combined strategy of random mutagenesis and adaptive laboratory evolution (ALE) with fermentation optimization was applied to improve PQQ production in Hyphomicrobium denitrificans H4-45. A mutant strain AE-9 was obtained after nearly 400 generations of UV-LiCl mutagenesis, followed by an ALE process, which was conducted with a consecutive increase of oxidative stress generated by kanamycin, sodium sulfide, and potassium tellurite. In the flask culture condition, the PQQ production in mutant strain AE-9 had an 80.4% increase, and the cell density increased by 14.9% when compared with that of the initial strain H4-45. Moreover, batch and fed-batch fermentation processes were optimized to further improve PQQ production by pH control strategy, methanol and H2O2 feed flow, and segmented fermentation process. Finally, the highest PQQ production and productivity of the mutant strain AE-9 reached 307 mg/L and 4.26 mg/L/h in a 3.7-L bioreactor, respectively. Whole genome sequencing analysis showed that genetic mutations in the ftfL gene and thiC gene might contribute to improving PQQ production by enhancing methanol consumption and cell growth in the AE-9 strain. Our study provided a systematic strategy to obtain a PQQ high-producing mutant strain and achieve high production of PQQ in fermentation. These practical methods could be applicable to improve the production of other antioxidant compounds with uncleared regulation mechanisms. KEY POINTS: • Improvement of PQQ production by UV-LiCl mutagenesis combined with adaptive laboratory evolution (ALE) and fermentation optimization. • A consecutive increase of oxidative stress could be used as the antagonistic factor for ALE to enhance PQQ production. • Mutations in the ftfL gene and thiC gene indicated that PQQ production might be increased by enhancing methanol consumption and cell growth.