Correction: Land reclamation pattern and environmental regulation guidelines for port clusters in the Bohai Sea, China.

[This corrects the article DOI: 10.1371/journal.pone.0259516.].

Effect of Akson Therapy on Acoustic Parameters in Patients with Functional Dysphonia.

OBJECTIVE: Functional dysphonia can impair the language expression ability and adversely affect the career development of some patients. Therefore, an active exploration of effective treatment options is imperative. This study investigated the effect of Akson therapy on acoustic parameters in patients with functional dysphonia. MATERIALS AND METHODS: In this retrospective analysis, 79 patients with functional dysphonia who received conventional voice correction training from June 2020 to June 2021 were included in the reference group (RG). Our hospital has implemented Akson therapy since July 2021. Correspondingly, 72 patients with functional dysphonia who underwent Akson therapy from July 2021 to July 2022 were enrolled in the observation group (OG). The acoustic parameters such as fundamental frequency (F0), jitter, shimmer, and normalized noise energy (NNE); the aerodynamic parameters including maximum phonation time (MPT), mean airflow rate (MFR), and Voice Handicap Index-10 (VHI-10) score; and the Grade, Roughness, Breathiness, Asthenia, and Strain scale (GRBAS) score were measured before and after treatment and compared between the two groups. RESULTS: The F0, jitter, shimmer, NNE, MPT, and MFR values as well as the VHI-10 score and the grade (G), roughness (R), and breathiness (B) scores on the GRBAS did not significantly differ between the two groups before treatment (P > 0.05). However, significantly lower F0, jitter, shimmer, NNE, and MFR values and higher MPT levels were found in the OG compared to the RG after treatment (P < 0.001). Furthermore, the VHI-10 score and the G, R, and B scores were significantly lower in the OG than in the RG after treatment (P < 0.001), whereas the asthenia (A) and strain (S) scores remained at 0 before and after treatment. CONCLUSION: Akson therapy can improve the acoustic parameters of patients with functional dysphonia to a certain extent, indicating its potential application value.

DEVELOPMENT AND INTERNAL-EXTERNAL VALIDATION OF THE ACCI-SOFA MODEL FOR PREDICTING IN-HOSPITAL MORTALITY OF PATIENTS WITH SEPSIS-3 IN THE ICU: A MULTICENTER RETROSPECTIVE COHORT STUDY.

ABSTRACT: Objective: To achieve a better prediction of in-hospital mortality, the Sequential Organ Failure Assessment (SOFA) score needs to be adjusted and combined with comorbidities. This study aims to enhance the prediction of SOFA score for in-hospital mortality in patients with Sepsis-3. Methods: This study adjusted the maximum SOFA score within the first 3 days (Max Day3 SOFA) in relation to in-hospital mortality using logistic regression and incorporated the age-adjusted Charlson Comorbidity Index (aCCI) as a continuous variable to build the age-adjusted Charlson Comorbidity Index-Sequential Organ Failure Assessment (aCCI-SOFA) model. The outcome was in-hospital mortality. We developed, internally validated, and externally validated the aCCI-SOFA model using cohorts of Sepsis-3 patients from the MIMIC-IV, MIMIC-III (CareVue), and the FAHWMU cohort. The predictive performance of the model was assessed through discrimination and calibration, which was assessed using the area under the receiver operating characteristic and calibration curves, respectively. The overall predictive effect was evaluated using the Brier score. Measurements and main results: Compared with the Max Day3 SOFA, the aCCI-SOFA model showed significant improvement in area under the receiver operating characteristic with all cohorts: development cohort (0.81 vs 0.75, P < 0.001), internal validation cohort (0.81 vs 0.76, P < 0.001), MIMIC-III (CareVue) cohort (0.75 vs 0.68, P < 0.001), and FAHWMU cohort (0.72 vs 0.67, P = 0.001). In sensitivity analysis, it was suggested that the application of aCCI-SOFA in early nonseptic shock patients had greater clinical value, with significant differences compared with the original SOFA scores in all cohorts ( P < 0.05). Conclusion: For septic patients in intensive care unit, the aCCI-SOFA model exhibited superior predictive performance. The application of aCCI-SOFA in early nonseptic shock patients had greater clinical value.

Echinacoside Exerts Antihepatic Fibrosis Effects in High-Fat Mice Model by Modulating the ACVR2A-Smad Pathway.

SCOPE: Nonalcoholic steatohepatitis (NASH) is an increasingly common chronic liver disease in which hepatic fibrosis is the major pathological change. The transforming growth factor ß (TGF-ß)/mall mothers against decapentaplegic (Smad) signaling is the main effector of fibrosis. Although the antifibrotic effect of echinacoside (Ech) on the liver has been indicated previously, the cellular and molecular mechanisms remain unclear. This study aims to investigate both in vivo and in vitro antifibrotic properties of Ech. METHODS AND RESULTS: Cell viability and scratch/wound assays show that Ech significantly inhibits the proliferation, migration, and activation of human hepatic stellate LX-2 cells. In mice with high-fat diet-induced hepatic fibrosis, Ech treatment attenuates the progression of liver injury, inflammation, and fibrosis. Furthermore, transcriptome analysis and subsequent functional validation demonstrate that Ech achieves antifibrotic effects by the activin receptor type-2A (ACVR2A)-mediated TGF-ß1/Smad signaling pathway; ultimately, ACVR2A is demonstrated to be an important target for hepatic fibrosis by inhibiting and inducing the expression of ACVR2A in LX-2 cells. CONCLUSION: Ech exerts potent antifibrotic effects by inhibiting the ACVR2A-mediated TGF-ß1/Smad signaling axis and may serve as an alternative treatment for hepatic fibrosis.

Association between triglyceride-glucose index and in-hospital mortality in critically ill patients with sepsis: analysis of the MIMIC-IV database.

BACKGROUND: This study aimed to explore the association between the triglyceride-glucose (TyG) index and the risk of in-hospital mortality in critically ill patients with sepsis. METHODS: This was a retrospective observational cohort study and data were obtained from the Medical Information Mart for Intensive Care-IV (MIMIC IV2.2) database. The participants were grouped into three groups according to the TyG index tertiles. The primary outcome was in-hospital all-cause mortality. Multivariable logistics proportional regression analysis and restricted cubic spline regression was used to evaluate the association between the TyG index and in-hospital mortality in patients with sepsis. In sensitivity analysis, the feature importance of the TyG index was initially determined using machine learning algorithms and subgroup analysis based on different subgroups was also performed. RESULTS: 1,257 patients (56.88% men) were included in the study. The in-hospital, 28-day and intensive care unit (ICU) mortality were 21.40%, 26.17%, and 15.43% respectively. Multivariate logistics regression analysis showed that the TyG index was independently associated with an elevated risk of in-hospital mortality (OR 1.440 [95% CI 1.106-1.875]; P = 0.00673), 28-day mortality (OR 1.391; [95% CI 1.52-1.678]; P = 0.01414) and ICU mortality (OR 1.597; [95% CI 1.188-2.147]; P = 0.00266). The restricted cubic spline regression model revealed that the risks of in-hospital, 28-day, and ICU mortality increased linearly with increasing TyG index. Sensitivity analysis indicate that the effect size and direction in different subgroups are consistent, the results is stability. Additionally, the machine learning results suggest that TyG index is an important feature for the outcomes of sepsis. CONCLUSION: Our study indicates that a high TyG index is associated with an increased in-hospital mortality in critically ill sepsis patients. Larger prospective studies are required to confirm these findings.

Insight into the molecular mechanism of phosphine toxicity provided by functional analysis of cytochrome b5 fatty acid desaturase and dihydrolipoamide dehydrogenase in the red flour beetle, Tribolium castaneum.

Phosphine is the dominant chemical used in postharvest pest control. Widespread and highly frequent use of phosphine has been selected for pest insects, including Tribolium castaneum, which is highly resistant. Lipid peroxidation and reactive oxygen species (ROS) are two major factors determining phosphine toxicity; however, the mechanisms of production of these two factors in phosphine toxicity are still unknown. Here, we first determined the time course of phosphine-induced lipid peroxidation and ROS production in T. castaneum. Our results showed that lipid peroxidation occurs before ROS in the process of phosphine toxicity, and fumigated beetles with higher resistance levels were associated with weaker activity on lipid peroxidation and ROS. A significant decline in lipid peroxidation was observed in fumigated individuals after knockdown of cytochrome b5 fatty acid desaturase (Cyt-b5-r) via RNA interference (RNAi), indicating that Cyt-b5-r is critical for triggering phosphine-induced lipid peroxidation. Moreover, significant decreases in both ROS and mortality were detected in fumigated T. castaneum adults fed melatonin for 7 days, an inhibitor of lipid peroxidation. Cyt-b5-r RNAi also inhibited ROS production and mortality in phosphine-treated beetles. Meanwhile, a significant decrease in ROS production (68.4%) was detected in dihydrolipoamide dehydrogenase (DLD) knockdown individuals with phenotypes susceptible to phosphine, suggesting that lipid peroxidation initiates ROS with the expression of DLD. However, a significant increase in ROS (122.1%) was detected in the DLD knockdown beetles with strongly resistant phenotypes, indicating that the DLD-involved pathway may not be the only mechanism of ROS generation in phosphine toxicity and the existence of a moonlighting role in downregulating ROS in strongly resistant T. castaneum.

Synergetic roadmap of carbon neutrality and clean air for China.

It is well recognized that carbon dioxide and air pollutants share similar emission sources so that synergetic policies on climate change mitigation and air pollution control can lead to remarkable co-benefits on greenhouse gas reduction, air quality improvement, and improved health. In the context of carbon peak, carbon neutrality, and clean air policies, this perspective tracks and analyzes the process of the synergetic governance of air pollution and climate change in China by developing and monitoring 18 indicators. The 18 indicators cover the following five aspects: air pollution and associated weather-climate conditions, progress in structural transition, sources, inks, and mitigation pathway of atmospheric composition, health impacts and benefits of coordinated control, and synergetic governance system and practices. By tracking the progress in each indicator, this perspective presents the major accomplishment of coordinated control, identifies the emerging challenges toward the synergetic governance, and provides policy recommendations for designing a synergetic roadmap of Carbon Neutrality and Clean Air for China.

YY1-induced LncRNA-TUG1 elevates YOD1 to promote cell proliferation and inhibit bortezomib sensitivity in multiple myeloma.

Taurine upregulated gene 1 (TUG1) has been implicated in the onset and progression of various malignancies. The current study aimed to evaluate the biological function and potential mechanisms of TUG1 in multiple myeloma (MM) progression. TUG1 knockdown in MM cells was investigated in vitro and in vivo to evaluate the role of TUG1. We also predicted the transcription factor (TF) that bound to TUG1 together with the downstream target genes of the TUG1-TF interaction, and evaluated the regulatory mechanism of TUG1 in cell assays. TUG1 knockdown reduced the cell's proliferative and migratory capabilities while increasing apoptosis and bortezomib sensitivity in vitro and inhibiting tumorigenesis in vivo. TUG1 was found in the nucleus of MM cells and was found to be positively regulated by the TF-YY1. Further in vitro mechanistic investigations indicated that the YY1-TUG1 complex targeted YOD1 to regulate MM progression.

A novel drainage strategy using chest tube plus pleural catheter in uniportal upper lobectomy: A randomized controlled trial.

BACKGROUND: In this study we explored whether one pleural catheter plus single chest tube drainage could achieve a noninferior drainage effect when compared with the traditional two chest tubes in uniportal video-assisted thoracoscopic surgery (VATS) for an upper pulmonary lobectomy. METHODS: Patients that underwent an upper pulmonary lobectomy from January to November 2020 were enrolled in this single-center, randomized, open-label, noninferiority trial. Prior to closure, patients were randomized to an intervention group who received an improved drainage strategy involving one pleural catheter with one chest tube (24 Fr), while traditional double chest tube drainage was applied for the control group. RESULTS: A total of 390 patients entered the study, although 190 were excluded for changing nonuniportal surgical approaches or opting for nonlobectomy resections. Finally, 200 patients were randomized (100 in the intervention group and 100 in the control group). The baseline demographic and clinical characteristics were comparable between the groups. The incidence of pneumothorax in the intervention and control groups was similar on postoperative Day 1 (noninferiority, 10% vs. 13%, p = 0.658). In addition, there were no significant differences in secondary outcomes such as incidence of pneumothorax by Day 30, postoperative chest tube/pleural catheter removal time, amount of drainage on Day 1, total amount of drainage after operation, or postoperative hospitalization. A significantly lower pain score was observed in the intervention group (3.33 ± 0.68 vs. 3.68 ± 0.94, p = 0.003). CONCLUSIONS: The new strategy is noninferior to double chest tube drainage after an upper pulmonary lobectomy offers superior pain control, and is recommended for an upper lobectomy by uniportal VATS.

Single-Metal-Encapsulated Double-Cage [Pt@Sn17 ]4- : An Exception from Group 14 Endohedral Clusters.

Group 14 endohedral clusters containing a metal center inside usually possess a single cage topological structure, but here an unexpected single-metal-filled double-cage cluster, [Pt@Sn17 ]4- (1 a) is reported. It can be seen as a combination of the more extended Pt-filled [Pt@Sn9 ] cage and hollow [Sn9 ] cage sharing a central Sn atom, which is offset from the central position. This double-cage species represents the largest group 14 intermetalloid cluster encapsulating a single transition metal atom. DFT calculations show that the capsule-like architecture of [Sn17 ]4- , similar to that found in [Pt2 @Sn17 ]4- , is unstable if filled with a single Pt atom and collapses to the title cluster 1 a upon geometry optimization. Deviation of the central Sn atom occurs due to the vibronic coupling as a consequence of pseudo-Jahn-Teller distortion leading to the bent Cs -symmetrical structure, in contrast to the more symmetrical D2d cage previously reported in [Ni2 @Sn17 ]4- .

Elevated urbanization-driven plant accumulation and human intake risks of polycyclic aromatic hydrocarbons in crops of peri-urban farmlands.

As an ubiquitous carcinogen, polycyclic aromatic hydrocarbons (PAHs) are closely related to anthropogenic activities. The process of urbanization leads to the spatial interlacing of farmlands and urbanized zones. However, field evidence on the influence of urbanization on the accumulation of PAHs in crops of peri-urban farmlands is lacking. This study comparatively investigated the urbanization-driven levels, compositions, and sources of PAHs in 120 paired plant and soil samples collected from the Yangtze River Delta in China and their species-specific human intake risks. The concentrations of PAHs in crops and soils in the peri-urban areas were 2407.92 ng g-1 and 546.64 ng g-1, respectively, which are significantly higher than those in the rural areas. The PAHs in the root were highly relevant to those in the soils (R2 = 0.63, p < 0.01), and the root bioconcentration factors were higher than 1.0, implying the contributions of root uptake to plant accumulations. However, the translocation factors in the peri-urban areas (1.57 ± 0.33) were higher than those in the rural areas (1.19 ± 0.14), indicating the enhanced influence through gaseous absorption. For the congeners, the 2- to 3-ring PAHs showed a higher plant accumulation potential than the 4- to 6-ring PAHs. Principal component analysis show that the PAHs in the peri-urban plants predominantly resulted from urbanization parameters, such as coal combustion, vehicle emissions, and biomass burning. The mean values of estimated dietary intake of PAHs from the consumption of peri-urban and rural crops were 9116 ng day-1 and 6601.83 ng day-1, respectively. The intake risks of different crops followed the order rice > cabbage > carrot > pea. Given the significant input of PAHs from urban to farmland, the influence of many anthropogenic pollutants arising from rapid urbanization should be considered when assessing the agricultural food safety.

Symmetry collapse due to the presence of multiple local aromaticity in Ge244.

Understanding the structural changes taking place during the assembly of single atoms leading to the formation of atomic clusters and bulk materials remains challenging. The isolation and theoretical characterization of medium-sized clusters can shed light on the processes that occur during the transition to a solid-state structure. In this work, we synthesize and isolate a continuous 24-atom cluster Ge244-, which is characterized by X-ray diffraction analysis and Energy-dispersive X-ray spectroscopy, showing an elongated structural characteristic. Theoretical analysis reveals that electron delocalization plays a vital role in the formation and stabilization of the prolate cluster. In contrast with carbon atoms, 4 s orbitals of Ge-atoms do not easily hybridize with 4p orbitals and s-type lone-pairs can be localized with high occupancy. Thus, there are not enough electrons to form a stable symmetrical fullerene-like structure such as C24 fullerene. Three aromatic units with two [Ge9] and one [Ge6] species, connected by classical 2c-2e Ge-Ge σ-bonds, are aligned together forming three independent shielding cones and eventually causing a collapse of the global symmetry of the Ge244- cluster.

[Co2@(Ge17Ni)]4-: the first edge-sharing double-cage endohedral germanide.

We report here a new double-cage endohedral Ge cluster, [Co2@(Ge17Ni)]4-, fused through two [Co@(Ge9Ni)] moieties with a shared Ni-Ge edge. This ternary Co-Ge-Ni species not only represents the first double-cage example of an 18-vertex Zintl cluster, but also fills in the missing link of the edge fusion model in the double-cage systems.

Elastase Inhibitor Cyclotheonellazole A: Total Synthesis and In Vivo Biological Evaluation for Acute Lung Injury.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one of the most common complications in COVID-19. Elastase has been recognized as an important target to prevent ALI/ARDS in the patient of COVID-19. Cyclotheonellazole A (CTL-A) is a natural macrocyclic peptide reported to be a potent elastase inhibitor. Herein, we completed the first total synthesis of CTL-A in 24 linear steps. The key reactions include three-component MAC reactions and two late-stage oxidations. We also provided seven CTL-A analogues and elucidated preliminary structure-activity relationships. The in vivo ALI mouse model further suggested that CTL-A alleviated acute lung injury with reductions in lung edema and pathological deterioration, which is better than sivelestat, one approved elastase inhibitor. The activity of CTL-A against elastase, along with its cellular safety and well-established synthetic route, warrants further investigation of CTL-A as a candidate against COVID-19 pathogeneses.

4-Methylumbelliferone fused oxazole thioether derivatives: synthesis, characterization and antifungal activities.

Series of thioether derivatives containing 4-methylumbelliferone fused oxazole moiety were designed and synthesised, their structures were fully characterized by 1H NMR, 13C NMR and HR-ESI-MS as well. Moreover, the in vitro antifungal potency of the title compounds were preliminarily evaluated for their possible use as a fungicide. Meanwhile, ethyl thioethers 3aa and 3ba displayed remarkable inhibitory effect against the mycelium growth of Valsa mali and Botrytis cinerea with EC50 of 12-16 µg/mL. Furthermore, compounds 3aa and 3ba also exhibited > 88% protective and curative effect against B. cinerea on tomato fruits at 90 µg/mL. Additionally, the environmental toxicity of the title compounds against the brine shrimp Artemia salina were evaluated as well. The results indicated that most of the title compounds exhibited weak toxic to aquatic organism A. salina.

Land reclamation pattern and environmental regulation guidelines for port clusters in the Bohai Sea, China.

Coastal land reclamation (CLR), particularly port reclamation, is a common approach to alleviating land shortages. However, the spatial extent, percentages, and processes of these newly reclaimed ports are largely unknown. The Bohai Sea is the most concentrated area of port reclamation worldwide. Thus, this study addresses the changes in the different coastline types and port reclamation process in the area. The reclamation area of the 13 ports in the Bohai Sea in 2002-2018 was 2,300 km2, which decreased the area of the sea by 3%. The natural coastline length in Tianjin decreased by 47.5 km, whereas the artificial coastline length increased by 46.6 km. Based on the port boundary, however, only 26.3% of the reclaimed areas have been used for port construction, which concentrates in the Tianjin and Tangshan ports. The ratio of built-up area within the ports is only 32.5%, and approximately 48.3% of the reclaimed areas have no construction projects. The port land reclamation in the Bohai Sea has been undergoing periods of acceleration, peak, deceleration, and stagnation since 2002. Hence, future port reclamation should not be totally prohibited, and fine management should be conducted based on the optimization of the reclaimed port area. The innovation of this research is its analysis of the port internal land use pattern, the percentage of built-up area in the ports, and the sustainability of port reclamation policies. The findings have vital implications for scientifically regulating the spatial pattern and exploring the utility of port reclamation.

Air quality improvement via modal shift: Assessment of rail-water-port integrated system planning in Shenzhen, China.

The escalating concerns regarding air pollution problems surrounding port cities have attracted much research attention. The Port of Shenzhen is one of the busiest container ports worldwide, only third to Shanghai and Singapore globally. However, 70% of the freight transportation demand is satisfied via on-road trucks, leading to serious traffic congestion, road accidents and air pollution issues in the city of Shenzhen. This study aims to assess the environmental benefits of modal shift of port-connecting freight transportation by increasing the use of rail and waterborne systems in Shenzhen. To evaluate the environmental benefits of the multimodal transportation strategy in 2025, we employed traffic datasets with a high spatial resolution and a transportation demand model to establish emission inventories and applied them in air quality simulations. Our results indicate that the implementation of multimodal transportation systems could notably reduce the truck volume along major freight corridors, except for roads adjacent to the planned inland ports. The freight traffic activities along the major freight corridors are reduced by nearly 70% over the original freight volume, resulting in a drastic reduction in the emission intensity. Under the most progressive policy-enhanced strategy (PPP) scenario, the total well-to-wheel (WTW) NOX, fine particulate matter (PM2.5) and CO2 emissions could be reduced by 8881 t, 104.8 t and 688 × 103 t, respectively. The NO2 concentration in traffic-intensive areas could be reduced by 5 µg/m3, and the 8-h maximum O3 concentration could be reduced by 0.34 µg/m3 on the average (up to 1.1 µg/m3 in certain areas). Our research indicates that a shift from traditional road transport to cleaner railway and waterway transport could deliver transportation and environmental benefits to port cities.