bluuebunny/crossref_metadata_2025 huggingface dataset:
Encapsulated vaterite-calcite CaCO3 particles loaded with Mg2+ and Cu2+ ions with sustained release promoting osteogenesis and angiogenesis
Authors: Fan Lu , Körte Fabian , Rudt Alexander , Jung Ole , Burkhardt Claus , Barbeck Mike , Xiong Xin
Published: August 2022

Bioactive cations, including calcium, copper and magnesium, have shown the potential to become the alternative to protein growth factor-based therapeutics for bone healing. Ion substitutions are less costly, more stable, and more effective at low concentrations. Although they have been shown to be effective in providing bone grafts with more biological functions, the precise control of ion release kinetics is still a challenge. Moreover, the synergistic effect of three or more metal ions on bone regeneration has rarely been studied. In this study, vaterite-calcite CaCO3 particles were loaded with copper (Cu2+) and magnesium (Mg2+). The polyelectrolyte multilayer (PEM) was deposited on CaCuMg-CO3 particles via layer-by-layer technique to further improve the stability and biocompatibility of the particles and to enable controlled release of multiple metal ions. The PEM coated microcapsules were successfully combined with collagen at the outmost layer, providing a further stimulating microenvironment for bone regeneration. The in vitro release studies showed remarkably stable release of Cu2+ in 2 months without initial burst release. Mg2+ was released in relatively low concentration in the first 7 days. Cell culture studies showed that CaCuMg-PEM-Col microcapsules stimulated cell proliferation, extracellular maturation and mineralization more effectively than blank control and other microcapsules without collagen adsorption (Ca-PEM, CaCu-PEM, CaMg-PEM, CaCuMg-PEM). In addition, the CaCuMg-PEM-Col microcapsules showed positive effects on osteogenesis and angiogenesis in gene expression studies. The results indicate that such a functional and controllable delivery system of multiple bioactive ions might be a safer, simpler and more efficient alternative of protein growth factor-based therapeutics for bone regeneration. It also provides an effective method for functionalizing bone grafts for bone tissue engineering.
Actin stabilization in cell migration
Authors: Baltes Carsten , Thalla Divyendu Goud , Kazmaier Uli , Lautenschläger Franziska
Published: August 2022

Actin is a cytoskeletal filament involved in numerous biological tasks, such as providing cells a shape or generating and transmitting forces. Particularly important for these tasks is the ability of actin to grow and shrink. To study the role of actin in living cells this dynamic needs to be targeted. In the past, such alterations were performed by destabilizing actin. In contrast, we used the natural compound miuraenamide A in living retinal pigmented epithelial (RPE-1) cells to stabilize actin filaments and show that it decreases actin filament dynamics and elongates filament length. Cells treated with miuraenamide A increased their adhesive area and express more focal adhesion sites. These alterations result in a lower migration speed as well as a shift of nuclear position. We therefore postulate that miuraenamide A is a promising new tool to stabilize actin polymerization and study cellular behavior such as migration.
Functional roles of ADP-ribosylation writers, readers and erasers
Authors: Li Ping , Lei Yushuang , Qi Jia , Liu Wanqin , Yao Kai
Published: August 2022

ADP-ribosylation is a reversible post-translational modification (PTM) tightly regulated by the dynamic interplay between its writers, readers and erasers. As an intricate and versatile PTM, ADP-ribosylation plays critical roles in various physiological and pathological processes. In this review, we discuss the major players involved in the ADP-ribosylation cycle, which may facilitate the investigation of the ADP-ribosylation function and contribute to the understanding and treatment of ADP-ribosylation associated disease.
Peritoneal resident macrophages in tumor metastasis and immunotherapy
Authors: Zhang Yu , Ouyang Dongyun , Chen Youhai H. , Xia Houjun
Published: August 2022

Macrophages residing in various tissues play crucial roles in innate immunity, tissue repair, and immune homeostasis. The development and differentiation of macrophages in non-lymphoid tissues are highly regulated by the tissue microenvironment. Peritoneum provides a unique metastatic niche for certain types of tumor cells. As the dominant immune cell type in peritoneal cavity, macrophages control the immune response to tumor and influence the efficacy of anti-tumor therapy. Considering the heterogeneity of macrophages in origin, metabolism, and function, it is always challenging to define the precise roles of macrophages in tumor microenvironment. We review here recent progresses in peritoneal resident macrophage research in the context of physiological and metastatic tumor conditions, which may benefit the development of new anti-tumor therapies through targeting macrophages.
Targeting of the intracellular redox balance by metal complexes towards anticancer therapy
Authors: Murillo María Isabel , Gaiddon Christian , Le Lagadec Ronan
Published: August 2022

The development of cancers is often linked to the alteration of essential redox processes, and therefore, oxidoreductases involved in such mechanisms can be considered as attractive molecular targets for the development of new therapeutic strategies. On the other hand, for more than two decades, transition metals derivatives have been leading the research on drugs as alternatives to platinum-based treatments. The success of such compounds is particularly due to their attractive redox kinetics properties, favorable oxidation states, as well as routes of action different to interactions with DNA, in which redox interactions are crucial. For instance, the activity of oxidoreductases such as PHD2 (prolyl hydroxylase domain-containing protein) which can regulate angiogenesis in tumors, LDH (lactate dehydrogenase) related to glycolysis, and enzymes, such as catalases, SOD (superoxide dismutase), TRX (thioredoxin) or GSH (glutathione) involved in controlling oxidative stress, can be altered by metal effectors. In this review, we wish to discuss recent results on how transition metal complexes have been rationally designed to impact on redox processes, in search for effective and more specific cancer treatments.
Identification of a non-canonical G3BP-binding sequence in a Mayaro virus nsP3 hypervariable domain
Authors: Neyret Aymeric , Bernard Eric , Aïqui-Reboul-Paviet Olivier , Bakhache William , Eldin Patrick , Chaloin Laurent , Briant Laurence
Published: August 2022

Ras-GTPase-activating SH3 domain-binding-proteins 1 (G3BP1) and 2 (G3BP2) are multifunctional RNA-binding proteins involved in stress granule nucleation, previously identified as essential cofactors of Old World alphaviruses. They are recruited to viral replication complexes formed by the Chikungunya virus (CHIKV), Semliki Forest virus (SFV), and Sindbis virus (SINV) via an interaction with a duplicated FGxF motif conserved in the hypervariable domain (HVD) of virus-encoded nsP3. According to mutagenesis studies, this FGxF duplication is strictly required for G3BP binding and optimal viral growth. Contrasting with this scenario, nsP3 encoded by Mayaro virus (MAYV), an arthritogenic virus grouped with Old World alphaviruses, contains a single canonical FGxF sequence. In light of this unusual feature, we questioned MAYV nsP3/G3BPs relationships. We report that G3BP1 and G3BP2 are both required for MAYV growth in human cells and bind nsP3 protein. In infected cells, they are recruited to nsP3-containing cytosolic foci and active replication complexes. Unexpectedly, deletion of the single FGxF sequence in MAYV nsP3 did not abolish these phenotypes. Using mutagenesis and in silico modeling, we identify an upstream FGAP amino acid sequence as an additional MAYV nsP3/G3BP interaction motif required for optimal viral infectivity. These results, therefore, highlight a non-conventional G3BP binding sequence in MAYV nsP3.
Association of Early and Supernormal Vascular Aging categories with cardiovascular disease in the Chinese population
Authors: Cao Qiuyu , Li Mian , Wang Tiange , Chen Yuhong , Dai Meng , Zhang Di , Xu Yu , Xu Min , Lu Jieli , Wang Weiqing , Ning Guang , Bi Yufang , Zhao Zhiyun
Published: August 2022

Background

Early Vascular Aging and Supernormal Vascular Aging are two extreme phenotypes of vascular aging, and people in the two categories demonstrate distinct clinical characteristics and cardiovascular prognosis. However, the clinical implication of vascular aging categories in the Asian or Chinese population has not been investigated. We aimed to investigate the association between vascular aging categories and cardiovascular events in a Chinese cohort.

Methods

We explored the association of vascular aging categories with incident cardiovascular disease in a community cohort in Shanghai, China, which included 10,375 participants following up for 4.5 years. Vascular age was predicted by a multivariable linear regression model including classical risk factors and brachial-ankle pulse wave velocity. Early and Supernormal vascular aging groups were defined by 10% and 90% percentiles of Δ-age, which was calculated as chronological minus vascular age.

Results

We found that cardiovascular risk significantly increased in Early [hazard ratio (HR), 1.597 (95% CI, 1.043–2.445)] and decreased in Supernormal [HR, 0.729 (95% CI, 0.539–0.986)] vascular aging individuals, comparing with normal vascular aging subjects. The associations were independent of the Framingham risk score. Early vascular aging individuals also showed an elevated risk of total mortality [HR, 2.614 (95% CI, 1.302–5.249)]. Further, the associations of vascular aging categories with cardiovascular risk were much stronger in females than in males. Vascular aging categories with different cutoff levels expressed as percentiles (10th, 20th, and 25th) of Δ-age showed similar associations with cardiovascular risk.

Conclusions

In conclusion, the vascular aging categories could identify people with different levels of cardiovascular risk in the Chinese population, particularly in women.
Microbiota-derived short-chain fatty acids: Implications for cardiovascular and metabolic disease
Authors: Lu Yingdong , Zhang Yang , Zhao Xin , Shang Chang , Xiang Mi , Li Li , Cui Xiangning
Published: August 2022

Cardiovascular diseases (CVDs) have been on the rise around the globe in the past few decades despite the existing guidelines for prevention and treatment. Short-chain fatty acids (SCFAs) are the main metabolites of certain colonic anaerobic bacterial fermentation in the gastrointestinal tract and have been found to be the key metabolites in the host of CVDs. Accumulating evidence suggest that the end-products of SCFAs (including acetate, propionate, and butyrate) interact with CVDs through maintaining intestinal integrity, anti-inflammation, modulating glucolipid metabolism, blood pressure, and activating gut-brain axis. Recent advances suggest a promising way to prevent and treat CVDs by controlling SCFAs. Hence, this review tends to summarize the functional roles carried out by SCFAs that are reported in CVDs studies. This review also highlights several novel therapeutic interventions for SCFAs to prevent and treat CVDs.
Clinical implications of central blood pressure measured by radial tonometry and automated office blood pressure measured using automatic devices in cardiovascular diseases
Authors: Kwon Ami , Kim Gee-Hee , Kim Min-Sik
Published: August 2022

Objective

Central aortic systolic blood pressure (CBP) measured by carotid-femoral pulse wave analysis (cfPWA) is a gold standard method to estimate true arterial pressure. However, the impact of the CBP level measured by radial PWA on cardiovascular (CV) risk assessment is unclear. This study aimed to determine the impact on CV outcome assessment and the association between the optimal levels of non-invasively measured CBP and automated office blood pressure (OBP) in clinical practice.

Materials and methods

A total of 2,115 patients underwent non-invasive semiautomated radial artery applanation tonometry (Omron HEM-9000AI) in the Department of Internal Medicine, St. Vincent’s Hospital, from July 2011 to December 2015. The patients were followed for at least 5 years, and atherosclerotic cardiovascular (ASCVD) outcomes were collected.

Results

Among 2,115 patients (mean age 58 ± 14 years, 50.4% men) who were followed up, the median follow-up period was 52 months (range: 1–104 months). The total number of patients with ASCVD events was 163 (7.70%). In multivariate Cox regression analysis, a CBP of more than 125 mmHg and an automated OBP of more than 131 mmHg were independently associated with a significant increase in ASCVD outcomes. After adjusting for confounding factors, the hazard ratio for ASCVD events increased by 12.5, 11.7, and 12.7%, for every 10 mmHg increase in automated OBP, CBP, and central pulse pressure (PP), respectively.

Conclusion

This study demonstrated that the automated OBP measured using the method used in real clinical practice and CBP measured by radial tonometry were associated with an increased risk for adverse ASCVD outcomes.
Preoperative myocardial fibrosis is associated with worse survival after alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy: A delayed enhanced cardiac magnetic resonance study
Authors: Chen Youzhou , Zhao Xingshan , Yuan Jiansong , Zhang Yan , Liu Wei , Qiao Shubin
Published: August 2022

Background

Prior studies have shown that myocardial fibrosis can be detected by late gadolinium enhancement (LGE) of cardiac magnetic resonance (CMR) and might be associated with higher mortality risk in hypertrophic cardiomyopathy (HCM). The objective of this study was to examine the prognostic utility of CMR in patients with hypertrophic obstructive cardiomyopathy (HOCM) undergoing alcohol septal ablation (ASA).

Materials and methods

We conducted a retrospective study which consisted of 183 consecutive patients with symptomatic drug-refractory HOCM who underwent CMR for assessment of myocardial fibrosis before ASA. The cardiovascular disease related survival was evaluated according to LGE-CMR status.

Results

The cohort comprised 74 (40.4%) women with a mean age of 51 ± 8 years. Preoperative myocardial fibrosis was detected in 148 (80.9%) patients. After a median of 6 years (range 2–11 years) follow-up, adverse clinical events occurred in 14 (7.7%) patients. Multivariate-adjusted Cox regression analyses revealed that age [hazard ratio (HR) 1.142 (1.059–1.230), p = 0.001] and LGE [HR 1.170 (1.074–1.275), p < 0.001] were independent predictors of cardiovascular mortality during follow-up.

Conclusion

Preoperative myocardial fibrosis measured by LGE-CMR was an independent predictor of increased adverse clinical outcomes in patients with HOCM undergoing ASA and could be used for the pre-operative evaluation of risk stratification and long-term prognosis after ASA in these patients.
Polyvinyl alcohol coating prevents platelet adsorption and improves mechanical property of polycaprolactone-based small-caliber vascular graft
Authors: Wakabayashi Naohiro , Yoshida Takumi , Oyama Kyohei , Naruse Daisuke , Tsutsui Masahiro , Kikuchi Yuta , Koga Daisuke , Kamiya Hiroyuki
Published: August 2022

The low patency of synthetic vascular grafts hinders their practical applicability. Polyvinyl alcohol (PVA) is a non-toxic, highly hydrophilic polymer; thus, we created a PVA-coated polycaprolactone (PCL) nanofiber vascular graft (PVA–PCL graft). In this study, we examine whether PVA could improve the hydrophilicity of PCL grafts and evaluate its in vivo performance using a rat aorta implantation model. A PCL graft with an inner diameter of 1 mm is created using electrospinning (control). The PCL nanofibers are coated with PVA, resulting in a PVA–PCL graft. Mechanical property tests demonstrate that the PVA coating significantly increases the stiffness and resilience of the PCL graft. The PVA–PCL surface exhibits a much smaller sessile drop contact angle when compared with that of the control, indicating that the PVA coating has hydrophilic properties. Additionally, the PVA–PCL graft shows significantly less platelet adsorption than the control. The proposed PVA–PCL graft is implanted into the rat’s abdominal aorta, and its in vivo performance is tested at 8 weeks. The patency rate is 83.3% (10/12). The histological analysis demonstrates autologous cell engraftment on and inside the scaffold, as well as CD31/α-smooth muscle positive neointima regeneration on the graft lumen. Thus, the PVA–PCL grafts exhibit biocompatibility in the rat model, which suggests that the PVA coating is a promising approach for functionalizing PCL.
Prolonged dual antiplatelet therapy after drug-eluting stent implantation in patients with diabetes mellitus: A nationwide retrospective cohort study
Authors: Lee Seung-Jun , Choi Dong-Woo , Kim Choongki , Suh Yongsung , Hong Sung-Jin , Ahn Chul-Min , Kim Jung-Sun , Kim Byeong-Keuk , Ko Young-Guk , Choi Donghoon , Park Eun-Cheol , Jang Yangsoo , Nam Chung-Mo , Hong Myeong-Ki
Published: August 2022

Background

Optimal duration of dual antiplatelet therapy (DAPT) in patients with diabetes mellitus (DM) who have undergone drug-eluting stent (DES) implantation is not clearly established. This study sought to impact of DAPT duration on real-world clinical outcome in patients with or without DM.

Methods

Using a nationwide cohort database, we investigate the association between DAPT duration and clinical outcome between 1 and 3 years after percutaneous coronary intervention (PCI). Primary outcome was all-cause death. Secondary outcomes were cardiovascular death, myocardial infarction, and composite bleeding events. After weighting, 90,100 DES-treated patients were included; 29,544 patients with DM and 60,556 without DM; 31,233 patients with standard DAPT (6–12 months) and 58,867 with prolonged DAPT (12–24 months).

Results

The incidence of all-cause death was significantly lower in patients with prolonged DAPT [8.3% vs. 10.5% in those with standard DAPT, hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.72–0.84] in diabetic patients and non-diabetic patients (4.5% vs. 5.0% in those with standard DAPT, HR 0.89, 95% CI 0.83–0.96). The incidence of composite bleeding events was 5.7% vs. 5.4%, respectively, (HR 1.07, 95% CI 0.96–1.18) in diabetic patients and 5.6% vs. 5.0%, respectively, in non-diabetic patients (HR 1.13, 95% CI 1.05–1.21). There was a significant interaction between the presence of DM and DAPT duration for all-cause death (p for interaction, pint = 0.01) that further favored prolonged DAPT in diabetic patients. However, there was no significant interaction between the presence of DM and DAPT duration for composite bleeding events (pint = 0.38).

Conclusions

This study showed that prolonged rather than standard DAPT might be clinically beneficial in diabetic patients with DES implantation.

Trial registration

ClinicalTrial.gov (NCT04715594).
Current recommendations for revascularization of non-infarct-related artery in patients presenting with ST-segment elevation myocardial infarction and multivessel disease
Authors: Towashiraporn Korakoth
Published: August 2022

ST-segment elevation myocardial infarction (STEMI) is a leading cause of morbidity and mortality worldwide. Immediate reperfusion therapy of the infarct-related artery (IRA) is the mainstay of treatment, either via primary percutaneous coronary intervention (PPCI) or thrombolytic therapy when PPCI is not feasible. Several studies have reported the incidence of multivessel disease (MVD) to be about 50% of total STEMI cases. This means that after successful PPCI of the IRA, residual lesion(s) of the non-IRA may persist. Unlike the atherosclerotic plaque of stable coronary artery disease, the residual obstructive lesion of the non-IRA contains a significantly higher prevalence of vulnerable plaques. Since these lesions are a strong predictor of acute coronary syndrome, if left untreated they are a possible cause of future adverse cardiovascular events. Percutaneous coronary intervention (PCI) of the obstructive lesion of the non-IRA to achieve complete revascularization (CR) is therefore preferable. Several major randomized controlled trials (RCTs) and meta-analyses demonstrated the clinical benefits of the CR strategy in the setting of STEMI with MVD, not only for enhancing survival but also for reducing unplanned revascularization. The CR strategy is now supported by recently published clinical practice guidelines. Nevertheless, the benefit of revascularization must be weighed against the risks from additional procedures.
Drought variability and land degradation in the Amazon River basin
Authors: Paredes-Trejo Franklin , Barbosa Humberto , Giovannettone Jason , Kumar T. V. Lakshmi , Kumar Thakur Manoj , de Oliveira Buriti Catarina
Published: August 2022

The Amazon River Basin (ARB) plays an essential role in global climate regulation. Recent studies have revealed signs of increasing drought conditions in different parts of the basin. Although human activities have degraded large areas, little work has been done to assess whether prolonged drought may exacerbate land degradation. Among different methods for monitoring land degradation, the Sustainable Development Goal (SDG) indicator 15.3.1 adopted by the United Nations Convention to Combat Desertification (UNCCD) allows a comprehensive assessment of the impacts of land degradation due to its multi-factor nature and scalability. The aims of this study are twofold: 1) to assess the status of land degradation using the SDG indicator 15.3.1 from 2001 to 2020 in the Amazon basin; and 2) to explore the relationship between the detectability of land degradation using the UNCCD approach and long-term drought severity. The Standardized Precipitation Index (SPI), Standardized Precipitation-Evapotranspiration Index (SPEI), and self-calibrating Palmer Drought Severity Index (scPDSI) were used as drought indices. The results revealed 757,704 km2 (12.67% of the basin) as degraded land, which was reflected by a downward trend in land productivity dynamics followed by the combined downward trend in land productivity, Soil Organic Carbon (SOC) degradation, and land cover degradation. The largest land degradation hotspot was identified along the southwestern boundary of the Amazon River Basin. Furthermore, there was strong evidence that the detection of land degradation through SDG indicator 15.3.1 is sensitive to long-term drought, particularly when applied to rainfed croplands.
Integrity levels of Chinese college students: An analysis of influencing factors
Authors: Li Xiaohong , Zhao Jin , Yan Wenfan
Published: August 2022

This study explores Chinese college students' integrity status and the influencing factors to understand the best practices of Chinese colleges and universities on the issue of integrity cultivation, which is critical for the quality of Chinese higher education. A mixed method combining the quantitative and qualitative data were applied. Respondents from 63 Chinese higher education institutions to the questionnaire were received, which suggested the medium level of Chinese college students' integrity. Compared with the integrity education in western countries, Chinese higher education institutions pay attention to relationship integrity, financial integrity, and employment integrity in everyday life, in addition to academic integrity. The results of csQCA analysis indicated that the university management played an important role in students' integrity and the main influencing factors are policymaking that is appropriate to students' needs, the platform that caters to students' diversified interests, and the supportive environment for integrity. The interactions among the three factors affect and improve Chinese college students' integrity levels.
Role of the major histocompatibility complex class II protein presentation pathway in bone immunity imbalance in postmenopausal osteoporosis
Authors: Wang Xiaoning , Zhang Xin , Han Yidan , Duan Xinwei , Wang Jianchang , Yan Hui , Wang Shanshan , Xu Yunteng , Zhu Zaishi , Wang Lili , Huang Yanfeng , Lin Qing , Tan Xue , Zhuo Junkuan , Zhang Haifeng , Mao Min , Gou Weiying , Yi Zhouping , Li Xihai
Published: August 2022

Bone immunity regulates osteoclast differentiation and bone resorption and is a potential target for the treatment of postmenopausal osteoporosis (PMOP). The molecular network between bone metabolism and the immune system is complex. However, the molecular mechanism underlying the involvement of the major histocompatibility complex class II (MHC-II) molecule protein presentation pathway in PMOP remains to be elucidated. The MHC-II molecule is a core molecule of the protein presentation pathway. It is combined with the processed short peptide and presented to T lymphocytes, thereby activating them to become effector T cells. T-cell-derived inflammatory factors promote bone remodeling in PMOP. Moreover, the MHC-II molecule is highly expressed in osteoclast precursors. MHC-II transactivator (CIITA) is the main regulator of MHC-II gene expression and the switch for protein presentation. CIITA is also a major regulator of osteoclast differentiation and bone homeostasis. Therefore, we hypothesized that the MHC-II promotes osteoclast differentiation, providing a novel pathogenic mechanism and a potential target for the treatment of PMOP.
The pharmacokinetic and pharmacodynamic properties and short-term outcome of a novel once-weekly PEGylated recombinant human growth hormone for children with growth hormone deficiency
Authors: Liang Yan , Zhang Cai , Wei Haiyan , Du Hongwei , Zhang Gaixiu , Yang Yu , Zhang Hua , Gong Haihong , Li Pin , Song Fuying , Xu Zhuangjian , He Ruoyi , Zhou Weidong , Zheng Heng , Sun Li , Luo Xiaoping
Published: August 2022

Objectives

To investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of Y-shape branched PEGylated recombinant human growth hormone (YPEG-rhGH) and evaluate its short-term efficacy and safety in children with growth hormone deficiency (GHD).

Methods

A total of 43 children with GHD from 12 sites in China were enrolled in this randomized, multicenter, active-controlled, double-blind (YPEG-rhGH doses) trial. Patients were randomized 1:1:1:1 to 100, 120, and 140 μg/kg/week of YPEG-rhGH groups and daily rhGH 35 μg/kg/day groups. The treatment lasted 12 weeks. The primary outcome was the area under the curve of the change of insulin-like growth factor-1 (IGF-1). The secondary outcome was the height velocity (HV) increment at week 12.

Results

A dose-dependent response of maximum plasma concentration (Cmax) and area under the concentration-time curves from 0 to 168 hours (AUC0-168h) were observed for YPEG-rhGH. The ratio of Cmax and the ratio of AUC0-168h from the first to the last dosing were 1.09~1.11 and 1.22~1.26 respectively. A YPEG-rhGH dose-dependent increase in area under effect curve (AUEC) of IGF-1 fold change was observed. Model-derived mean IGF-1 SDS was in the normal range for all three YPEG-rhGH doses. At week 12, HV was 7.07, 10.39, 12.27 cm/year, and 11.58 cm/year for YPEG-rhGH 100, 120, and 140 μg/kg/week and daily rhGH respectively. Adherence and safety were consistent with the profile of daily rhGH. No related serious adverse events were reported.

Conclusion

The PK/PD suggests that YPEG-rhGH is suitable for the once-weekly treatment of pediatric GHD. YPEG-rhGH 120 ~ 140 μg/kg/week provides the closest HV increment with similar safety and tolerability compared to daily rhGH 35 μg/kg/day in children with GHD.

Clinical Trial Registration

ClinicalTrials.gov, identifier [NCT04513171].
Epithelial arginase-1 is a key mediator of age-associated delayed healing in vaginal injury
Authors: Wilkinson Holly N. , Reubinoff Benjamin , Shveiky David , Hardman Matthew J. , Menachem-Zidon Ofra Ben
Published: August 2022

Pelvic organ prolapse is a disorder that substantially affects the quality of life of millions of women worldwide. The greatest risk factors for prolapse are increased parity and older age, with the largest group requiring surgical intervention being post-menopausal women over 65. Due to ineffective healing in the elderly, prolapse recurrence rates following surgery remain high. Therefore, there is an urgent need to elucidate the cellular and molecular drivers of poor healing in pelvic floor dysfunction to allow effective management and even prevention. Recent studies have uncovered the importance of Arginase 1 for modulating effective healing in the skin. We thus employed novel in vitro and in vivo vaginal injury models to determine the specific role of Arginase 1 in age-related vaginal repair. Here we show, for the first time, that aged rat vaginal wounds have reduced Arginase 1 expression and delayed healing. Moreover, direct inhibition of Arginase 1 in human vaginal epithelial cells also led to delayed scratch-wound closure. By contrast, activation of Arginase 1 significantly accelerated healing in aged vaginal wounds in vivo, to rates comparable to those in young animals. Collectively, these findings reveal a new and important role for Arginase 1 in mediating effective vaginal repair. Targeting age-related Arginase 1 deficiency is a potential viable therapeutic strategy to promote vaginal healing and reduce recurrence rate after surgical repair of pelvic organ prolapse.
Radioactive iodine in low- to intermediate-risk papillary thyroid cancer
Authors: Zhao Hengqiang , Gong Yiping
Published: August 2022

It remains controversial whether papillary thyroid cancer (PTC) patients with low- to intermediate-risk disease should receive radioactive iodine (RAI) after total thyroidectomy (TT). We aim to identify those who might benefit from RAI treatment in PTC patients with cervical nodal metastasis after TT. Patients were divided into TT and TT+RAI groups from the Surveillance, Epidemiology, and End Results (SEER) database (2004–2018). Overall survival (OS) and cancer-specific survival (CSS) were compared, and propensity score matching (PSM) was performed between groups. A total of 15,179 patients were enrolled, including 3,387 (22.3%) who underwent TT and 11,792 (77.7%) who received TT+RAI. The following characteristics were more likely to present in the TT+RAI group: multifocality, capsular extension, T3, N1b, and more metastatic cervical lymph nodes. RAI was associated with better OS in low- to intermediate-risk PTC patients in the multivariate Cox regression model. The subgroup analysis showed that RAI predicted better OS in patients ≥55 years, American Joint Committee on Cancer (AJCC) stage II, and capsular extension with a hazard ratio (HR) (95% CI) of 0.57 (0.45–0.72), 0.57 (0.45–0.72), and 0.68 (0.51–0.91), respectively. However, RAI failed to improve the prognoses of patients with age <55 years, AJCC stage I, PTC ≤1 cm, and capsular invasion. In the PSM cohort with 3,385 paired patients, TT+RAI treatment predicted better OS compared with TT alone. In addition, TT+RAI predicted better OS in patients with metastatic cervical lymph nodes ≥2, multifocality, extracapsular extension, and American Thyroid Association (ATA) intermediate risk. In conclusion, RAI was associated with better OS in low- to intermediate-risk PTC patients with age ≥55 years, multifocality, extrathyroidal extension, and ATA intermediate risk. However, the survival benefit from RAI may be limited in patients with AJCC stage I, PTC ≤1 cm, unifocality, capsular invasion, and ATA low-risk diseases; these patients even showed pathological cervical lymph node metastasis.
Role of microRNA alternation in the pathogenesis of gouty arthritis
Authors: Luo Zhipan , Yang Fan , Hong Shaocheng , Wang Jianpeng , Chen Bangjie , Li Liangyun , Yang Junfa , Yao Yan , Yang Chenchen , Hu Ying , Wang Shuxian , Xu Tao , Wu Jun
Published: August 2022

Gouty arthritis is a common inflammatory disease. The condition is triggered by a disorder of uric acid metabolism, which causes urate deposition and gout flares. MicroRNAs are a class of conserved small non-coding RNAs that bind to the 3’ untranslated region (UTR) of mRNA and regulate the expression of a variety of proteins at the post-transcriptional level. In recent years, attention has been focused on the role of miRNAs in various inflammatory diseases, including gouty arthritis. It is thought that miRNAs may regulate immune function and inflammatory responses, thereby influencing the onset and progression of the disease. This article mainly reviewed the roles of miRNAs in the pathogenesis of gouty arthritis and prospected their potential as diagnostic and prognostic relevant biomarkers and as possible therapeutic targets.
Food Waste Valorisation for Biogas-Based Bioenergy Production in Circular Bioeconomy: Opportunities, Challenges, and Future Developments
Authors: Singh Puneet Kumar , Mohanty Pratikhya , Mishra Snehasish , Adhya Tapan Kumar
Published: August 2022

The fossil fuel-based linear economy has inherent intricacies such as environmental pollution and the continued need for energy sourcing. Consequently, there has been a shift to a more sustainable circular bio-economy, in which biomass waste is valorised for energy generation while reducing the bulk waste materials and greenhouse gas emissions. In modern bioeconomy, biogas is a primary energy production vehicle. Bio-based economy-enabled technologies result in heat and electricity generation, considerable substitution of fossil fuels for transport, and also the manufacture of additional value-added products and byproducts of economic benefits. Wastes from industrial operations, agriculture, and other anthropogenic activities such as food waste (FW) can be biodigested and transformed into valuable energy sources, nutrient-rich manure, and speciality chemicals. However, for instance, although closed anaerobic membrane bioreactors can totally avoid a microbial runoff, membrane fouling frequently affects the hydraulic performance. Recent developments in anaerobic digestion (AD) of FW have diversified into pretreatment, organic loading, additive supplementation, parametric optimisation, and digestate recirculation to enhance the utility potential of biomass for energy and environment. These numerous anaerobic and microbial interventions support biomass valorisation and related processes, resulting in more efficient biomethanation. Valorisation of FW through biogas-based energy production could serve as an essential cog in the wheel of a circular bioeconomy.
Coordinated Control of a Wind Turbine and Battery Storage System in Providing Fast-Frequency Regulation and Extending the Cycle Life of Battery
Authors: Tang Yuan , Yang Conghuan , Yan Zuanhong , Xue Ying , He Yi
Published: August 2022

Fast-frequency regulation (FFR) is becoming a key measure to enhance the frequency stability of power systems as the penetration of renewables and power electronics continues to grow and the system inertia declines. Although different control methods have been proposed to provide a wind turbine generator (WTG) with a limited capability of virtual inertia and frequency support, the coordination between the WTG and a battery energy storage system (BESS), as well as the potential optimization benefits, have not been fully studied. This study proposes a coordinated control of WTG and BESS that provides FFR to the AC system and at the same time extends the cycle life of the battery. First, a cost effective and SOC-based FFR strategy of BESS alone was proposed. Then, a coordinated FFR method for the WTG–BESS hybrid system under all wind speeds was proposed by analyzing the operational characteristics of WTG. The proposed coordinated strategy improves the FFR performance with a longer cycle life and lower cost of battery under different operating conditions. Simulation results based on varying wind speeds indicate that the proposed FFR strategy raises the frequency nadir and avoids the frequency secondary dip.
Numerical simulation of low reynolds number 2-d rough blade compressor cascade
Authors: Wang Li-Song , Wang Zhong-Yi , Wang Yan-Hua , Wang Meng , Sun Hai-Ou
Published: August 2022

In this paper, a double-circular-arc cascade was used as the research object to study the effect of roughness on the compressor cascade under the conditions of different incoming attack angles. The Reynolds number of the cascade is 1.5×105 . The profile of the suction surface is changed to simulate the change in surface roughness. A uniformly distributed 238 control points were selected on the suction surface profile of the smooth blade. The 238 points are increased randomly along with the normal phase of the wall, and a smooth curve connects these points to obtain a rough suction surface profile. In this study, numerical simulation methods were used to calculate the cascade flow field under 5 kinds of attack angles and 6 kinds of suction surface roughness (including smooth surface). In this paper, k−ω SST and large eddy simulation were used for numerical simulation calculation with the model respectively. The calculation results show that the effect of roughness on the flow field of the cascade is different under different angles of attack. When 70<ks+<130 the rough suction surface can increase the lift coefficient of the compressor blade.
Solving stochastic hydro unit commitment using benders decomposition and modified stochastic dual dynamic programming
Authors: Li Zhuangzhuang , Yang Ping , Yang Yi , Lu Guanpeng , Tang Yufeng
Published: August 2022

This paper proposes a stochastic hydro unit commitment (SHUC) model for a price-taker hydropower producer in a liberalized market. The objective is to maximize the total revenue of the hydropower producer, including the immediate revenue, future revenue (i.e., opportunity cost), and startup and shutdown cost. The market price uncertainty is taken into account through the scenario tree. The solution of the model is a challenging task due to its non-convex and high-dimensional characteristics. A solution method based on the Benders Decomposition (BD) and Modified Stochastic Dual Dynamic Programming (MSDDP) is proposed to solve the problem efficiently. Firstly, the BD is applied to decompose the original problem into a Benders master problem representing the hydro unit commitment and a Benders subproblem representing the optimal operation of the hydropower plants. The Benders subproblem, which contains a large number of integer variables, is further decomposed by the period and solved by the MSDDP proposed in this paper. Finally, we verify the effectiveness of the SHUC model and the performance of the proposed solution method in case studies.
Extracting Unknown Parameters of Proton Exchange Membrane Fuel Cells Using Quantum Encoded Pathfinder Algorithm
Authors: Li Ning , Zhou Guo , Zhou Yongquan , Deng Wu , Luo Qifang
Published: August 2022

Proton exchange membrane fuel cell (PEMFC) is one of the most widely used fuel cell types. Accurate modeling of PEMFC can better facilitate the research of PEMFC and guide designers to design FC products that meet people’s needs. The modeling problem of PEMFC can be transformed into a parametric optimization problem. In order to improve the exploration capability of the pathfinder algorithm, the concept of quantum computing is introduced and a new quantum coded pathfinder optimization algorithm (QPFA) is proposed. QPFA was applied to the extraction of parameters of NedStackPS6, BCS500W and 250W FC, and these models of PEMFC have been applied for commercial use. The experimental results were compared with seven recently proposed metaheuristics and recently published literature, showing the accuracy and high precision of QPFA in extracting PEMFC parameters.
How digital transformation improves corporate environmental management: A review and research agenda
Authors: Xia Jiahui , Wu Zhanchi , Chen Binhai
Published: August 2022

Digital technologies offer opportunities and challenges for corporate environmental management (CEM). In this paper, we provide an overview of the literature on the relationship between digital transformation (DT) and CEM using a systematic review approach in the Antecedents, Decisions, and Outcomes (ADO) format. We review 181 papers published in almost 30 years from 1997 to 2022 and identify studies and areas where DT has impacted on CEM. We find that the literature examining the DT-CEM relationship has surged since 2019 and is concentrated in areas such as green sustainable science technology and environmental sciences. Further, we analyze the economic consequences of DT, the drivers of CEM, and the mechanisms of DT on CEM. Based on the literature analysis, we find that there is still a large gap in the literature studying the mediators and moderators of the DT-CEM relationship. Further, we find that firms with DT have better responsiveness and improved CEM by using digital resources to accurately capture the demands of different stakeholders on the environment. Finally, we provide a research framework and possible research directions, and propose corresponding management insights and policy recommendations.
Spatial-temporal evolution characteristics and drivers of carbon emission intensity of resource-based cities in china
Authors: Song Weixuan , Yin Shanggang , Zhang Yuhan , Qi Lianshanyu , Yi Xing
Published: August 2022

As the key object of carbon emission reduction, resource-based cities’ carbon emission problems are related to the achievement of China’s goals to peak carbon emission and achieve carbon neutrality. In this paper, 115 resource-based cities with abundant natural resources in China were studied, and spatial analysis techniques such as LISA (Local Indicators of Spatial Association) time path and spatial-temporal transition were used to explore their spatial divergence pattern and spatio-temporal evolution characteristics of carbon emission intensity from 2000 to 2019, while geodetector model was used further to reveal their drivers and impacts on the environment. It is found that 1) the carbon emission intensity of resource-based cities shows a significant decreasing trend, with significant differences in carbon emission intensity and its decreasing rate in different development stages and resource-type cities. The overall trend of growing cities, declining cities, mature cities and regenerating cities decreases in order. The carbon emission intensity of cities in the energy, forest industry, general, metal and non-metal categories gradually decrease. The spatial pattern of carbon emission intensity has strong stability, with an overall spatial distribution of high in the north and low in the south. 2) The spatial structure of carbon emission intensity in resource-based cities has strong stability, dependence and integration, with the stability gradually increasing from north to south and the path dependence and locking characteristics of the carbon emission intensity pattern slightly weakened. 3) The spatial divergence of carbon emission intensity in resource-based cities is the result of the action of multiple factors, among which the level of financial investment, urban economic density, urban population density, urban investment intensity and energy use efficiency are the dominant factors. 4) The leading drivers of carbon emission intensity are different in cities at different development stages and with various resources, and grasping the characteristics of carbon emission intensity changes and drivers of various resource-based cities can better provide targeted countermeasures for resource-based cities to achieve carbon emission reduction targets and sustainable development.
An automated work-flow for pinniped surveys: A new tool for monitoring population dynamics
Authors: Infantes Eduardo , Carroll Daire , Silva Willian T. A. F. , Härkönen Tero , Edwards Scott V. , Harding Karin C.
Published: August 2022

Detecting changes in population trends depends on the accuracy of estimated mean population growth rates and thus the quality of input data. However, monitoring wildlife populations poses economic and logistic challenges especially in complex and remote habitats. Declines in wildlife populations can remain undetected for years unless effective monitoring techniques are developed, guiding appropriate management actions. We developed an automated survey workflow using unmanned aerial vehicles (drones) to quantify the number and size of individual animals, using the well-studied Scandinavian harbour seal (Phoca vitulina) as a model species. We compared ground-based counts using telescopes with manual flights, using a zoom photo/video, and pre-programmed flights producing orthomosaic photo maps. We used machine learning to identify and count both pups and older seals and we present a new method for measuring body size automatically. We evaluate the population’s reproductive success using drone data, historical counts and predictions from a Leslie matrix population model. The most accurate and time-efficient results were achieved by performing pre-programmed flights where individual seals are identified by machine learning and their body sizes are measured automatically. The accuracy of the machine learning detector was 95–97% and the classification error was 4.6 ± 2.9 for pups and 3.1 ± 2.1 for older seals during good light conditions. There was a clear distinction between the body sizes of pups and older seals during breeding time. We estimated 320 pups in the breeding season 2021 with the drone, which is well beyond the expected number, based on historical data on pup production. The new high quality data from the drone survey confirms earlier indications of a deteriorating reproductive rate in this important harbour seal colony. We show that aerial drones and machine learning are powerful tools for monitoring wildlife in inaccessible areas which can be used to assess annual recruitment and seasonal variations in body condition.
Using paleoecological data to inform decision making: A deep-time perspective
Authors: Dowsett Harry , Jacobs Peter , de Mutsert Kim
Published: August 2022

Latest climate models project conditions for the end of this century that are generally outside of the human experience. These future conditions affect the resilience and sustainability of ecosystems, alter biogeographic zones, and impact biodiversity. Deep-time records of paleoclimate provide insight into the climate system over millions of years and provide examples of conditions very different from the present day, and in some cases similar to model projections for the future. In addition, the deep-time paleoecologic and sedimentologic archives provide insight into how species and habitats responded to past climate conditions. Thus, paleoclimatology provides essential context for the scientific understanding of climate change needed to inform resource management policy decisions. The Pliocene Epoch (5.3–2.6 Ma) is the most recent deep-time interval with relevance to future global warming. Analysis of marine sediments using a combination of paleoecology, biomarkers, and geochemistry indicates a global mean annual temperature for the Late Pliocene (3.6–2.6 Ma) ∼3°C warmer than the preindustrial. However, the inability of state-of-the-art climate models to capture some key regional features of Pliocene warming implies future projections using these same models may not span the full range of plausible future climate conditions. We use the Late Pliocene as one example of a deep-time interval relevant to management of biodiversity and ecosystems in a changing world. Pliocene reconstructed sea surface temperatures are used to drive a marine ecosystem model for the North Atlantic Ocean. Given that boundary conditions for the Late Pliocene are roughly analogous to present day, driving the marine ecosystem model with Late Pliocene paleoenvironmental conditions allows policymakers to consider a future ocean state and associated fisheries impacts independent of climate models, informed directly by paleoclimate information.