bluuebunny/crossref_metadata_2025 huggingface dataset:
Production and structural characterization of eco-friendly bioemulsifier SC04 from Saccharomyces cerevisiae strain MYN04 with potential applications
Authors: Elsaygh Yasmina A. , Gouda Mona K. , Elbahloul Yasser , Hakim Moustafa Abdel , El Halfawy Nancy M.
Published: September 2023

Background

Bioemulsifiers are natural or microbial-based products with the ability to emulsify hydrophobic compounds in water. These compounds are biodegradable, eco-friendly, and find applications in various industries.

Results

Thirteen yeasts were isolated from different sources in Alexandria, Egypt, and evaluated for their potential to produce intracellular bioemulsifiers. One yeast, isolated from a local market in Egypt, showed the highest emulsification index (EI24) value. Through 26S rRNA sequencing, this yeast was identified as Saccharomyces cerevisiae strain MYN04. The growth kinetics of the isolate were studied, and after 36 h of incubation, the highest yield of cell dry weight (CDW) was obtained at 3.17 g/L, with an EI24 of 55.6%. Experimental designs were used to investigate the effects of culture parameters on maximizing bioemulsifier SC04 production and CDW. The study achieved a maximum EI24 of 79.0 ± 2.0%. Furthermore, the crude bioemulsifier was precipitated with 50% ethanol and purified using Sephadex G-75 gel filtration chromatography. Bioemulsifier SC04 was found to consist of 27.1% carbohydrates and 72.9% proteins. Structural determination of purified bioemulsifier SC04 was carried out using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX), high-performance liquid chromatography (HPLC), and nuclear magnetic resonance spectroscopy (NMR). FTIR spectroscopy revealed characteristic bands associated with carboxyl and hydroxyl groups of carbohydrates, as well as amine groups of proteins. HPLC analysis of monosaccharide composition detected the presence of mannose, galactose, and glucose. Physicochemical characterization of the fraction after gel filtration indicated that bioemulsifier SC04 is a high molecular weight protein-oligosaccharide complex. This bioemulsifier demonstrated stability at different pH values, temperatures, and salinities. At a concentration of 0.5 mg/mL, it exhibited 51.8% scavenging of DPPH radicals. Furthermore, in vitro cytotoxicity evaluation using the MTT assay revealed a noncytotoxic effect of SC04 against normal epithelial kidney cell lines.

Conclusions

This study presents a new eco-friendly bioemulsifier, named SC04, which exhibits significant emulsifying ability, antioxidant and anticancer properties, and stabilizing properties. These findings suggest that SC04 is a promising candidate for applications in the food, pharmaceutical, and industrial sectors.
The association between newborn cord blood steroids and ambient prenatal exposure to air pollution: findings from the ENVIRONAGE birth cohort
Authors: Plusquin Michelle , Wang Congrong , Cosemans Charlotte , Roels Harry A. , Vangeneugden Maartje , Lapauw Bruno , Fiers Tom , T’Sjoen Guy , Nawrot Tim S.
Published: September 2023

Knowledge of whether prenatal exposure to ambient air pollution disrupts steroidogenesis is currently lacking. We investigated the association between prenatal ambient air pollution and highly accurate measurements of cord blood steroid hormones from the androgenic pathway.

This study included 397 newborns born between the years 2010 and 2015 from the ENVIRONAGE cohort in Belgium of whom six cord blood steroid levels were measured: 17α-hydroxypregnenolone, 17α-hydroxyprogesterone, dehydroepiandrosterone, pregnenolone, androstenedione, and testosterone. Maternal ambient exposure to PM2.5 (particles with aerodynamic diameter ≤ 2.5 μm), NO2, and black carbon (BC) were estimated daily during the entire pregnancy using a high-resolution spatiotemporal model. The associations between the cord blood steroids and the air pollutants were tested and estimated by first fitting linear regression models and followed by fitting weekly prenatal exposures to distributed lag models (DLM). These analyses accounted for possible confounders, coexposures, and an interaction effect between sex and the exposure. We examined mixture effects and critical exposure windows of PM2.5, NO2 and BC on cord blood steroids via the Bayesian kernel machine regression distributed lag model (BKMR-DLM).

An interquartile range (IQR) increment of 7.96 µg/m3 in PM2.5 exposure during pregnancy trimester 3 was associated with an increase of 23.01% (99% confidence interval: 3.26–46.54%) in cord blood levels of 17α-hydroxypregnenolone, and an IQR increment of 0.58 µg/m³ in BC exposure during trimester 1 was associated with a decrease of 11.00% (99% CI: -19.86 to -0.012%) in cord blood levels of androstenedione. For these two models, the DLM statistics identified sensitive gestational time windows for cord blood steroids and ambient air pollution exposures, in particular for 17α-hydroxypregnenolone and PM2.5 exposure during trimester 3 (weeks 28–36) and for androsterone and BC exposure during early pregnancy (weeks 2–13) as well as during mid-pregnancy (weeks 18–26). We identified interaction effects between pollutants, which has been suggested especially for NO2.

Our results suggest that prenatal exposure to ambient air pollutants during pregnancy interferes with steroid levels in cord blood. Further studies should investigate potential early-life action mechanisms and possible later-in-life adverse effects of hormonal disturbances due to air pollution exposure.
The evolution and heterogeneity of neutrophils in cancers: origins, subsets, functions, orchestrations and clinical applications
Authors: Liu Siyao , Wu Wenchuan , Du Yueshan , Yin Hanlin , Chen Qiangda , Yu Weisheng , Wang Wenquan , Yu Jun , Liu Liang , Lou Wenhui , Pu Ning
Published: September 2023

Neutrophils, the most prevalent innate immune cells in humans, have garnered significant attention in recent years due to their involvement in cancer progression. This comprehensive review aimed to elucidate the important roles and underlying mechanisms of neutrophils in cancer from the perspective of their whole life cycle, tracking them from development in the bone marrow to circulation and finally to the tumor microenvironment (TME). Based on an understanding of their heterogeneity, we described the relationship between abnormal neutrophils and clinical manifestations in cancer. Specifically, we explored the function, origin, and polarization of neutrophils within the TME. Furthermore, we also undertook an extensive analysis of the intricate relationship between neutrophils and clinical management, including neutrophil-based clinical treatment strategies. In conclusion, we firmly assert that directing future research endeavors towards comprehending the remarkable heterogeneity exhibited by neutrophils is of paramount importance.
Structural and biological characterization of pAC65, a macrocyclic peptide that blocks PD-L1 with equivalent potency to the FDA-approved antibodies
Authors: Rodriguez Ismael , Kocik-Krol Justyna , Skalniak Lukasz , Musielak Bogdan , Wisniewska Aneta , Ciesiołkiewicz Agnieszka , Berlicki Łukasz , Plewka Jacek , Grudnik Przemyslaw , Stec Malgorzata , Siedlar Maciej , Holak Tad A. , Magiera-Mularz Katarzyna
Published: September 2023

Recent advances in immuno-oncology have opened up new and impressive treatment options for cancer. Notwithstanding, overcoming the limitations of the current FDA-approved therapies with monoclonal antibodies (mAbs) that block the PD-1/PD-L1 pathway continues to lead to the testing of multiple approaches and optimizations. Recently, a series of macrocyclic peptides have been developed that exhibit binding strengths to PD-L1 ranging from sub-micromolar to micromolar. In this study, we present the most potent non-antibody-based PD-1/PD-L1 interaction inhibitor reported to date. The structural and biological characterization of this macrocyclic PD-L1 targeting peptide provides the rationale for inhibition of both PD-1/PD-L1 and CD80/PD-L1 complexes. The IC50 and EC50 values obtained in PD-L1 binding assays indicate that the pAC65 peptide has potency equivalent to the current FDA-approved mAbs and may have similar activity to the BMS986189 peptide, which entered the clinical trial and has favorable safety and pharmacokinetic data. The data presented here delineate the generation of similar peptides with improved biological activities and applications not only in the field of cancer immunotherapy but also in other disorders related to the immune system.
Pulmonary toxicity and translocation of gallium phosphide nanowires to secondary organs following pulmonary exposure in mice
Authors: Berthing Trine , Lard Mercy , Danielsen Pernille H. , Abariute Laura , Barfod Kenneth K. , Adolfsson Karl , Knudsen Kristina B. , Wolff Henrik , Prinz Christelle N. , Vogel Ulla
Published: September 2023

Background

III-V semiconductor nanowires are envisioned as being integrated in optoelectronic devices in the near future. However, the perspective of mass production of these nanowires raises concern for human safety due to their asbestos- and carbon nanotube-like properties, including their high aspect ratio shape. Indeed, III-V nanowires have similar dimensions as Mitsui-7 multi-walled carbon nanotubes, which induce lung cancer by inhalation in rats. It is therefore urgent to investigate the toxicological effects following lung exposure to III-V nanowires prior to their use in industrial production, which entails risk of human exposure. Here, female C57BL/6J mice were exposed to 2, 6, and 18 µg (0.12, 0.35 and 1.1 mg/kg bw) of gallium phosphide (III-V) nanowires (99 nm diameter, 3.7 μm length) by intratracheal instillation and the toxicity was investigated 1, 3, 28 days and 3 months after exposure. Mitsui-7 multi-walled carbon nanotubes and carbon black Printex 90 nanoparticles were used as benchmark nanomaterials.

Results

Gallium phosphide nanowires induced genotoxicity in bronchoalveolar lavage cells and acute inflammation with eosinophilia observable both in bronchoalveolar lavage and lung tissue (1 and 3 days post-exposure). The inflammatory response was comparable to the response following exposure to Mitsui-7 multi-walled carbon nanotubes at similar dose levels. The nanowires underwent partial dissolution in the lung resulting in thinner nanowires, with an estimated in vivo half-life of 3 months. Despite the partial dissolution, nanowires were detected in lung, liver, spleen, kidney, uterus and brain 3 months after exposure.

Conclusion

Pulmonary exposure to gallium phosphide nanowires caused similar toxicological effects as the multi-walled carbon nanotube Mitsui-7.

Graphical Abstract
NIR-triggered thermosensitive polymer brush coating modified intraocular lens for smart prevention of posterior capsular opacification
Authors: Qin Chen , Wen Shimin , Fei Fan , Han Yuemei , Wang Haiting , Chen Hao , Lin Quankui
Published: September 2023

Posterior capsule opacification (PCO) is the most common complication after cataract surgery. Drug-eluting intraocular lens (IOLs) is a promising concept of PCO treatment in modern cataract surgery. However, the large dose of drugs in IOL leads to uncontrollable and unpredictable drug release, which inevitably brings risks of overtreatment and ocular toxicity. Herein, a low-power NIR-triggered thermosensitive IOL named IDG@P(NIPAM-co-AA)-IOL is proposed to improve security and prevent PCO by synergetic controlled drug therapy and simultaneous photo-therapy. Thermosensitive polymer brushes Poly(N-isopropylacrylamide-co-Acrylic acid) (P(NIPAM-co-AA)) is prepared on IOL via surface-initiated reversible addition-fragmentation chain transfer (SI-RAFT) polymerization. Then, Doxorubicin (DOX) and Indocyanine green (ICG) co-loaded Gelatin NPs (IDG NPs) are loaded in P(NIPAM-co-AA) by temperature control. The IDG NPs perform in suit photodynamic & photothermal therapy (PTT&PDT), and the produced heat also provides a trigger for controllable drug therapy with a cascade effect. Such functional IOL shows excellent synergistic drug-phototherapy effect and NIR-triggered drug release behavior. And there is no obvious PCO occurrence in IDG@P(NIPAM-co-AA) IOL under NIR irradiation compared with control group. This proposed IDG@P(NIPAM-co-AA)-IOL serves as a promising platform that combines phototherapy and drug-therapy to enhance the therapeutic potential and medication safety for future clinical application of PCO treatment.
Housing-based syringe services programs to improve access to safer injecting equipment for people who inject drugs in Vancouver, Canada: a spatially oriented qualitative study
Authors: Chayama Koharu Loulou , Ng Cara , Fleming Taylor , Small Will , Sue Kimberly L. , McNeil Ryan
Published: September 2023

Background

Housing environments shape injection drug-related risks and harms and thus represent a critical implementation setting for syringe services programs (SSPs). As critical harm reduction measures, SSPs provide safe injecting equipment to people who inject drugs (PWID). Vancouver, Canada, has well-established syringe distribution programs through which PWID have low-threshold access to unlimited syringes and related injecting equipment, including through non-profit operated supportive housing and single-room occupancy hotels. This study examines the role of housing-based SSPs in distributing injecting equipment to PWID in Vancouver.

Methods

Between January and March 2020, semi-structured, in-depth interviews were conducted in Vancouver with 26 PWID. Interviews were audio-recorded, transcribed, and coded. Salient themes were identified using inductive and deductive approaches.

Results

Many participants accessed SSPs in housing facilities and expressed preference for these programs over those offered at other locations and through other health and social services. Three major themes emerged to explain this preference. First, most participants injected in the buildings where they resided, and housing-based SSPs made injecting equipment available when and where it was most needed. Second, many participants preferred to avoid carrying syringes outside of the places where they inject due to fears that syringe possession may lead to criminal charges or confiscation of syringes and/or illicit drugs by police. Third, for some participants, anti-drug user stigma and concerns over unwillingly disclosing their drug use hindered access to SSPs outside of housing settings. Programs operated within housing facilities often offered greater client anonymity along with more supportive and less stigmatizing environments, particularly in the presence of peer staff.

Conclusion

The current study advances understanding of access to injecting equipment in a setting with city-wide syringe distribution programs. Our findings underscore the benefits of housing-based SSPs and encourage the expansion of such services to maximize access to harm reduction supports for PWID.
X-ray cross-complementing family: the bridge linking DNA damage repair and cancer
Authors: Liu Qiang , Peng Qiu , Zhang Bin , Tan Yueqiu
Published: September 2023

Genomic instability is a common hallmark of human tumours. As a carrier of genetic information, DNA is constantly threatened by various damaging factors that, if not repaired in time, can affect the transmission of genetic information and lead to cellular carcinogenesis. In response to these threats, cells have evolved a range of DNA damage response mechanisms, including DNA damage repair, to maintain genomic stability. The X-ray repair cross-complementary gene family (XRCC) comprises an important class of DNA damage repair genes that encode proteins that play important roles in DNA single-strand breakage and DNA base damage repair. The dysfunction of the XRCC gene family is associated with the development of various tumours. In the context of tumours, mutations in XRCC and its aberrant expression, result in abnormal DNA damage repair, thus contributing to the malignant progression of tumour cells. In this review, we summarise the significant roles played by XRCC in diverse tumour types. In addition, we discuss the correlation between the XRCC family members and tumour therapeutic sensitivity.
CUDC-907, a dual PI3K/histone deacetylase inhibitor, increases meta-iodobenzylguanidine uptake (123/131I-mIBG) in vitro and in vivo: a promising candidate for advancing theranostics in neuroendocrine tumors
Authors: Grand-Guillaume Joana , Mansi Rosalba , Gaonkar Raghuvir H. , Zanger Sandra , Fani Melpomeni , Eugster Philippe J. , Beck Popovic Maja , Grouzmann Eric , Abid Karim
Published: September 2023

Background

Neuroblastoma (NB) and pheochromocytoma/paraganglioma (PHEO/PGL) are neuroendocrine tumors. Imaging of these neoplasms is performed by scintigraphy after injection of radiolabeled meta-iodobenzylguanidine (mIBG), a norepinephrine analog taken up by tumoral cells through monoamine transporters. The pharmacological induction of these transporters is a promising approach to improve the imaging and therapy (theranostics) of these tumors.

Methods

Transporters involved in mIBG internalization were identified by using transfected Human Embryonic Kidney (HEK) cells. Histone deacetylase inhibitors (HDACi) and inhibitors of the PI3K/AKT/mTOR pathway were tested in cell lines to study their effect on mIBG internalization. Studies in xenografted mice were performed to assess the effect of the most promising HDACi on 123I-mIBG uptake.

Results

Transfected HEK cells demonstrated that the norepinephrine and dopamine transporter (NET and DAT) avidly internalizes mIBG. Sodium-4-phenylbutyrate (an HDACi), CUDC-907 (a dual HDACi and PI3K inhibitor), BGT226 (a PI3K inhibitor) and VS-5584 and rapamycin (two inhibitors of mTOR) increased mIBG internalization in a neuroblastoma cell line (IGR-NB8) by 2.9-, 2.1-, 2.5-, 1.5- and 1.3-fold, respectively, compared with untreated cells. CUDC-907 also increased mIBG internalization in two other NB cell lines and in one PHEO cell line. We demonstrated that mIBG internalization occurs primarily through the NET. In xenografted mice with IGR-NB8 cells, oral treatment with 5 mg/kg of CUDC-907 increased the tumor uptake of 123I-mIBG by 2.3- and 1.9-fold at 4 and 24 h post-injection, respectively, compared to the untreated group.

Conclusions

Upregulation of the NET by CUDC-907 lead to a better internalization of mIBG in vitro and in vivo.
Disease evolution in systemic juvenile idiopathic arthritis: an international, observational cohort study through JIRcohort
Authors: Wallimann M. , Bouayed K. , Cannizzaro E. , Kaiser D. , Belot A. , Merlin E. , Poignant S. , Wouters C. , Hofer F. , Saurenmann T. , Koryllou A. , Carlomagno R. , Mejbri M. , Hofer M. , Theodoropoulou K.
Published: September 2023

Background

Systemic juvenile idiopathic arthritis (systemic JIA) is a severe disease with both systemic and joint inflammation. This study aims to identify predictors of disease evolution within the systemic JIA population enrolled in the Juvenile Inflammatory Rheumatism cohort (JIRcohort).

Methods

Observational patient cohort study with 201 recruited children from 4 countries (3 European, 1 North Africa) from 2005 until 2019, using retrospectively (2005–2015) and prospectively (2015–2019) routine care collected data.

Results

Sixty-five patients with complete follow-up data for 24 months after first diagnosis were classified as monophasic (n = 23), polyphasic (n = 6) or persistent group (n = 36) corresponding to their evolution (unique flare, recurrent flares, or persistent disease activity respectively). The patients of the persistent group were more likely to have an earlier disease onset, before the age of 6 (OR 2.57, 95%-CI 0.70–9.46), persistence of arthritis at 12-months post-diagnosis (OR 4.45, 95%-CI 0.58–34.20) and higher use of synthetic DMARD (sDMARD, OR 5.28, 95%-CI 1.39–20.01). Other variables like global assessment by physician and by patient and C Reactive Protein levels at 12-months post-diagnosis were assessed but without any predictive value after adjusting for confounding factors.

Conclusions

Our results suggest that the earlier disease onset, the persistence of arthritis throughout the first year of disease evolution and the need of sDMARD might predict a persistent disease course.
GSDMD gene knockout alleviates hyperoxia-induced hippocampal brain injury in neonatal mice
Authors: Challa Naga Venkata Divya , Chen Shaoyi , Yuan Huijun , Duncan Matthew R. , Moreno William Javier , Bramlett Helen , Dietrich W. Dalton , Benny Merline , Schmidt Augusto F. , Young Karen , Wu Shu
Published: September 2023

Background

Neonatal hyperoxia exposure is associated with brain injury and poor neurodevelopment outcomes in preterm infants. Our previous studies in neonatal rodent models have shown that hyperoxia stimulates the brain’s inflammasome pathway, leading to the activation of gasdermin D (GSDMD), a key executor of pyroptotic inflammatory cell death. Moreover, we found pharmacological inhibition of caspase-1, which blocks GSDMD activation, attenuates hyperoxia-induced brain injury in neonatal mice. We hypothesized that GSDMD plays a pathogenic role in hyperoxia-induced neonatal brain injury and that GSDMD gene knockout (KO) will alleviate hyperoxia-induced brain injury.

Methods

Newborn GSDMD knockout mice and their wildtype (WT) littermates were randomized within 24 h after birth to be exposed to room air or hyperoxia (85% O2) from postnatal days 1 to 14. Hippocampal brain inflammatory injury was assessed in brain sections by immunohistology for allograft inflammatory factor 1 (AIF1) and CD68, markers of microglial activation. Cell proliferation was evaluated by Ki-67 staining, and cell death was determined by TUNEL assay. RNA sequencing of the hippocampus was performed to identify the transcriptional effects of hyperoxia and GSDMD-KO, and qRT-PCR was performed to confirm some of the significantly regulated genes.

Results

Hyperoxia-exposed WT mice had increased microglia consistent with activation, which was associated with decreased cell proliferation and increased cell death in the hippocampal area. Conversely, hyperoxia-exposed GSDMD-KO mice exhibited considerable resistance to hyperoxia as O2 exposure did not increase AIF1 + , CD68 + , or TUNEL + cell numbers or decrease cell proliferation. Hyperoxia exposure differentially regulated 258 genes in WT and only 16 in GSDMD-KO mice compared to room air-exposed WT and GSDMD-KO, respectively. Gene set enrichment analysis showed that in the WT brain, hyperoxia differentially regulated genes associated with neuronal and vascular development and differentiation, axonogenesis, glial cell differentiation, hypoxia-induced factor 1 pathway, and neuronal growth factor pathways. These changes were prevented by GSDMD-KO.

Conclusions

GSDMD-KO alleviates hyperoxia-induced inflammatory injury, cell survival and death, and alterations of transcriptional gene expression of pathways involved in neuronal growth, development, and differentiation in the hippocampus of neonatal mice. This suggests that GSDMD plays a pathogenic role in preterm brain injury, and targeting GSDMD may be beneficial in preventing and treating brain injury and poor neurodevelopmental outcomes in preterm infants.
Supraphysiologic doses of 17β-estradiol aggravate depression-like behaviors in ovariectomized mice possibly via regulating microglial responses and brain glycerophospholipid metabolism
Authors: Li Ming , Zhang Jing , Chen Wendi , Liu Shuang , Liu Xin , Ning Yunna , Cao Yongzhi , Zhao Yueran
Published: September 2023

Background

17β-Estradiol (E2) is generally considered neuroprotective in humans. However, the current clinical use of estrogen replacement therapy (ERT) is based on the physiological dose of E2 to treat menopausal syndrome and has limited therapeutic efficacy. The efficacy and potential toxicity of superphysiological doses of ERT for menopausal neurodegeneration are unknown.

Methods

In this study, we investigated the effect of E2 with a supraphysiologic dose (0.5 mg/kg, sE2) on the treatment of menopausal mouse models established by ovariectomy. We performed the open field, Y-maze spontaneous alternation, forced swim tests, and sucrose preference test to investigate behavioral alterations. Subsequently, the status of microglia and neurons was detected by immunohistochemistry, HE staining, and Nissl staining, respectively. Real-time PCR was used to detect neuroinflammatory cytokines in the hippocampus and cerebral cortex. Using mass spectrometry proteomics platform and LC–MS/ MS-based metabolomics platform, proteins and metabolites in brain tissues were extracted and analyzed. BV2 and HT22 cell lines and primary neurons and microglia were used to explore the underlying molecular mechanisms in vitro.

Results

sE2 aggravated depression-like behavior in ovariectomized mice, caused microglia response, and increased proinflammatory cytokines in the cerebral cortex and hippocampus, as well as neuronal damage and glycerophospholipid metabolism imbalance. Subsequently, we demonstrated that sE2 induced the pro-inflammatory phenotype of microglia through ERα/NF-κB signaling pathway and downregulated the expression of cannabinoid receptor 1 in neuronal cells, which were important in the pathogenesis of depression.

Conclusion

These data suggest that sE2 may be nonhelpful or even detrimental to menopause-related depression, at least partly, by regulating microglial responses and glycerophospholipid metabolism.
Antibody production and characterization of the nucleoprotein of sever fever with thrombocytopenia syndrome virus (SFTSV) for effective diagnosis of SFTSV
Authors: Lee Kyungha , Choi Min Ji , Cho Man-Ho , Choi Dong Ok , Bhoo Seong-Hee
Published: September 2023

Background

Severe fever with thrombocytopenia syndrome (SFTS) is an infectious disease caused by the Dabie bandavirus, [or SFTS virus (SFTSV)] that has become increasingly widespread since it was first reported in 2009. The SFTSV comprises three essential single-stranded RNA gene segments, with the S segment encoding the nucleocapsid (N) protein. Since the N protein is the most abundant and stable viral protein, it is a useful diagnostic marker of infection. Various SFTSV N-protein-based detection methods have been developed. However, given the limited research on antibodies of an SFTSV N-protein, here we report the characterization of the antibodies against SFTSV N protein especially their mapping results which is essential for more efficient and optimized detection of SFTSV.

Methods

To generate SFTSV-N-protein-specific monoclonal antibodies, recombinant full-length SFTSV N protein was expressed in E. coli, and the purified N protein was immunized to mice. The binding epitope positions of the antibodies generated were identified through binding-domain mapping. An antibody pair test using a lateral flow immunoassay (LFIA) was performed to identify effective diagnostic combinations of paired antibodies.

Results

Nine monoclonal antibodies specific for the SFTSV N protein were generated. Antibodies #3(B4E2) and #5(B4D9) were specific for sequential epitopes, while the remainder were specific for conformational epitopes. Antibody #4(C2G1) showed the highest affinity for the SFTSV N protein. The binding domain mapping results indicated the binding regions of the antibodies were divided into three groups. The antibody pair test demonstrated that #3(B4E2)/#4(C2G1) and #4(C2G1)/#5(B4D9) were effective antibody pairs for SFTSV diagnosis.

Conclusions

Effective virus detection requires at least two strong antibodies recognizing separate epitope binding sites of the virus antigen. Here, we generated SFTSV-N-protein-specific monoclonal antibodies and subsequently performed epitope mapping and an antibody pair test to enhance the diagnostic efficiency and accuracy of SFTSV. Confirmation of epitope mappings and their combination immune response to the N protein provide valuable information for effective detection of SFTSV as well as can respond actively to detect a variant SFTSV.
Asthma and COVID-19: a controversial relationship
Authors: Dounce-Cuevas Carlos A. , Flores-Flores Angélica , Bazán Mariana S. , Portales-Rivera Victor , Morelos-Ulíbarri Araceli A. , Bazán-Perkins Blanca
Published: September 2023

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection induces a spectrum of clinical manifestations that depend on the immune response of the patient, i.e., from an asymptomatic form to an inflammatory response with multiorgan deterioration. In some cases, severe cases of SARS-CoV-2 are characterized by an excessive, persistent release of inflammatory mediators known as a cytokine storm. This phenomenon arises from an ineffective T helper (Th)-1 response, which is unable to control the infection and leads to a reinforcement of innate immunity, causing tissue damage. The evolution of the disease produced by SARS-CoV2, known as COVID-19, has been of interest in several research fields. Asthma patients have been reported to present highly variable outcomes due to the heterogeneity of the disease. For example, the Th2 response in patients with allergic asthma is capable of decreasing Th1 activation in COVID-19, preventing the onset of a cytokine storm; additionally, IL-33 released by damaged epithelium in the context of COVID-19 potentiates either Th1 or T2-high responses, a process that contributes to poor outcomes. IL-13, a T2-high inflammatory cytokine, decreases the expression of angiotensin converting enzyme-2 (ACE2) receptor, hindering SARS-CoV-2 entry; finally, poor outcomes have been observed in COVID-19 patients with severe neutrophilic asthma. In other contexts, the COVID-19 lockdown has had interesting effects on asthma epidemiology. The incidence of asthma in the most populated states in Mexico, including Tamaulipas, which has the highest asthma incidence in the country, showed similar tendencies independent of how strict the lockdown measures were in each state. As described worldwide for various diseases, a decrease in asthma cases was observed during the COVID-19 lockdown. This decrease was associated with a drop in acute respiratory infection cases. The drop in cases of various diseases, such as diabetes, hypertension or depression, observed in 2020 was restored in 2022, but not for asthma and acute respiratory infections. There were slight increases in asthma cases when in-person classes resumed. In conclusion, although many factors were involved in asthma outcomes during the pandemic, it seems that acute respiratory infection is intimately linked to asthma cases. Social distancing during remote learning, particularly school lockdown, appears to be an important cause of the decrease in cases.
Perceived stress of mental demands at work, objective stress and resilience – an analysis of the LIFE-Adult-study
Authors: Jung Franziska U. , Pabst Alexander , Rodriguez Francisca S. , Luppa Melanie , Engel Christoph , Kirsten Toralf , Witte Veronica , Reyes Nigar , Loeffler Markus , Villringer Arno , Riedel-Heller Steffi G.
Published: September 2023

Background

So far, previous research suggests positive effects of mental demands at the workplace. However, it may depend on how stressfull these demands are perceived on an individual level.

Objective

The aim was to build on previous research by investigating how mental demands are related to stress, overload, and work discontent and whether this relationship is mediated by individuals resources, such as resilience.

Method

A sub-sample of the LIFE Adult Cohort (n = 480) was asked to answer questions on sociodemographic characteristics, objective stress (using the Trier Inventory of Chronic Stress (TICS)), and perceptions of stress with regard to verbal and executive mental demands at work.

Results

According to generalized linear regression models, higher verbal as well as executive mental demands were associated with higher levels of chronic stress, work overload and discontent. Higher levels of resilience were associated with lower levels of these outcomes. Analyses regarding interaction effects revealed that the interaction between resilience and perceived stress of verbal mental demands was significant only in terms of work overload.

Conclusion

Higher perceived stressfulness of mental demands was associated with higher chronic stress, work overload and work discontent. Therefore, mental demands should be targeted by occupational interventions that aim to improve job conditions and employees‘ overall well-being. Besides resilience, other potential influencers or personal resources should be focused on in future studies to develop interventions.
Beyond artificial academic debates: for a diverse, inclusive, and impactful ethnobiology and ethnomedicine
Authors: Reyes-García Victoria
Published: September 2023

In answer to the question “Should ethnobiology and ethnomedicine more decisively foster hypothesis-driven forefront research able to turn findings into policy and abandon more classical folkloric studies?”, in this essay I argue that a major strength of ethnobiology and ethnomedicine is their ability to bridge theories and methods from the natural sciences, the social sciences, and the humanities. Hypothesis-driven research is a powerful way to structure thinking that can lead to forefront research findings. But hypothesis-driven research is not the only way to structure thinking and is not a necessary condition to impact policymaking. To increase policy impact, ethnobiology and ethnomedicine should continue nurturing a mixture of complementary methods and inclusive approaches as fragmentation through opposing different approaches might weaken the discipline. Moreover, with the aim to play a fundamental role in building bridges between different knowledge systems and co-producing solutions towards sustainability, the discipline could benefit from enlarging its epistemological grounds through more collaborative research. Ethnobiologists' research findings, hypothesis-driven, descriptive, or co-constructed can become leverage points to transform knowledge into actionable outcomes in different levels of decision-making.
Ajugol's upregulation of TFEB-mediated autophagy alleviates endoplasmic reticulum stress in chondrocytes and retards osteoarthritis progression in a mouse model
Authors: Wu Jingtao , Yu Heng , Jin Yangcan , Wang Jingquan , Zhou Liwen , Cheng Teng , Zhang Zhao , Lin Binghao , Miao Jiansen , Lin Zhongke
Published: September 2023

Background

Osteoarthritis (OA), a degenerative disease with a high global prevalence, is characterized by the degradation of the extracellular matrix (ECM) and the apoptosis of chondrocytes. Ajugol, a extract derived from the herb Rehmannia glutinosa, has not yet been investigated for its potential in modulating the development of OA.

Methods

We employed techniques such as western blotting, immunofluorescence, immunohistochemistry, X-ray imaging, HE staining, and SO staining to provide biological evidence supporting the role of Ajugol as a potential therapeutic agent for modulating OA. Furthermore, in an in vivo experiment, intra-peritoneal injection of 50 mg/kg Ajugol effectively mitigated the progression of OA following destabilization of the medial meniscus (DMM) surgery.

Results

Our findings revealed that treatment with 50 μM Ajugol activated TFEB-mediated autophagy, alleviating ER stress-induced chondrocyte apoptosis and ECM degradation caused by TBHP. Furthermore, in an in vivo experiment, intra-peritoneal injection of 50 mg/kg Ajugol effectively mitigated the progression of OA following destabilization of the medial meniscus (DMM) surgery.

Conclusion

These results provide compelling biological evidence supporting the role of Ajugol as a potential therapeutic agent for modulating OA by activating autophagy and attenuating ER stress-induced cell death and ECM degradation. The promising in vivo results further suggest the potential of Ajugol as a treatment strategy for OA progression.
COVID-19 vaccination is associated with enhanced efficacy of anti-PD-(L)1 immunotherapy in advanced NSCLC patients: a real-world study
Authors: Qian Yunfei , Zhu Zhuxian , Mo Yin-Yuan , Zhang Ziqiang
Published: September 2023

Background

Coronavirus disease 2019 (COVID-19) vaccine has played a major role in ending the pandemic. However, little is known about the influence of COVID-19 vaccine on the efficacy of immunotherapy in patients with non-small cell lung cancer (NSCLC).

Objectives

The goal of this study is to explore whether COVID-19 vaccine impacts the efficacy of immune checkpoint inhibitors (ICIs) in NSCLC patients.

Methods

We retrospectively analyzed the survival data of ICI-treated 104 patients with stage III–IV NSCLC, who either received COVID-19 vaccination (n = 25) or no vaccination (n = 79). The potential risk factors, in particular roles of COVID-19 vaccination in the efficacy of ICIs in these patients, were evaluated.

Results

Our results showed significantly improved ORR (28.0% vs. 11.39%, p = 0.05) and DCR (88.0% vs. 54.43%, p = 0.005) in the COVID-19 vaccinated group compared with the non-vaccinated group. Regarding the long-term survival benefits, COVID-19 vaccine showed profound influence both on the PFS (HR = 0.16, p = 0.021) and OS (HR = 0.168, p = 0.019) in patients with NSCLC under ICIs treatment. The PFS (p < 0.001) or OS (p < 0.001) was significantly improved in the COVID-19 vaccinated group, compared with the non-vaccinated group. Moreover, CD4 T cell (p = 0.047) level was higher in the COVID-19 vaccinated group than in the non-vaccinated group.

Conclusions

COVID-19 vaccination enhances anti-PD-1 immunotherapy efficacy in patients with stage III–IV NSCLC, suggesting that COVID-19 vaccination may provide additional benefit to NSCLC patients.
Associations over the COVID-19 pandemic period and the mental health and substance use of youth not in employment, education or training in Ontario, Canada: a longitudinal, cohort study
Authors: Quinlan-Davidson Meaghen , Shan Di , Courtney Darren , Barbic Skye , Cleverley Kristin , Hawke Lisa D. , Ma Clement , Prebeg Matthew , Relihan Jacqueline , Szatmari Peter , Henderson J. L.
Published: September 2023

Background

The economic shutdown and school closures associated with the COVID-19 pandemic have negatively influenced many young people’s educational and training opportunities, leading to an increase in youth not in education, employment, or training (NEET) globally and in Canada. NEET youth have a greater vulnerability to mental health and substance use problems, compared to their counterparts who are in school and/or employed. There is limited evidence on the association between COVID-19 and NEET youth. The objectives of this exploratory study included investigating: longitudinal associations between the COVID-19 pandemic and the mental health and substance use (MHSU) of NEET youth; and MHSU among subgroups of NEET and non-NEET youth.

Methods

618 youth (14–28 years old) participated in this longitudinal, cohort study. Youth were recruited from four pre-existing studies at the Centre for Addiction and Mental Health. Data on MHSU were collected across 11 time points during the COVID-19 pandemic (April 2020-August 2022). MHSU were measured using the CoRonavIruS Health Impact Survey Youth Self-Report, the Global Appraisal of Individual Needs Short Screener, and the PTSD Checklist for DSM-5. Linear Mixed Models and Generalized Estimating Equations were used to analyze associations of NEET status and time on mental health and substance use. Exploratory analyses were conducted to investigate interactions between sociodemographic characteristics and NEET status and time.

Results

At baseline, NEET youth were significantly more likely to screen positive for an internalizing disorder compared to non-NEET youth (OR = 1.92; 95%CI=[1.26–2.91] p = 0.002). No significant differences were found between youth with, and without, NEET in MHSU symptoms across the study time frame. Youth who had significantly higher odds of screening positive for an internalizing disorder included younger youth (OR = 1.06, 95%CI=[1.00-1.11]); youth who identify as Trans, non-binary or gender diverse (OR = 8.33, 95%CI=[4.17–16.17]); and those living in urban areas (OR = 1.35, 95%CI=[1.03–1.76]), compared to their counterparts. Youth who identify as White had significantly higher odds of screening positive for substance use problems (OR = 2.38, 95%CI=[1.72–3.23]) compared to racialized youth.

Conclusions

Our findings indicate that sociodemographic factors such as age, gender identity, ethnicity and area of residence impacted youth MHSU symptoms over the course of the study and during the pandemic. Overall, NEET status was not consistently associated with MHSU symptoms over and above these factors. The study contributes to evidence on MHSU symptoms of NEET youth.
Evaluating the psychometric properties of the Chinese Depression Anxiety Stress Scale for Youth (DASS-Y) and DASS-21
Authors: Cao Cui-hong , Liao Xiao-ling , Gamble Jeffrey H. , Li Ling-ling , Jiang Xing-Yong , Li Xu-Dong , Griffiths Mark D. , Chen I-Hua , Lin Chung-Ying
Published: September 2023

Background

In recognizing the need for a reliable and valid instrument to assess psychological distress among children and adolescents, the present study translated the newly developed Depression Anxiety Stress Scale for Youth (DASS-Y) into Chinese, while also comparing its psychometric properties with those of the well-established DASS-21 within a primary and middle school demographic.

Methods

Utilizing a combination of convenience sampling and purposive sampling, a cohort comprising 1,507 primary and 1,131 middle school students was recruited. Rasch analysis, confirmatory factor analysis (CFA), and structural equation modeling (SEM) were used in the data analysis.

Results

Significant differences were observed between the DASS-Y and the DASS-21, notably within the anxiety subscale. The proportions of individuals with clinical mood disorders identified by the two scales demonstrated a significant disparity. Both scales, following an adjustment of responses, exhibited satisfactory internal consistency and convergent validity, with the acceptance of a three-factor structure. Furthermore, the DASS-Y showed superior discriminant validity relative to the DASS-21, providing more compelling evidence regarding concurrent validity.

Conclusion

Overall, the Chinese version of the DASS-Y demonstrated superior robustness to the DASS-21 in terms of psychometric properties. The findings provide initial evidence for the psychometric properties of the DASS-Y from another culture.
Effect of surgical approach on the treatment of Morton's neuroma: a systematic review and meta‐analysis
Authors: Zhang Jiayao , Li Jing , Cai Wufeng , Zheng Kaiwen , Huang Xihao , Rong Xin , Li Qi
Published: September 2023

Background

Surgical resection of Morton's neuroma includes dorsal and plantar approaches. However, there is no consensus on the choice of approach in clinic. The purpose of this study was to conduct a systematic review and meta‐analysis to compare the surgical results of dorsal and plantar approaches.

Methods

The literatures of PubMed, Cochrane library, Embase and Web of Science were searched on April 26th, 2023. A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis guidelines. The data were extracted after screening the literature and evaluating the quality of the methodology included in the study. The RevMan5.4 software was used to analyze and calculate the OR value and 95% confidence interval.

Results

A total of 7 randomized controlled trials and comparative studies were published, of which only 5 were included. There were 158 feet via plantar approach (plantar group, PG) and 189 via dorsal approach (dorsal group, DG). There was no significant difference between PG and DG in overall adverse events, sensory problems, incision infection and deep vein thrombosis (p > 0.05). In terms of scar problems, PG showed more than DG (OR, 2.90[95%CI, 1.40 to 5.98]; p = 0.004). Other outcome indicators such as visual analogue scale (VAS) scores and American Orthopedic Foot and Ankle Society (AOFAS) scores were difficult to be included in the comparison.

Conclusions

Based on the relatively low quality and small amount of available evidence, the meta‐analysis conducted produces a hypothesis that the frequency of adverse events in surgical treatment of Morton's neuroma, dorsal approach and plantar approach may be the same, but the types are different. More high‐level evidence is needed to further verify this hypothesis.
Out-of-hospital cardiac arrest in children: an epidemiological study based on the German Resuscitation Registry identifying modifiable factors for return of spontaneous circulation
Authors: Katzenschlager Stephan , Kelpanides Inga K. , Ristau Patrick , Huck Matthias , Seewald Stephan , Brenner Sebastian , Hoffmann Florian , Wnent Jan , Kramer-Johansen Jo , Tjelmeland Ingvild B. M. , Weigand Markus A. , Gräsner Jan-Thorsten , Popp Erik
Published: September 2023

Aim

This work provides an epidemiological overview of out-of-hospital cardiac arrest (OHCA) in children in Germany between 2007 and 2021. We wanted to identify modifiable factors associated with survival.

Methods

Data from the German Resuscitation Registry (GRR) were used, and we included patients registered between 1st January 2007 and 31st December 2021. We included children aged between > 7 days and 17 years, where cardiopulmonary resuscitation (CPR) was started, and treatment was continued by emergency medical services (EMS). Incidences and descriptive analyses are presented for the overall cohort and each age group. Multivariate binary logistic regression was performed on the whole cohort to determine the influence of (1) CPR with/without ventilation started by bystander, (2) OHCA witnessed status and (3) night-time on the outcome hospital admission with return of spontaneous circulation (ROSC).

Results

OHCA in children aged < 1 year had the highest incidence of the same age group, with 23.42 per 100 000. Overall, hypoxia was the leading presumed cause of OHCA, whereas trauma and drowning accounted for a high proportion in children aged > 1 year. Bystander-witnessed OHCA and bystander CPR rate were highest in children aged 1–4 years, with 43.9% and 62.3%, respectively. In reference to EMS-started CPR, bystander CPR with ventilation were associated with an increased odds ratio for ROSC at hospital admission after adjusting for age, sex, year of OHCA and location of OHCA.

Conclusion

This study provides an epidemiological overview of OHCA in children in Germany and identifies bystander CPR with ventilation as one primary factor for survival.

Trial registrations German Clinical Trial Register: DRKS00030989, December 28th 2022.

Graphical Abstract
Engineering a marine microalga Chlorella sp. as the cell factory
Authors: Gu Xinping , Deng Ying , Wang Aoqi , Gan Qinhua , Xin Yi , Paithoonrangsarid Kalyanee , Lu Yandu
Published: September 2023

The use of marine microalgae in industrial systems is attractive for converting CO2 into value-added products using saline water and sunlight. The plant nature and demonstrated industrial potential facilitate Chlorella spp. as excellent model organisms for both basic research and commercial application. However, the transformation method has not been developed in marine Chlorella spp., thus genetic engineering is hindered in exploiting the industrial potentialities of these strains. In this study, we provided a transformation protocol for the marine Chlorella strain MEM25, which showed robust characteristics, including high production of proteins and polyunsaturated fatty acids in multiple cultivation systems over various spatial–temporal scales. We showed that transformants could be obtained in a dramatically time-saving manner (comparable to Saccharomyces cerevisiae) with four functional proteins expressed properly. The transgenes are integrated into the genome and can be successfully inherited for more than two years. The development of a marine Chlorella transformation method, in combination with the complete genome, will greatly facilitate more comprehensive mechanism studies and provide possibilities to use this species as chassis for synthetic biology to produce value-added compounds with mutual advantage in neutralization of CO2 in commercial scales.