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Regulation of cell growth and cell division plays fundamental roles in tissue morphogenesis. However, the mechanisms of regulating tissue elongation through cell growth and cell division are still not well understood. The wing imaginal disc of Drosophila provides a model system that has been widely used to study tissue morphogenesis. Here we use a recently developed two-dimensional cellular model to study the mechanisms of regulating tissue elongation in Drosophila wing. We simulate the effects of directional cues on tissue elongation. We also computationally analyze the role of reduced cell size. Our simulation results indicate that oriented cell divisions, oriented mechanical forces, and reduced cell size can all mediate tissue elongation, but they function differently. We show that oriented cell divisions and oriented mechanical forces act as directional cues during tissue elongation. Between these two directional cues, oriented mechanical forces have a stronger influence than oriented cell divisions. In addition, we raise the novel hypothesis that reduced cell size may significantly promote tissue elongation. We find that reduced cell size alone cannot drive tissue elongation. However, when combined with directional cues, such as oriented cell divisions or oriented mechanical forces, reduced cell size can significantly enhance tissue elongation in Drosophila wing. Furthermore, our simulation results suggest that reduced cell size has a short-term effect on cell topology by decreasing the frequency of hexagonal cells, which is consistent with experimental observations. Our simulation results suggest that cell divisions without cell growth play essential roles in tissue elongation. [ABSTRACT FROM AUTHOR]

By presenting the phase properties of bistability in amplitude-modulation atomic force microscopy, we put forward a technique, the constant-phase mode, which may eliminate bistability. Using this approach, we keep the phase shift between driving and oscillation constant, slightly above −90°. In addition to the adjustment of the free amplitude, we add to amplitude-modulation atomic force microscopy another feedback so that the tip always oscillates in the high-amplitude state. A numerical simulation is carried out to demonstrate that the algorithm prevents bistability effectively. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel parallel mechanism improves bandwidth of the flexure-based stage. • A decoupler based on circular hinges reduces the coupling between XY axes. • The stage realizes millimeter workspace and high bandwidth simultaneously. This paper presents the design of a flexure-based parallel XY micropositioning stage with millimeter workspace and high bandwidth. The large range micropositioning requires the workspace of flexure-based stage to reach millimeter level. Meanwhile, the structural bandwidth of the flexure-based stage with large range is relatively low, which limits the scan rate and is required to be improved. A novel parallel mechanism is implemented to improve the structural bandwidth of the millimeter level flexure-based XY stage by removing redundant mass. The coupling between the working axes is reduced by a decoupler based on circular hinges. The mechanical performances of the designed XY stage are analyzed by theoretical models and verified by finite element analysis (FEA). Experimental results indicate that the designed XY micropositioning stage is capable of achieving millimeter workspace as well as a relatively high resonance frequency compared with other millimeter level flexure-based XY stages. [ABSTRACT FROM AUTHOR]

Central inhibition, discovered by Sechenov in 1862, suggests that electrically stimulating the forebrain or medulla oblongata in frog generally suppresses reflexes. However, the underlying molecular mechanisms are still unclear. Using ethanol (EtOH), noradrenalin (NA), and other neurotransmitters in thalamic preparations, Sechenov inhibition was stimulated in Bufo toads in this study. The result showed that, similar to Sechenov inhibition, the acute application of EtOH or NA excited the thalamus and prolonged the latency of withdrawal reflex. Our study evidences the involvement of a-adrenoceptors in such central inhibition, and explains the role of acute EtOH application in the induction of reflex inhibition. [ABSTRACT FROM AUTHOR]

The transport sector has produced numerous carbon emissions in China, and it is important to promote low carbon commuting. As an emerging mode of urban low-carbon transportation in China, shared bicycles have been used by more and more citizens on a daily basis, with advantages of green and low-carbon emissions to environment, flexibility for short trips, and convenience for covering the distance between the normal low-carbon transportation and destinations. However, the imbalanced distribution of shared bicycles along subway lines, especially during the morning peak hours, has directly restricted their performance in urban traffic. In this paper, an integer linear program model (ILPM) is proposed to obtain an optimal low-carbon distribution plan of shared bicycles connecting with the subway line (SBCSL) during the morning peak hours. First, an objective function is built to improve the carbon emission reduction of SBCSL. Second, constraint functions are extracted considering the quantity of bicycles to be distributed to the subway line as well as the distribution limits of each subway station. At last, a case study is conducted on the distribution of shared bicycles in Beijing Subway Line 13 of China during the morning peak hours. The results show that the ILPM is of significance to provide optimal distribution scheme of shared bicycles in subway line with different station types including office-oriented, residential-oriented, and hybrid-oriented stations. [ABSTRACT FROM AUTHOR]

Chinese wind power policies have productively promoted the development of wind power and also promoted the process of wind power participation in electricity market transactions. However, with policy emphasis on investment and neglect of utilization, there have been some difficulties in the development of Chinese wind power. To highlight the guiding role of policy and improve the wind power policy system, an analysis of Chinese wind power policies is conducted in this paper. First, aiming at the main components of wind power chain, including wind power construction, grid connection, transmission, and sales, a comprehensive and systematic frame of Chinese wind power policy system is proposed from the three aspects of development planning, administrative management and market transactions. Second, the indicator system of Chinese wind power development effectiveness is extracted, including installed capacity, power generation, power utilization hours, carbon emission reduction, investment, on-grid power price, wind curtailment rate, etc., and the effectiveness of policy implementation is verified. Third, new policy recommendations are proposed from parts of transmission, consumption, and market, for the development of Chinese wind power industry in the 14th Five-Year Plan period and the goal to reach the crest value of carbon dioxide emissions by 2030 and achieve carbon neutrality by 2060. In this paper, advice to supplement and improve the Chinese wind power policy system is provided, which may it promote better development of Chinese wind power in the following decade from the policy point of view. [ABSTRACT FROM AUTHOR]

Adiponectin (AdipoQ) as an adipocytokine has the potential to regulate feeding behavior, but the information about adipoq in fish is limited. In this study, Siberian sturgeon adiponectin (Ssadipoq) gene was cloned encoding 264 amino acids. The amino acid identity of SsAdipoQ was low compared with that of mammals, birds, amphibians and teleost fishes. The expression of Ssadipoq in the hypothalamus was significantly decreased at 1 h and 3 h post feeding, and increased after 15-day fasting. The mature domain of AdipoQ (fAd) was inserted into expression vector pET32a and successfully expressed in Escherichia coli BL21 (DE3) after stimulated by isopropyl-β-d-thiogalactoside. Food intake at 1 h and 3 h post treatment with SsfAd protein decreased significantly (P < 0.05). The mRNA expression of pyy and cck in the valvula intestine was promoted and hypothalamic npy , agrp and pomc mRNA expression were inhibited after treatment with SsfAd protein. Furthermore, hypothalamic ampk subunits expression was associated with peripheral SsfAd treatment. In summary, present study indicate that SsfAd plays an important role in the regulation of food intake and appetite signals in Siberian sturgeon, which provides a basis for further study application of prokaryotic AdipoQ in feeding behavior regulation. • In the hypothalamus, adiponectin expression responded quickly to short-term and long-term changes of feeding status. • Intraperitoneal administration of SsfAd inhibited food intake at 1 h and 3 h post injection in Siberian sturgeon. • Peripheral SsfAd administration affected appetite factors mRNA expression in the hypothalamus and valvula intestine. • Hypothalamic ampkα2 was significantly up-regulated when treated with peripheral SsfAd protein. [ABSTRACT FROM AUTHOR]

Piezoelectric stack actuators with mechanical structure are widely used in scanning probe microscope to achieve high-precision positioning. However, their positioning ranges can only reach a few hundred microns, which cannot meet the demand of large-range imaging, especially for biological samples. To overcome these shortcomings, a flexure-based decoupled XY high-precision and large-range positioning platform with simple and compact mechanical structure is proposed in this paper. Leaf-type flexure hinges are used to achieve large-range positioning. Based on the leaf-type flexure hinges, a novel mechanism called mixed-kinematic mechanism, which combines serial and parallel kinematic mechanism together, is proposed to simplify the mechanical structure of the platform to make it compact. In addition, XY decoupling is achieved by adopting a novel decoupling structure. Structural parameters and the arrangement of hinges are precisely designed to guarantee the millimeter-level positioning range within safe levels. The performances of the platform including positioning range, resonant frequency and safety are analyzed through finite-element analysis. Experimental results of the platform tests demonstrate that the platform can achieve millimeter-level positioning with good decoupling between the two axes. The eigenfrequencies obtained by experiments also indicate that the designed platform is capable of high-speed positioning with large range. [ABSTRACT FROM AUTHOR]

Background and purpose: The relationship between heart rate and the prognosis of patients with large vessel occlusion strokes treated with mechanical thrombectomy (MT) is not well established. This study aimed to evaluate the association of mean heart rate and heart rate variability (HRV) with the clinical outcomes after MT therapy. Methods: Acute ischemic stroke patients undergoing MT therapy were prospectively recruited from March 2020 to November 2022. Their heart rate was collected every hour for the initial 72 h after MT procedure, and the variability of heart rate was measured by standard deviation (SD) and coefficient of variation (CV). All-cause mortality and worsening of functional outcome (change in modified Rankin Scale (mRS) score) at 3-month were captured. Binary logistic regression was used to evaluate the association between heart rate indicators and all-cause mortality. Ordinal logistic regression was used to evaluate the association between heart rate indicators and worsening of functional outcome. Results: Among 191 MT-treated patients, 51(26.7%) patients died at 3-month after stroke. Increased mean heart rate per 10-bpm, heart rate SD and CV per 5-unit were all associated with the increased risk of mortality (adjusted hazard ratio [aHR] with 95% CI: 1.29 [1.09–1.51], 1.19 [1.07–1.32], 1.14 [1.03–1.27]; respectively). Patients in the highest tertile of heart rate SD had an increased risk of mortality (4.62, 1.70-12.52). After using mRS as a continuous variable, we found increased mean heart rate per 10-bpm, heart rate SD and CV per 5-unit were associated with the worsening of functional outcome (adjusted odds ratio [aOR] with 95% CI: 1.35 [1.11–1.64], 1.27 [1.05–1.53], 1.19 [1.02–1.40]; respectively). A linear relationship was observed between mean heart rate or heart rate SD and mortality; while all of the heart rate measures in this study showed a linear relationship with the worsening of functional outcome. Conclusions: Higher mean heart rate and HRV were associated with the increased risk of 3-month all-cause mortality and worse functional outcome after MT therapy for AIS patients. [ABSTRACT FROM AUTHOR]

Although Brain-derived neurotrophic factor (BDNF) has been identified as an orexigenic peptide in zebrafish, its role in regulating feeding behavior in other fish species is still unclear. This study aimed to investigate the regulatory role of BDNF in feeding behavior of Siberian sturgeon (Acipenser baerii). The bdnf and its receptor TrkB genes (Abbdnf and AbTrkB) of Siberian sturgeon were cloned and found to be most highly expressed in the hypothalamus. Short- and long-term fasting experiments showed that Abbdnf and AbTrkB mRNA levels decreased in the hypothalamus after fasting, but increased after refeeding, consistent with the pattern observed for anorexigenic peptides. The NGF(nerve growth factor) structural domain has an important role in mediating the binding of BDNF to the TrkB receptor. To explore the feeding regulatory role of BDNF, recombinant AbBDNFNGF protein was expressed using prokaryotic expression system. Intraperitoneal injection of AbBDNFNGF suppressed cumulative food intake at 1 h, 3 h, and 6 h after administration, and resulted in upregulation of anorexigenic peptides (pomc and leptin) mRNA and downregulation of orexigenic peptides (npy and agrp) mRNA in both central and peripheral tissues. Additionally, AbBDNFNGF injection led to activation of TrkB receptors and pi3k-akt-mtor signaling pathway in the hypothalamus. Overall, this study confirms the anorexigenic effect of BDNF in Siberian sturgeon. [Display omitted] • mRNA for Abbdnf and its receptor AbTrkB is highly expressed in the hypothalamus of Siberian sturgeon and responds to changes in feeding status. • AbBDNFNGF administered via intraperitoneal injection effectively suppressed cumulative food intake at 1, 3, and 6 h post-administration. • Intraperitoneal injection of AbBDNFNGF induced changes in mRNA levels for appetite-regulating peptides in both central and peripheral tissues, activating AbTrkB receptors and the PI3K-Akt-mTOR signaling pathway in the hypothalamus. [ABSTRACT FROM AUTHOR]

• Emission characteristics, OFP, and health risk of fugitive VOCs were characterized. • Chemical material industry was the major contributor to VOCs of fugitive emission. • Fugitive VOCs contributed significantly to the total OFP. • Non-cancer risks and cancer risks of fugitive VOCs were all above the safe level. Fugitive emission from industrial sources may result in ozone formation and health risk, while the exact contribution of this source remains incompletely understood. In this study, emission characteristics, ozone formation potential (OFP) and health risk of fugitive VOCs in 7 representative industries were investigated. Chemical material industry was the dominant contributor to VOCs of fugitive emission in comparison with other industries. The OFP of VOCs from fugitive emission was in the range of 1.45 × 103-3.98 × 105 µg/m3, with a higher value than that of organized emission in seven industries except for the coking industry and the chemical material industry, suggesting that fugitive VOCs should be taken into account while developing control strategies. Acetaldehyde, m,p -xylene, n-nonane, ethylene, vinyl chloridethe and other high OFP-contributing species were the major reactive species that should be targeted. Health risk assessment investigated non-cancer and cancer risks of fugitive VOCs in 7 industries were all above safe level (HR > 1 and LCR > 1 × 10−4), posing remarkable health threats to human health. OVOCs were the main contributor to non-cancer risk, while halohydrocarbons and aromatics contributed most to cancer risks, posing remarkable health threat on human health. Our findings highlighted the contribution of fugitive VOCs on ozone formation and health risk was underestimated, indicating which should be considered in emission control strategies of industrial sources. [Display omitted] [ABSTRACT FROM AUTHOR]

The comprehensive promotion of electric vehicles is critical for green and low-carbon energy transformation and dual-carbon goals in China. Battery swapping station is a hub to meet the battery-swapping demands of EVs and consumes renewable energy power (REP). Moreover, the potential of battery swapping station cluster (BSSC) must be explored urgently. Therefore, the day-ahead dispatching model of BSSC is proposed for the efficient consumption of REP and battery-swapping demands of electric taxis (ETs) in this paper. Firstly, the battery-swapping demands of ETs in dynamic spatiotemporal distribution are aggregated by the KNN algorithm. Secondly, a dual-objective model of the day-ahead dispatching model with economy and efficient consumption of REP is constructed, and the NSGA-II algorithm obtains the optimal strategy. Finally, taking a city of China as an example, the charging-discharging strategy of BSSC is provided. The results show that the day-ahead dispatching model is of practical significance to get an optimal charging-discharging strategy of cluster loads for REP consumption and economic battery-swapping service. • Aggregate the battery-swapping demands of ETs by the KNN algorithm. • Construct a day-ahead scheduling model for balancing CDC of BSSC and REP consumption. • Apply the NSGA-II algorithm to solve the bi-objective model. • Select a city of China for the study to verify the effectiveness of the model. [ABSTRACT FROM AUTHOR]

Backgroud: There were limitations existing in programmed cell‐death ligand 1 (PD‐L1) as predictive biomarkers for breast cancer (BC), hence exploring the correlation between PD‐L1 levels and other biomarkers in BC may become a very useful therapeutic clinical tool. Methods: A total of 301 Chinese patients with different BC subtypes including 47 HR+/HER2+, 185 HR+/HER2−, 38 HR−/HER2+, and 31 triple‐negative breast cancer (TNBC) were enrolled in our study. Next‐generation sequencing based Yuansu450 gene panel was used for genomic alteration identification and PD‐L1 expression was tested using immunohistochemistry. Results: The most prevalent BC‐related mutations were TP53 mutations, followed by mutations in PIK3CA, ERBB2, CDK12, and GATA3 in our Chinese cohort. We found that mutations DDR2 and MYCL were only mutated in HR−/HER2+ subtype, whereas H3‐3A and NRAS mutations were only occurred in HR−/HER2− subtype. The percentage of patients with PD‐L1‐positive expression was higher in patients with HR‐/HER2− mainly due to the percentage of PD‐L1‐high level. Mutational frequencies of TP53, MYC, FAT4, PBRM1, PREX2 were observed to have significant differences among patients with different BC subtypes based on PD‐L1 levels. Moreover, a positive correlation was observed between TMB and PD‐L1 level in HR+/HER2− subtype, and showed that the proportion of patients with high PD‐L1 expression was higher than that of patients with low PD‐L1 expression in the HR+/HER2− and HR+/HER2+ cohorts with high Ki67 expression. Conclusions: The genomic alterations based on PD‐L1 and other biomarkers of different cohorts may provide more possibilities for the treatment of BC with different subtypes. [ABSTRACT FROM AUTHOR]

N−N Atropisomers are a common motif in natural products and represent a significant dimension for exploration in modern pharmaceutical and medicinal chemistry. However, the catalytic atroposelective synthesis of such molecules remains challenging, hampering meaningful development. In particular, an enantioselective synthesis of N−N bisindole atropisomers is unprecedented. Herein, the first enantioselective synthesis of N−N bisindole atropisomers via the palladium‐catalyzed de novo construction of one indole skeleton is presented. A wide variety of N−N axially chiral bisindoles were generated in good yields with excellent enantioselectivities via a cascade condensation/N‐arylation reaction. Structurally diverse indole‐pyrrole, indole‐carbazole, and non‐biaryl‐indole atropisomers possessing a chiral N−N axis were accessed using this protocol. Moreover, investigations using density functional theory (DFT) calculations provided insight into the reaction mechanism and enantiocontrol. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the safety and efficacy of transanal endorectal pull-through (TEPT) and the long-term outcomes in newborns with Hirschsprung disease (HD).Methods: A total of 229 newborns with HD underwent one-stage TEPT between 2007 and 2020, and the diagnoses were confirmed by rectal biopsy. The perioperative clinical course for all patients was reviewed, and the postoperative short- and long-term outcomes were assessed.Results: A total of 229 neonates (187 male and 42 female) had a median age at TEPT of 17 days (range 6-28 days). Sixty-eight patients (29.7%) underwent TEPT combined with an abdominal approach or laparoscopy. Early postoperative complications (using the Clavien-Dindo grading system) were documented in 36 patients (15.7%), and late postoperative complications were noted in 9 patients (3.9%). The follow-up period in the remaining 165 children ranged from 1.2 to 14.0 years (median 5.0 years). A total of 106 of the patients older than four years old took part in an interview about bowel function, and 85 patients (80.2%) had bowel function scores (BFS) ≥ 18.Conclusion: TEPT is effective and safe for HD in the neonatal period and presents with a low rate of complications and an acceptable outcome. [ABSTRACT FROM AUTHOR]

Intermolecular C−H silylation for the synthesis of acyclic silanes bearing a silicon‐stereogenic center in one enantiomeric form remains unknown to date. Herein, we report the first enantioselective intermolecular C−H silylation of heteroarenes for the synthesis of acyclic silicon‐stereogenic heteroarylsilanes. This process undergoes a rhodium‐catalyzed direct intermolecular dehydrogenative Si−H/C−H cross‐coupling, giving access to a variety of acyclic heteroarylated silicon‐stereogenic monohydrosilanes, including bis‐Si‐stereogenic silanes, in decent yields with excellent chemo‐, regio‐, and stereo‐control, which significantly enlarge the chemical space of the optically active silicon‐stereogenic monohydrosilanes. [ABSTRACT FROM AUTHOR]

Purpose: This study was aiming to explore the risk factors contributing to enterostomy in neonates with Hirschsprung disease (HD) to provide a reference for clinicians to make treatment decisions. Methods: Medical records of 284 patients diagnosed with HD during the neonatal period were retrospectively analyzed. The patients were divided into 2 groups based on operative intervention (one stage transanal pull-through, versus enterotomy and staged transanal pull-through). Univariate and multivariable logistic regression analysis was performed to identify risk factors contributing to enterostomy. Results: The incidence of enterostomy was 12.0% (34/284) in neonates with HD. Univariate and multivariate logistic regression analysis showed that serum albumin < 25.4 g/L, radiographic results as subphrenic free air, and level of aganglionosis with long-segment or total colonic aganglionosis (TCA) were independent risk factors of enterostomy in neonates, with OR of 42.045 (6.131, 288.319), 285.558 (26.651, 3059.694) and 15.573 (4.319, 56.157), respectively. Conclusions: The low serum albumin level, bowel perforation, and level of aganglionosis with long-segment or TCA could influence the occurrence of enterostomy in neonates with HD. [ABSTRACT FROM AUTHOR]

[Display omitted] • A NIR fluorescent probe (AOC) is reported for activatable imaging of G4s in living cells and tumors. • AOC displayed a large stokes shift, high sensitivity and satisfactory selectivity for G4s. • AOC not only have the fluorescence imaging capabilities of G4s, but may also have tumor diagnostic capabilities. G4s play a very important role not only in human biological systems but are associated with tumor formation, which is considered as a novel target for the exploitation of anti-tumor drugs. Therefore, it is essential to develop near-infrared (NIR) fluorescent probes to study G4s. In this article, we designed a large stokes shift probe (AOC) which can be activated NIR fluorescent by G4s in living cells and tumor tissue. In vitro experiments shown that AOC exhibited no fluorescence emission in aqueous solution, while significantly enhanced at 768 nm in the presence of the G4s. The optimal excitation wavelength of the probe is about 640 nm, indicating that the probe AOC has a large stokes shift (128 nm). Meanwhile, AOC is dynamically responsive to the concentrations of DNA G4s (22AG, Mito-160) and exhibits high selectivity toward DNA G4s with desirable stability in the physiological pH conditions. Imaging studies of different cell lines have shown that cancer cell lines fluoresced brightly than normal cell lines, implication that the expression of G4s may be higher in tumor cell lines. We further performed fluorescence imaging of tumor tissues using AOC, which showed that tumor tissues had the brightest fluorescence intensity relative to normal organ tissues. These experimental results further suggest that the NIR fluorescent probe may have tumor diagnostic properties with great potential for application. [ABSTRACT FROM AUTHOR]

Dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP), two common types of phthalates, are known to cause reproductive and developmental toxicity in animals and humans. The reference doses (RfD) of DBP and DEHP should be determined by sensitive endpoints. We here aimed to identify sensitive endpoints for DBP- and DEHP-induced such toxicity using published literatures. By examining the impacts of maternal exposure to DBP or DEHP on anogenital distance (AGD) and semen quality of offspring, we discovered that DBP or DEHP caused AGD decline in boys but increase in girls with DBP being more potent and the first 14weeks of pregnancy being more susceptible, suggesting a chemical- and time-dependent phenomenon. We also identified AGD shortening and total sperm count reduction as two sensitive endpoints for DBP- or DEHP-induced reproductive and developmental toxicity, respectively. Based upon these two endpoints and the employment of the Bayesian benchmark dose approach with an uncertainty factor of 3,000, we estimated the RfD values of DBP and DEHP were 15 μg/kg/day and 36 μg/kg/day, respectively. Thus, we uncover previously unrecognized phenomena of DBP- or DEHP-induced reproductive and developmental toxicity and establish new and comparable or more conservative RfDs for the risk assessment of phthalates exposure in humans. [Display omitted] • Total sperm count was a sensitive endpoint of maternal DBP exposure. • The anogenital distance was a sensitive endpoint of maternal DEHP exposure. • The recommended RfD for DBP is 15 μg/kg/day. • The proposed RfD for DEHP is 36 μg/kg/day. [ABSTRACT FROM AUTHOR]

Emerging findings point to a role for C1q/TNF-related protein 4 (CTRP4) in feeding in mammals. However, it remains unknown whether CTRP4 regulates feeding in fish. This study aimed to determine the feeding regulation function of CTRP4 in Siberian sturgeon (Acipenser baerii). In this study, the Siberian sturgeon ctrp4 (Abctrp4) gene was cloned, and Abctrp4 mRNA was shown to be highly expressed in the hypothalamus. In the hypothalamus, Abctrp4 mRNA decreased during fasting and reversed after refeeding. Subsequently, we obtained the AbCTRP4 recombinant protein by prokaryotic expression and optimized the expression and purification conditions. Siberian sturgeon (81.28 ± 14.75 g) were injected intraperitoneally using 30, 100, and 300 ng/g Body weight (BW) AbCTRP4 to investigate its effect on feeding. The results showed that 30, 100, and 300 ng/g BW of the AbCTRP4 significantly reduced the cumulative food intake of Siberian sturgeon at 1, 3, and 6 h. Finally, to investigate the potential mechanism of CTRP4 feeding inhibition, 300 ng/g BW AbCTRP4 was injected intraperitoneally. The findings demonstrated that AbCTRP4 treatment for 1 h significantly promoted the mRNA levels of anorexigenic peptides (pomc , cart , and leptin) while suppressing the mRNA abundances of orexigenic peptides (npy and agrp).In addition, the jak2/stat3 pathway in the hypothalamus was significantly activated after 1 h of AbCTRP4 treatment. In conclusion., this study confirms the anorexigenic effect of CTRP4 in Siberian sturgeon. [Display omitted] • Siberian sturgeon ctrp4 mRNA is highly expressed in the hypothalamus and is influenced by feeding status. • Intraperitoneal administration of prokaryotic expression of recombinant CTRP4 protein inhibited food intake at 1 h, 3 h and 6 h post injection in Siberian sturgeon. • Peripheral CTRP4 administration affected appetite factors mRNA expression in the hypothalamus and liver. • CTRP4 may affect Siberian sturgeon feeding through the jak2-stat3 signaling pathway. [ABSTRACT FROM AUTHOR]

FDA-approved anti-PD-L1 antibody drug Atezolizumab is a human IgG1 without glycosylation by an N297A mutation. Aglycosylation of IgG1 has been used to completely remove the unwanted Fc-mediated functions such as antibody-dependent cytotoxicity (ADCC). However, aglycosylated Atezolizumab is very unstable and easy to form aggregation, which causes quick development of anti-drug antibody (ADA) in 41% of Atezolizumab-treated cancer patients, eventually leading to loss of efficacy. Here, we report the development of the anti-PD-L1 antibody drug Maxatezo, a glycosylated version of Atezolizumab, with no ADCC activity, better thermo-stability, and significantly improved anti-tumor activity in vivo. Using Atezolizumab as the starting template, we back-mutated A297N to re-install the glycosylation, and inserted a short, flexible amino acid sequence (GGGS) between G237 and G238 in the hinge region of the IgG1 heavy chain. Our data shows that insertion of GGGS, does not alter the anti-PD-L1′s affinity and inhibitory activity, while completely abolishing ADCC activity. Maxatezo has a similar glycosylation profile and expression level (up to 5.4 g/L) as any normal human IgG1. Most importantly, Maxatezo's thermal stability is much better than Atezolizumab, as evidenced by dramatic increases of Tm1 from 63.55 °C to 71.01 °C and Tagg from 60.7 °C to 71.2 °C. Furthermore, the levels of ADA in mice treated with Maxatezo were significantly lower compared with animals treated with Atezolizumab. Most importantly, at the same dose (10 mg/kg), the tumor growth inhibition rate of Maxatezo was 98%, compared to 68% for Atezolizumab. [ABSTRACT FROM AUTHOR]

• A fully atomistic molecular dynamics model of bimodal atomic force microscopy is presented. • The double spring oscillator model can be used to represent the first two vibration modes of a cantilever beam. • It provides the possibility to observe the dynamic process of atomic interaction in bimodal AFM. Bimodal atomic force microscopy (AFM) is an important branch of multi-frequency AFM, which can simultaneously obtain the surface morphology and properties of samples. However, the atomic-scale phenomena in the vibration process of bimodal AFM have not been observed due to the absence of atomic-scale model. In this paper, the molecular dynamics (MD) simulations are used to model bimodal AFM. A double springs oscillator model is used to describe the first two vibration mode of the AFM cantilever. By applying dual-frequencies excitation, the dynamics of the model tip and the tip–substrate interactions are observed. The amplitude, phase shift and the average force change of the tip obtained in the simulation were found to be consistent with the continuum simulation results. The effect of different amplitude ratios on the vibration response of the tip is analyzed and validated by experiments. This novel model makes it possible to simulate two vibration modes of cantilever at atomic scale in bimodal AFM. [ABSTRACT FROM AUTHOR]

Laser frequency coupling noise due to unbalanced arm lengths is the dominant noise source for space-based gravitational wave detection. Time-delay interferometry is a proposed technique to eliminate the coupling noise by constructing a virtual equal-arm-length interferometer, where the real-time information of both absolute inter-satellite distance and clock synchronization is required. Inter-satellite laser ranging based on pseudo-random noise (PRN) sequence modulation has become the main technical means for extraction of the inter-satellite distance and clock difference information. This paper shows a bi-directional laser ranging scheme based on PRN code modulation and experimentally demonstrates its function by using an optical fiber of 10 km long. The measured results of the transmission time duration and the clock difference are compared with independent methods of pulse laser ranging and 1PPS signal measurement, respectively, both of which coincide well. It is also evaluated that the laser ranging accuracy is 1.2 m, and the clock synchronization accuracy reaches 6.7 ns, applicable to TianQin with the preliminarily determined requirement of 3 m and 10 ns. This laser ranging scheme can be applied to satellite navigation and space-based gravitational wave detection. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) of the knee is one of the main causes of mobility decline in the elderly. Non-surgical treatments such as administration of supplements to strengthen the joint cartilage matrix have become popular not only for pain relief but also for joint preservation. Glucosamine has been used in many countries based on the increasing evidence of its effectiveness for OA. Although there are many previous studies and systematic reviews, the findings vary and different conclusions have been drawn. We aimed to review recent randomized controlled trials on glucosamine for knee OA to reveal up-to-date findings about this supplement. We also performed a meta-analysis of some of the outcomes to overcome the unsolved bias in each study. Eighteen articles written between 2003 and 2016 were analyzed. Many used visual analogue scale (VAS) pain scores and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), which were assessed in our meta-analysis. We found a marginally favorable effect of glucosamine on VAS pain scores. The effect on knee function, as measured by the WOMAC, was small and not significant. A newly established knee OA scale, the Japanese Knee Osteoarthritis Measure (JKOM), is commonly used in Japan. Although the number of subjects was small, the JKOM meta-analysis indicated that glucosamine is superior to a placebo in alleviating knee OA symptoms. Given this, we concluded that glucosamine has the potential to alleviate knee OA pain. Further studies are needed to evaluate the effect of glucosamine on knee function and joint preservation, as well as to evaluate the combined effect with other components, such as chondroitin. [ABSTRACT FROM AUTHOR]

Abstract 4-Hydroxyisoleucine (4-HIL) exhibits a unique glucose-dependent insulinotropic activity and is a promising candidate for the treatment of diabetes. Direct fermentation of 4-HIL has been recently studied; however, the expected titre and yield were not achieved. In this study, we initially developed a pathway for the synthesis of 4-HIL in an L -isoleucine producer, C. glutamicum YI, but insufficient supply of α-ketoglutarate was a bottleneck for a strong production. Six genes involved in oxaloacetate and α-ketoglutarate branches were overexpressed or deleted, which increased the production of 4-HIL to 5.12 g/L but a considerable amount of L -isoleucine still accumulated in the culture. We then dynamically modulated the activity of the α-ketoglutarate dehydrogenase complex (ODHC) by employing L -isoleucine-responsive transcription or attenuation strategies. The best-engineered strain, HIL18, produced 34.21 g/L 4-HIL with a negligible accumulation of byproducts, including approximately 0.6 g/L L -isoleucine. This study achieved the highest production and yield of 4-HIL, and optimizing the TCA cycle by dynamically modulating the activity of ODHA can be a powerful strategy to balance the carbon flux and achieve efficient production of α-ketoglutarate and derivatives. Highlights • Corynebacterium glutamicum was used as chassis for 4-hydroxyisoleucine (4-HIL) fermentation. • Succinate synthesis coupled with L -isoleucine hydroxylation shunted the disrupted glyoxylate cycle and weakened TCA cycle. • TCA cycle was dynamically modulated to redistribute flux towards 4-HIL synthesis. • The highest 4-HIL production and yield via fermentation from glucose were achieved. [ABSTRACT FROM AUTHOR]

Galanin is a strong appetite promoting factor in mammals, but information about the mechanism of galanin in feeding regulation is very limited in fish. This study investigated the effects of galanin on food intake and explored the feeding regulation mechanism in Siberian sturgeon. Galanin and galanin receptor-3 (galr3) cDNA sequences of 557 bp and 710 bp were obtained respectively, and they were both abundantly expressed in the hypothalamus. Four experiments were performed to determine whether galanin affects food intake in Siberian sturgeon, including short-term fasting, intraperitoneal (i.p.) injection, and intraventricular (i.c.v.) injection. The results showed that galanin mRNA expression increased significantly after fasting for 1 (P < 0.05) and 3 h (P < 0.01). The galanin (0.50, 1.00, and 1.50 μg/g BW) i.p. injection did not significantly change food intake within 1, 3, or 6 h, but the galanin i.c.v. injection concentrations of 0.01, 0.05, and 0.10 μg/g BW significantly increased food intake within 3 h (P < 0.01, P < 0.05, P < 0.001, respectively). An i.c.v. co-injection experiment with galanin and spexin was carried out to further explore the mechanism of galanin on the feeding regulation and to clarify the relationship between galanin and spexin. The results showed that 0.20 μg/g BW spexin significantly reversed the appetite promoting effect of 0.10 μg/g BW galanin (P < 0.05). Moreover, galanin did not affect the expression of galr3 , while spexin significantly decreased the transcriptional level of galr3 (P < 0.05). The expression of nine appetite factors (cart , ucn3 , apelin , nucb2 , npy , cck , galanin , spexin , and pyy), significantly changed among the four groups (saline, galanin, spexin, and galanin + spexin). These results indicate that central galanin promotes food intake, which may have been mediated by the detected down-regulating anorexic signals including cart , ucn3 , and pyy in the hypothalamus. Spexin reduced appetite, probably related to the upregulation of cart and ucn3 transcript expression and down-regulation of npy. This investigation provides a theoretical basis for an in-depth analysis of the feeding regulation mechanism in teleost. • Galanin and its receptor-3 sequences and tissue expression patterns were obtained. • After short-term fasting, galanin mRNA level increased in the hypothalamus. • i.p. injection did not affect the food intake, but i.c.v. injection did. • 0.20 μg/g BW spexin reversed the appetite promoting effect of 0.10 μg/g BW galanin. • The levels of appetite factors were changed among Spexin or Galanin injection groups. [ABSTRACT FROM AUTHOR]

5, Atezolizumab induced high titers of ADA in mice, in good agreement with what was observed in monkeys (100%) and cancer patients (41.5%). In the Abstract section, "However, aglycosylated Atezolizumab is very unstable and easy to form aggregation, which causes quick development of anti-drug antibody (ADA) in 41% of Atezolizumab-treated cancer patients, eventually leading to loss of efficacy" now reads: "However, aglycosylated Atezolizumab is unstable and easy to form aggregates." 5, Atezolizumab induced extremely high titers of ADA in mice, in good agreement with what was observed in monkeys (100%) and cancer patients (41.5%). [Extracted from the article]

Highlights: [•] Film thickness plays an important role in the preferred orientation of CuAlO2 films. [•] The electrical conductivity increases with increasing film thickness. [•] The band gap decreases with increasing film thickness. [•] The biggest of the figure of merit is achieved for the sample with the thickness around 165nm. [Copyright &y& Elsevier]

Abstract: Poloidal Field (PF) coils, made of CICC (Cable-In-Conduit Conductors), are the most important part of ITER (International Thermonuclear Experimental Reactor) superconducting magnet system. The structure of superconducting magnet system in ITER and the CICC are introduced. The main factors influenced the cabling of the superconducting cable for CICC is discussed. Analyzed the outer diameter controlling technique and the relationship between ac loss and structure parameters of the superconducting cable. The technique route of cabling has been established. Especially, the technique of dies setting for shaping+multi-rolling compacting dies+half-dies for diameter keeping is explained in detail, which can efficiently control the diameter and the cabling quality of the superconducting cable, without injury to strands line. The technical parameters for cabling is fixed and one 765m long dummy cable and one 115m long superconducting cable of CICC for PF coil is manufactured successfully for ITER the last. [Copyright &y& Elsevier]

• A non-induced and non-auxotrophic E. coli for homoserine synthesis was obtained. • Degradation of homoserine was dynamically attenuated rather than blocked. • Efflux of homoserine was precisely modulated by promoter optimization. l -Homoserine is a valuable non-proteinogenic amino acid used in the synthesis of various important compounds. Microbial fermentation has potential value for producing l -homoserine on a large scale, but suffers from a low yield and the need for expensive additives. In this study, a non-induced, non-auxotrophic, plasmid-free Escherichia coli chassis for the high-efficiency production of l -homoserine was constructed. Initially, the l -homoserine degradation pathway was dynamically attenuated. Subsequently, systems metabolic engineering strategies were employed, including reinforcing the synthetic flux, improving NADPH generation, and elevating l -homoserine efflux. The constructed strain HOM-14, produced 60.1 g/L l -homoserine without additional supplements or inducers, which achieved the highest fermentative production efficiency of l -homoserine till date. Moreover, common byproducts, such as acetate, did not accumulate. The strategies presented here can be applied in the further engineering of chassis for the scale-up production of l -homoserine and derivatives. [ABSTRACT FROM AUTHOR]

Periodontitis is a highly prevalent disease that damages the supporting tissues of a tooth, including the alveolar bone. Alveolar bone loss owing to periodontitis is broadly categorized as supra-alveolar and intra-alveolar bone loss. In intra-alveolar bone loss, the defect has an angular or oblique orientation to the long axis of the tooth in an apical direction. In contrast, the defect is perpendicular to the long axis of the tooth in supra-alveolar bone loss. Unlike intra-alveolar bone defects, supra-alveolar bone defects lack supporting adjacent space, which makes supra-alveolar bone regeneration more challenging. In addition, the limited availability of resources in terms of vascularity and underlying tissues is another obstacle to supra-alveolar bone regeneration. Currently, supra-alveolar bone loss is the least predictable periodontal defect type in regenerative periodontal therapy. In addition, supra-alveolar bone loss is much more common than other alveolar bone loss. Despite its prevalence, research on supra-alveolar bone regeneration remains sparse, indicating an unmet need for significant research efforts in this area. This review summarize recent advances, obstacles, and future directions in the field of supra-alveolar bone regeneration. We discuss the biomaterials, bioactive molecules, and cells that have been tested for supra-alveolar bone regeneration, followed by pre-clinical and clinical approaches employed in this field. Additionally, we highlight obstacles and present future directions that will propel supra-alveolar bone research forward., Competing Interests: Declaration of competing interest The authors declare that they do not have any competing financial or personal interests that could influence the work reported in this paper. Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Purpose: To analyze the characteristics of optical coherence tomography in acute macular neuroretinopathy (AMN) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and discuss the prognostic predictors., Methods: Patients with AMN following SARS-CoV-2 infection were divided into two groups according to the presence or absence of hyperreflective outer nuclear layer (ONL) lesion involving the fovea., Results: The first visit included 14 eyes in the fovea-involved group and 20 eyes in the no fovea-involved group. Ellipsoid zone (EZ) hyporeflection and interdigitation zone (IZ) interruption were detected in all eyes. Other common manifestations were myoid zone (MZ) hyperreflection (76.5%), ONL hyperreflection (73.5%), outer plexiform layer (OPL) thickening (64.7%), and EZ interruption (50%). The follow-up period was 48.4 ± 55.3 days. At the last visit, 12 eyes were in the fovea-involved group and 13 eyes in the no fovea-involved group. IZ interruption was detected in all eyes. Other common manifestations were EZ hyporeflection (92.0%), ONL atrophy (40.0%), OPL thickening (36.0%), OPL linear (32.0%), and MZ hyperreflection (32%). The improvement of visual acuity (VA) was -0.5 ± 0.5 and -0.2 ± 0.4 in the fovea-involved group and the no fovea-involved group, respectively, with a statistically significant difference between them (P = 0.045). Initial VA, initial cotton wool spot, initial ONL cyst, final ONL cyst, and final OPL linear were associated with final VA (P = 0.000, P = 0.029, P = 0.044, P = 0.049, P = 0.049, respectively)., Conclusions: In the early stage of AMN following SARS-CoV-2 infection, IZ interruption and EZ hyporeflection were the most common manifestations, and pathology of IZ was more serious than that of EZ. Subsequently, OPL and ONL atrophied, and ONL atrophied faster. Regardless of whether hyperreflective ONL involved the fovea, VA improved, with a more noticeable improvement found in the fovea-involved group. The presence of initial ONL cyst and initial cotton wool spot, rapid atrophy of OPL, and poorer initial VA indicating poorer VA outcome., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Objective: This study aimed to search and analyze relevant evidence on perioperative activities in patients undergoing hepatectomy and provide a summary of the best evidence available., Methods: Comprehensive computer searches were conducted in various databases, including PubMed, Cochrane Library, BMJ Best Practice, Joanna Briggs Institute, Evidence-Based Health Care Centre Database, US Guidelines Network, UK National Institute of Clinical Medicine, Scottish Intercollegiate Guidelines Network, International Guidelines Association Network, New Zealand Clinical Practice Guidelines Network, and Chinese Biomedical Literature Database from January 30, 2022 to December 30, 2023. The search included guidelines, expert consensus, evidence summaries, systematic reviews, and original research closely related to the evidence., Results: A total of 11 pieces of evidence were included, consisting of 2 guidelines, 2 expert consensuses, 1 evidence summary, 1 systematic review, and 5 randomized controlled trials (RCTs). From these, five pieces of best evidence were identified., Conclusions: The evidence from the included studies collectively indicates that well-planned perioperative activities are safe and beneficial for patients undergoing hepatectomy. Furthermore, high-quality local guidelines have been established in China, suggesting that healthcare professionals can adopt these practices to accelerate patient recovery and enhance the quality of clinical care.

Background: The Oxidative Balance Score (OBS) is a systematic tool to assess the effects of diet and lifestyle in relation to oxidative stress. The association between OBS and gout has not been reported previously. We conducted a cross-sectional study to investigate the complex association between OBS and gout in US adults., Methods: In all, 10 492 participants were included in this study. The exposure variable was OBS, which was scored by 16 dietary and four lifestyle factors. Multivariate logistic regression, subgroup analysis, and restricted cubic spline (RCS) regression were used to analyze the association between OBS and gout., Results: Compared with the lowest OBS quartile group (Q1), the multivariate corrected odds ratio (OR) (95% confidence interval [C]) for the highest quartile of OBS (Q4) was 0.72 (0.52-1.00) (p = .13 for trend); furthermore, the RCS showed a negative linear relationship between OBS and gout (p-nonlinear = .606)., Conclusion: In conclusion, the risk of gout is higher with high OBS. The prevalence of gout decreased with higher OBS. Diabetes may alter this negative correlation., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Compressive sensing (CS) can reconstruct the rest information almost without distortion by advanced computational algorithm, which significantly simplifies the process of atomic force microscope (AFM) scanning with high imaging quality. In common CS-AFM, the partial measurements randomly come from the whole region to be measured, which easily leads to detail loss and poor image quality in regions of interest (ROIs). Consequently, important microscopic phenomena are missed probably. In this paper, we developed an adaptive under-sampling strategy for CS-AFM to optimize the process of sampling. Under a certain under-sampling ratio, the weight coefficient of ROIs and regions of base (ROBs) were set to control the distribution of under-sampling points and corresponding measurement matrix. A series of simulations were completed to demonstrate the relationship between the weight coefficient of ROIs and image quality. After that, we verified the effectiveness of the method on our homemade AFM. Through a lot of simulations and experiments, we demonstrated how the proposed method optimized the sampling process of CS-AFM, which speeded up the process of AFM imaging with high quality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Multifrequency atomic force microscopy (AFM) utilizes the multimode operation of cantilevers to achieve rapid high-resolution imaging and extract multiple properties. However, the higher-order modal response of traditional rectangular cantilever is weaker in air, which affects the sensitivity of multifrequency AFM detection. To address this issue, we previously proposed a bridge/cantilever coupled system model to enhance the higher-order modal response of the cantilever. This model is simpler and less costly than other enhancement methods, making it easier to be widely used. However, previous studies were limited to theoretical analysis and preliminary simulations regarding ideal conditions. In this paper, we undertake a more comprehensive investigation of the coupled system, taking into account the influence of probe and excitation surface sizes on the modal response. To facilitate the exploration of the effectiveness and optimal conditions for the coupled system in practical applications, a macroscale experimental platform is established. By conducting finite element analysis and experiments, we compare the performance of the coupled system with that of traditional cantilevers and quantify the enhancement in higher-order modal response. Also, the optimal conditions for the enhancement of macroscale cantilever modal response are explored. Additionally, we also supplement the characteristics of this model, including increasing the modal frequency of the original cantilever and generating additional resonance peaks, demonstrating the significant potential of the coupled system in various fields of AFM., (Copyright © 2024, Sun et al.)

Background: Epstein-Barr virus (EBV) is a double-stranded DNA oncogenic virus. Several types of solid tumors, such as nasopharyngeal carcinoma, EBV-associated gastric carcinoma, and lymphoepithelioma-like carcinoma of the lung, have been linked to EBV infection. Currently, several TCR-T-cell therapies for EBV-associated tumors are in clinical trials, but due to the suppressive immune microenvironment of solid tumors, the clinical application of TCR-T-cell therapy for EBV-associated solid tumors is limited. Figuring out the mechanism by which EBV participates in the formation of the tumor immunosuppressive microenvironment will help T cells or TCR-T cells break through the limitation and exert stronger antitumor potential., Methods: Flow cytometry was used for analyzing macrophage differentiation phenotypes induced by EBV-infected and EBV-uninfected tumors, as well as the function of T cells co-cultured with these macrophages. Xenograft model in mice was used to explore the effects of M2 macrophages, TCR-T cells, and matrix metalloprotein 9 (MMP9) inhibitors on the growth of EBV-infected tumors., Results: EBV-positive tumors exhibited an exhaustion profile of T cells, despite the presence of a large T-cell infiltration. EBV-infected tumors recruited a large number of mononuclear macrophages with CCL5 and induced CD163+M2 macrophages polarization through the secretion of CSF1 and the promotion of autocrine IL10 production by mononuclear macrophages. Massive secretion of MMP9 by this group of CD163+M2 macrophages induced by EBV infection was an important factor contributing to T-cell exhaustion and TCR-T-cell therapy resistance in EBV-positive tumors, and the use of MMP9 inhibitors improved the function of T cells cocultured with M2 macrophages. Finally, the combination of an MMP9 inhibitor with TCR-T cells targeting EBV-positive tumors significantly inhibited the growth of xenografts in mice., Conclusions: MMP9 inhibitors improve TCR-T cell function suppressed by EBV-induced M2 macrophages. TCR-T-cell therapy combined with MMP9 inhibitors was an effective therapeutic strategy for EBV-positive solid tumors., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Gastrin is an important intragastrointestinal hormone, but reports on its regulation of feeding behavior in fish are still scarce. This study aimed to determine the feeding regulatory function of gastrin in sturgeon. In this study, a gastrin/cholecystokinin-like peptide was identified in the genomes of sturgeon and proved to be gastrin by evolutionary tree analysis. Tissue distribution of gastrin and its receptor, cholecystokinin receptor B (CCKRB), showed that both had high mRNA abundance in the hypothalamus and gastrointestinal tract. In the duodenum, gastrin and CCKRB mRNAs were reduced at 1 h of fasting, and both were also observed in the stomach and hypothalamus in response to changes in feeding status. Sulfated gastrin 17 is the major form of gastrin in vivo. Therefore, we investigated the effect of sulfated gastrin 17 on feeding by intraperitoneal injection into Siberian sturgeon using sulfated gastrin 17. The results showed that gastrin 17 significantly reduced the cumulative feeding of Siberian sturgeon in the short term (1, 3 and 6 h) and long term (1, 2, 3, 4, 5 and 7 days). Finally, we explored the potential mechanism of feeding inhibition after intraperitoneal injection of gastrin 17 for 7 consecutive days. The results showed that gastrin 17 treatment significantly increased the mRNA levels of anorexigenic peptides (cart, cck and pyy), while it had no significant effect on the mRNA abundance of orexigenic peptides (npy and agrp). In addition, gastrin 17 treatment significantly affected the expression of appetite signaling pathways in the hypothalamus, such that the mRNA expression of ampkα1 was significantly reduced, whereas the mRNA abundance of stat3, mtor and s6k was significantly increased. In conclusion, the present study confirmed the anorectic effect of gastrin on Siberian sturgeon., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Botulinum toxin type A (BTA) is becoming more and more prevalent as an injection agent in cosmetic surgery. However, there is an increasing amount of cases reporting unexpected adverse reactions related to BTA injection. BTA can invoke many kinds of hypersensitive reactions, some of which can be delayed-type or even fatal; hence, it is of crucial importance to pay close attention to atypical and early symptoms that may indicate the presence of BTA allergy in patients., Methods: In this study, we reported three cases of mild and unexpected BTA-related hypersensitive reaction with a symptom of nonpruritic erythema on the chest that happened after BTA treatment of upper facial wrinkles and proposed several suggestions based on our practical experience and literature review., Results: Two patients' symptoms were alleviated spontaneously, and one patient's were alleviated after taking oral corticosteroid. According to our literature review, we believe that these incidences indicate a kind of unreported allergic reaction relevant to botulinum toxin., Conclusions: We suggest clinicians consider warily patients' subsequent BTA injection schedule if any suspicious reaction occurs after treatment. We suggest that patients who experience nonpruritic erythema after botulinum toxin injection should suspend subsequent injection plans for at least 3 months to prevent more severe consequences., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: Nonalcoholic fatty liver disease (NAFLD) stands a prevalent chronic liver condition significantly influenced by oxidative stress. We investigated the unclear relationship between antioxidant-rich diet and lifestyle and cardiovascular disease (CVD) prevalence rate and mortality in adult patients with NAFLD., Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHAENS) spanning from 1999 to 2018 to investigate the association between adherence to an antioxidant-rich diet and lifestyle and the cardiovascular disease (CVD) prevalence rate and mortality in adult patients with NAFLD. The study employed the Oxidative Balance Score (OBS) to define antioxidant diet and lifestyle., Results: Including 8,670 adult patients with NAFLD, the study revealed an inverse association between OBS and the prevalence of most CVD conditions. Fully adjusted models demonstrated that each unit increase in diet OBS, lifestyle OBS, and overall OBS corresponded to a 2, 7, and 2% reduction in all-cause mortality, respectively. In models 2, findings revealed that lifestyle Q2 and Q3 were linked to reduced cancer mortality, whereas diet and overall OBS did not exhibit an association. Additionally, Stratified analysis revealed that age (<45 years) and education level (> high school) significantly influenced the association between the OBS and the prevalence of CVD., Conclusion: These results underscore the protective link between adherence to an antioxidant diet and lifestyle and a diminished prevalence of CVD and mortality in adults with NAFLD, particularly among younger and higher-educated populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li and Liu.)

Motilin is a gastrointestinal hormone that is mainly produced in the duodenum of mammals, and it is responsible for regulating appetite. However, the role and expression of motilin are poorly understood during starvation and the weaning stage, which is of great importance in the seeding cultivation of fish. In this study, the sequences of Yangtze sturgeon ( Acipenser dabryanus Motilin ( AdMotilin )) motilin receptor ( AdMotilinR ) were cloned and characterized. The results of tissue expression showed that by contrast with mammals, AdMotilin mRNA was richly expressed in the brain, whereas AdMotilinR was highly expressed in the stomach, duodenum, and brain. Weaning from a natural diet of T. Limnodrilus to commercial feed significantly promoted the expression of AdMotilin in the brain during the period from day 1 to day 10, and after re-feeding with T. Limnodrilus the change in expression of AdMotilin was partially reversed. Similarly, it was revealed that fasting increased the expression of AdMotilin in the brain (3 h, 6 h) and duodenum (3 h), and the expression of AdMotilinR in the brain (1 h) in a time-dependent manner. Furthermore, it was observed that peripheral injection of motilin-NH 2 increased food intake and the filling index of the digestive tract in the Yangtze sturgeon, which was accompanied by the changes of AdMotilinR and appetite factors expression in the brain ( POMC , CART , AGRP , NPY and CCK ) and stomach ( CCK ). These results indicate that motilin acts as an indicator of nutritional status, and also serves as a novel orexigenic factor that stimulates food intake in Acipenser dabryanus . This study lays a strong foundation for the application of motilin as a biomarker in the estimation of hunger in juvenile Acipenser dabryanu during the weaning phase, and enhances the understanding of the role of motilin as a novel regulator of feeding in fish.

Cinnabar is the naturally occurring mercuric sulfide (HgS) and concerns about its safety have been grown. However, the molecular mechanism of HgS-related neurotoxicity remains unclear. S-phase kinase-associated protein 1 (Skp1), identified as the target protein of HgS, plays a crucial role in the development of neurological diseases. This study aims to investigate the neurotoxic effects and molecular mechanism of HgS based on Skp1 using the Caenorhabditis elegans (C. elegans) model. We prepared the HgS nanoparticles and conducted a comparative analysis of neurobehavioral differences in both wild-type C. elegans (N2) and a transgenic strain of C. elegans (VC1241) with a knockout of the SKP1 homologous gene after exposure to HgS nanoparticles. Our results showed that HgS nanoparticles could suppress locomotion, defecation, egg-laying, and associative learning behaviors in N2 C. elegans, while no significant alterations were observed in the VC1241 C. elegans. Furthermore, we conducted a 4D label-free proteomics analysis and screened 504 key proteins significantly affected by HgS nanoparticles through Skp1. These proteins play pivotal roles in various pathways, including SNARE interactions in vesicular transport, TGF-beta signaling pathway, calcium signaling pathway, FoxO signaling pathway, etc. In summary, HgS nanoparticles at high doses suppress the neurobehavioral functions of C. elegans through a Skp1-dependent mechanism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Nasopharyngeal carcinoma (NPC) is a malignant tumor that originates in the nasopharyngeal mucosa and is common in China and Southeast Asian countries. Cancer cells reprogram glycolytic metabolism to promote their growth, survival and metastasis. Glycolysis plays an important role in NPC development, but the underlying mechanisms remain incompletely elucidated. Lactate dehydrogenase A (LDHA) is a crucial glycolytic enzyme, catalyzing the last step of glycolysis. This study aims to investigate the exact role of LDHA, which catalyzes the conversion of pyruvate into lactate, in NPC development., Methods and Results: The western blot and immunohistochemical (IHC) results indicated that LDHA was significantly upregulated in NPC cells and clinical samples. LDHA knockdown by shRNA significantly inhibited NPC cell proliferation and invasion. Further knockdown of LDHA dramatically weakened the tumorigenicity of NPC cells in vivo. Mechanistic studies showed that LDHA activated TGF-β-activated kinase 1 (TAK1) and subsequent nuclear factor κB (NF-κB) signaling to promote NPC cell proliferation and invasion. Exogenous lactate supplementation restored NPC cell proliferation and invasion inhibited by LDHA knockdown, and this restorative effect was reversed by NF-κB inhibitor (BAY 11-7082) or TAK1 inhibitor (5Z-7-oxozeaenol) treatment. Moreover, clinical sample analyses showed that LDHA expression was positively correlated with TAK1 Thr187 phosphorylation and poor prognosis., Conclusions: Our results suggest that LDHA and its major metabolite lactate drive NPC progression by regulating TAK1 and its downstream NF-κB signaling, which could become a therapeutic target in NPC., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)