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Purpose: Achieving a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT) remains a challenge for most patients with rectal cancer. Exploring the potential of combining NCRT with immunotherapy or targeted therapy for those achieving a partial response (PR) offers a promising avenue to enhance treatment efficacy. This study investigated the impact of NCRT on the tumor microenvironment in locally advanced rectal cancer (LARC) patients who exhibited a PR. Methods: This was a retrospective, observational study. Five patients demonstrating a PR after neoadjuvant treatment for LARC were enrolled in the study. Biopsy samples before treatment and resected specimens after treatment were stained with a panel of 26 antibodies targeting various immune and tumor-related markers, each labeled with distinct metal tags. The labeled samples were then analyzed using the Hyperion imaging system. Results: Heterogeneity within the tumor microenvironment was observed both before and after NCRT. Notably, tumor-associated macrophages, CD4 + T cells, CD8 + T cells, CD56 + natural killer cells, tumor-associated neutrophils, cytokeratin, and E-cadherin exhibited slight increase in abundance within the tumor microenvironment following treatment (change ratios = 0.78, 0.2, 0.27, 0.32, 0.17, 0.46, 0.32, respectively). Conversely, the number of CD14 + monocytes, CD19 + B cells, CD45 + CD4 + T cells, collagen I, α-smooth muscle actin, vimentin, and β-catenin proteins displayed significant decreases post-treatment (change ratios = 1.73, 1.92, 1.52, 1.25, 1.52, 1.12, 2.66, respectively). Meanwhile, Foxp3 + regulatory cells demonstrated no significant change (change ratio = 0.001). Conclusions: NCRT has diverse effects on various components of the tumor microenvironment in LARC patients who achieve a PR after treatment. Leveraging combination therapies may optimize treatment outcomes in this patient population. [ABSTRACT FROM AUTHOR]

Two families of room temperature vulcanized PDMS with different hardness were thermally aged. Mechanical properties were monitored by tensile tests, and macromolecular architecture was followed by differential scanning calorimetry (crystallization) and sol–gel analysis (swelling degree). Data showed that PDMS display a loss of plasticity due to a crosslinking process. The main novelty was to describe mechanical behaviour by a hyperelastic so-called Ogden's model whose coefficients were correlated with macromolecular properties and then ageing degree. The model coefficients were also used to derive an embrittlement criterion. [ABSTRACT FROM AUTHOR]

BOADICEA is a comprehensive risk prediction model for breast and/or ovarian cancer (BC/OC) and for carrying pathogenic variants (PVs) in cancer susceptibility genes. In addition to BRCA1 and BRCA2, BOADICEA version 6 includes PALB2, CHEK2, ATM, BARD1, RAD51C and RAD51D. To validate its predictions for these genes, we conducted a retrospective study including 2033 individuals counselled at clinical genetics departments in Denmark. All counselees underwent comprehensive genetic testing by next generation sequencing on suspicion of hereditary susceptibility to BC/OC. Likelihoods of PVs were predicted from information about diagnosis, family history and tumour pathology. Calibration was examined using the observed-to-expected ratio (O/E) and discrimination using the area under the receiver operating characteristics curve (AUC). The O/E was 1.11 (95% CI 0.97–1.26) for all genes combined. At sub-categories of predicted likelihood, the model performed well with limited misestimation at the extremes of predicted likelihood. Discrimination was acceptable with an AUC of 0.70 (95% CI 0.66–0.74), although discrimination was better for BRCA1 and BRCA2 than for the other genes in the model. This suggests that BOADICEA remains a valid decision-making aid for determining which individuals to offer comprehensive genetic testing for hereditary susceptibility to BC/OC despite suboptimal calibration for individual genes in this population. [ABSTRACT FROM AUTHOR]

Genetic variants in cell division cycle 42 (CDC42) can manifest with dysmorphic features, autoinflammation, hemophagocytic lymphohistiocytosis, and thrombocytopenia, whereas defective thymopoiesis is a rare disease manifestation. We report a novel CDC42 missense variant (c.46A > G, p.Lys16Glu) resulting in infection and HPV-driven carcinogenesis in the mosaic mother and impaired thymopoiesis and profound T cell lymphopenia in the heterozygous daughter identified through newborn screening for SCID. We found that surface expression of IL-7Rα (CD127) was decreased, consistent with reduced IL-7-induced STAT5 phosphorylation and accelerated apoptotic T cell death. Consistent with the vital role of IL-7 in regulating thymopoiesis, both patients displayed reduced T cell receptor CDR3 repertoires. Moreover, the CDC42 variant prevented binding to the downstream effector, p21-activated kinase (PAK)1, suggesting this impaired interaction to underlie reduced IL-7Rα expression and signaling. Here, we provide the first report of severely compromised thymopoiesis and perturbed IL-7Rα signaling caused by a novel CDC42 variant and presenting with diverging clinical and immunological phenotypes in patients. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) play key roles in colorectal cancer (CRC) progression, but little is known about the biological functions of hsa_circRNA_001676 in CRC. Therefore, we explored the potential role of hsa_circRNA_001676 in CRC development. RT-qPCR was performed to determine hsa_circRNA_001676, miR-556-3p and Ras-GTPase-activating SH3 domain-binding-proteins 2 (G3BP2) levels in CRC tissues. Meanwhile, to evaluate the roles of hsa_circRNA_001676, miR-556-3p and G3BP2 on CRC, functional analysis of cell proliferation, migration and stemness were then performed. Our results showed that compared to normal tissues, hsa_circRNA_001676 and G3BP2 level was elevated, but miR-556-3p level was reduced in CRC tissues. Additionally, luciferase reporter results showed that hsa_circRNA_001676 was shown to target miR-556-3p, and G3BP2 was targeted by miR-556-3p. Hsa_circRNA_001676 or G3BP2 overexpression promoted CRC cell proliferation and migration. Conversely, miR-556-3p overexpression suppressed CRC cell proliferation and migration. Moreover, deficiency of hsa_circRNA_001676 or G3BP2 repressed the CRC cell proliferation, migration and stemness. Meanwhile, hsa_circRNA_001676 deficiency obviously reduced tumor growth and stemness in a CRC mouse xenograft model. Furthermore, hsa_circRNA_001676 deficiency notably reduced G3BP2 level, but elevated miR-556-3p level in tumor tissues from tumor-bearing mice. Mechanistically, hsa_circRNA_001676 targeted miR-556-3p to increase G3BP2 level, contributing to the progression of CRC. Collectively, hsa_circRNA_001676 was able to accelerate proliferation, migration and stemness in CRC through regulating miR-556-3p/G3BP2 axis, suggesting that hsa_circRNA_001676 may become a potential therapeutic target in treating CRC. [ABSTRACT FROM AUTHOR]

Twin rotors concentric face-gear power-split transmission system (TRCFGPSTS) is a new and more advanced main reducer configuration of the high-speed helicopter. Its load-sharing performance between different branches has a great impact on the service life performance. Its load distribution is complex, and the research on the influence law of error on load-sharing performance is not clear. Therefore, to study the influence of system error and pinions floating on the mechanical properties of the system, the static load-sharing mathematical model of the system was established. The load-sharing model comprehensively considers the factors of manufacturing error (ME) and installation error (IE), meshing stiffness, torsional stiffness, support stiffness and member floating. The coordination conditions of torsional angle elastic deformation of the system with central displacement offset and the mechanical balance conditions under the action of elastic support and floating support are derived, which reflects the change law of load distribution from the perspective of the system as a whole. The load-sharing model is solved by the least square method. The load-sharing coefficient (LSC) of the system is obtained. The influence of ME, IE and floating pinions on load-sharing performance is analyzed. The results show that the LSC shows irregular periodic fluctuation under the combined action of error, and the LSC is 1.212. Under the single influence of ME, the LSC also shows irregular periodic fluctuation, and the LSC is 1.610. Under the single influence of IE, the LSC presents a constant influence law, and the LSC is 1.326. The error of each gear in the III-stage has the most obvious influence on the load-sharing characteristics. The LSC of I-stage and II-stage floating pinion under the single influence are 1.113 and 1.120, respectively. The floating gear can significantly improve the load-sharing performance, and meet the load-sharing at the ±5 % service requirement. [ABSTRACT FROM AUTHOR]

Outbreaks of zoonotic diseases are accelerating at an unprecedented rate in the current era of globalization, with substantial impacts on the global economy, public health, and sustainability. Alien species invasions have been hypothesized to be important to zoonotic diseases by introducing both existing and novel pathogens to invaded ranges. However, few studies have evaluated the generality of alien species facilitating zoonoses across multiple host and parasite taxa worldwide. Here, we simultaneously quantify the role of 795 established alien hosts on the 10,473 zoonosis events across the globe since the 14th century. We observe an average of ~5.9 zoonoses per alien zoonotic host. After accounting for species-, disease-, and geographic-level sampling biases, spatial autocorrelation, and the lack of independence of zoonosis events, we find that the number of zoonosis events increase with the richness of alien zoonotic hosts, both across space and through time. We also detect positive associations between the number of zoonosis events per unit space and climate change, land-use change, biodiversity loss, human population density, and PubMed citations. These findings suggest that alien host introductions have likely contributed to zoonosis emergences throughout recent history and that minimizing future zoonotic host species introductions could have global health benefits. Alien species invasions are thought to be important to zoonotic diseases through the introduction of both existing and novel pathogens to invaded ranges. Using data from 795 established alien animals and 10,473 zoonosis events worldwide, this study examines the role of alien zoonotic hosts on zoonosis emergences after accounting for climate, propagule pressure, global change and sampling bias. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is one of the most common devastating injuries, with little possibility of recovery in humans. However, zebrafish efficiently regenerate functional nervous system tissue after SCI. Therefore, the spinal cord transection model of adult zebrafish was applied to explore the role of ATF6 in neuro-recovery. Activating transcription factor 6 (ATF6) is a type-II transmembrane protein in the endoplasmic reticulum (ER). ATF6 target genes could improve ER homeostasis, which contributes to cytoprotection. Herein, we found that the ATF6 level increased at 12 h and 3 days post SCI, and returned to sham levels at 7 days post SCI. ATF6-expressing motor neurons were present in the central canal of the spinal cord and increased at 12 h post SCI. ATF6 morpholino treatment showed that inhibition of ATF6 delayed locomotor recovery and hindered neuron axon regrowth in SCI zebrafish. Furthermore, we investigated the role of both binding immunoglobulin protein (Bip) and C/EBP homologous transcription factor protein (CHOP), the two target genes of ATF6. We found that Bip expression significantly increased in the spinal cord at 7 days after SCI, which served as a pro-survival chaperone. Our results also showed that CHOP expression significantly decreased in the spinal cord at 7 days after SCI, which was identified as a protein involved in apoptosis. Taken together, our data demonstrate that ATF6 may contribute to the functional recovery after SCI in adult zebrafish, via up-regulation of Bip and down-regulation of CHOP to restore the homeostasis of ER. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a functional impairment of the spinal cord caused by external forces, accompanied by limb movement disorders and permanent paralysis, which seriously lowers the life quality of SCI patients. Secondary injury caused by inflammation attenuated the therapeutic effects of SCI. Therefore, the exploration of biomarkers associated with the inflammatory response following SCI might provide novel therapy strategy against SCI.SCI rat model was established as previously reported and evaluated by BBB score. The expression of microRNA-24-3p (miR-24-3p) and MAPK-activated protein kinase 2 (MK2) in spinal cord tissues of SCI rats and HAPI cells was analyzed by qRT-PCR. Protein expression of MK2, ionized calcium-binding adapter molecule-1 (Iba-1), tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β) was assessed by western blot assay. The release of inflammatory cytokines TNF-α and IL-1β was measured by enzyme-linked immunosorbent assay (ELISA). The interaction between miR-24-3p and MK2 was examined by the luciferase reporter system. Basso-Beattie-Bresnahan (BBB) score dramatically reduced in rats following SCI compared with sham rats. Moreover, the expression of miR-24-3p was down-regulated, while MK2 was up-regulated in the spinal cord tissues of SCI rats and LPS-induced microglia cells compared with the corresponding control group. Luciferase reporter system confirmed the interaction between miR-24-3p and MK2. In addition, miR-24-3p upregulation or MK2 knockdown attenuated LPS induced activation of microglial cells and expression of inflammatory cytokine TNF-α and IL-1β. Besides, we discovered that miR-24-3p regulated inflammation of highly aggressively proliferating immortalized (HAPI) cells by targeting MK2.In our study, we clarified that miR-24-3p repressed inflammation of microglia cells following SCI by regulating MK2, thereby providing promising biomarkers for SCI therapy. [ABSTRACT FROM AUTHOR]

This correction notice is for an article titled "Validation of the BOADICEA model for predicting the likelihood of carrying pathogenic variants in eight breast and ovarian cancer susceptibility genes." The correction addresses errors in the results section and table 3 of the original article. The errors have been corrected, and the original article has been updated. The authors of the article are Nanna Bæk Møller, Desirée Sofie Boonen, Elisabeth Simone Feldner, Qin Hao, Martin Larsen, Anne‑Vibeke Lænkholm, Åke Borg, Anders Kvist, Therese Törngren, Uffe Birk Jensen, Susanne Eriksen Boonen, Mads Thomassen, and Thorkild Terkelsen. [Extracted from the article]

Digital patternless freeze-casting technology is a new approach for obtaining frozen sand moulds using digital milling technology. The change law of tensile strength and air permeability of frozen sand moulds (100-mesh and 200-mesh silica sand, and zircon sand moulds) under different freezing temperatures and water contents was studied. Results show that with the decrease of freezing temperature and the increase of water contents, the tensile strength and air permeability of the sand moulds are gradually improved. Meanwhile, computed tomography technology was used to characterize the shape and size of the water film between the sand particles mixed with 4wt.% water. The results show that in silica sand moulds, the form of water film is lumpy, and 200-mesh silica sand moulds have more water films and higher proportion of small-sized water films than 100-mesh silica sand moulds, while in zircon sand moulds, the form of water film is membranous. At the same freezing temperature and water content, the tensile strength of zircon sand mould is the highest, and 100-mesh silica sand mould is the lowest. A comparative solidification experiment of A356 aluminum alloy was carried out in frozen sand mould and resin sand mould. The results show that the primary a-Al phase appears in the form of equiaxed and eutectic silicon phase is needle-like in freezing sand mould casting, but the primary a-Al phase grows in the form of dendrites, and the eutectic silicon phase is coarse needle-like in the resin sand mould casting. The difference of microstructure is caused by the different cooling rate. The cooling rate of A356 aluminum alloy in frozen sand mould is higher than that in resin sand mould. [ABSTRACT FROM AUTHOR]

Thirty surface sediments and three sediment cores were collected from mangrove wetlands in the Pearl River Estuary of South China to investigate the spatial and vertical distribution of Dechlorane Plus (DP). DP concentrations in the mangrove surface sediments ranged from 0.0130 to 1.504 ng/g dry weight (dw). DP concentrations in sediments from Shenzhen were significantly greater than those from Guangzhou and Zhuhai. Anti-Cl-DP, the dechlorinated product of anti-DP, was also detected in the mangrove sediments with concentrations ranged from not detected to 0.0198 ng/g dw. Significant positive relationship between anti-Cl-DP and anti-DP levels was observed in the mangrove sediments, suggesting that photo and/or microbial degradation of anti-DP might occur in the sediments. The f values in the mangrove sediments were close to those in the technical DP products, suggesting that stereoselective enrichment of anti-DP may not exist in the mangrove sediments. DP concentrations in the mangrove sediment cores generally showed an increasing trend from the bottom to top layers. This is the first study to report the occurrence of DP and its degradation product in the mangrove wetlands. [ABSTRACT FROM AUTHOR]

The influences of the four different surface dipole sources in a centrifugal pump on the acoustic calculating accuracy are studied in this paper, by using the CFD combined with the Lighthill acoustic analogy methods. Firstly, the unsteady flow in the pump is solved based on the large eddy simulation method and the pressure pulsations on the four different surfaces are obtained. The four surfaces include the volute surface, the discharge pipe surface, the inner surface of the pump cavity, and the interfaces between the impeller and the stationary parts as well as the outer surface of the impeller. Then, the software Sysnoise is employed to interpolate the pressure fluctuations onto the corresponding surfaces of the acoustic model. The Fast Fourier Transform with a Hanning window is used to analyze the pressure fluctuations and transform them into the surface dipole sources. The direct boundary element method is applied to calculate the noise radiated from the dipole sources. And the predicted sound pressure level is compared with the experimental data. The results show that the pressure fluctuations on the discharge pipe surface and the outer surface of the impeller have little effect on the acoustic simulation results. The pressure pulsations on the inner surface of the pump cavity play an important role in the internal flow and the acoustic simulation. The acoustic calculating error can be reduced by about 7% through considering the effect of the pump cavity. The sound pressure distributions show that the sound pressure level increases with the growing flow rate, with the largest magnitude at the tongue zone. [ABSTRACT FROM AUTHOR]

We established a catalog of the mouse gut metagenome comprising ∼2.6 million nonredundant genes by sequencing DNA from fecal samples of 184 mice. To secure high microbiome diversity, we used mouse strains of diverse genetic backgrounds, from different providers, kept in different housing laboratories and fed either a low-fat or high-fat diet. Similar to the human gut microbiome, >99% of the cataloged genes are bacterial. We identified 541 metagenomic species and defined a core set of 26 metagenomic species found in 95% of the mice. The mouse gut microbiome is functionally similar to its human counterpart, with 95.2% of its Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologous groups in common. However, only 4.0% of the mouse gut microbial genes were shared (95% identity, 90% coverage) with those of the human gut microbiome. This catalog provides a useful reference for future studies. [ABSTRACT FROM AUTHOR]

Optical interferometers comprising birefringent-crystal beam displacers, wave plates, and phase shifters serve as stable devices for simulating quantum information processes such as heralded coined quantum walks. Quantum walks are important for quantum algorithms, universal quantum computing circuits, quantum transport in complex systems, and demonstrating intriguing nonlinear dynamical quantum phenomena. We introduce fully controllable polarization-independent phase shifters in optical pathes in order to realize site-dependent phase defects. The effectiveness of our interferometer is demonstrated through realizing single-photon quantum-walk dynamics in one dimension. By applying site-dependent phase defects, the translational symmetry of an ideal standard quantum walk is broken resulting in localization effect in a quantum walk architecture. The walk is realized for different site-dependent phase defects and coin settings, indicating the strength of localization signature depends on the level of phase due to site-dependent phase defects and coin settings and opening the way for the implementation of a quantum-walk-based algorithm. [ABSTRACT FROM AUTHOR]

l-Lactic acid production by Lactobacillus casei was used as a model to study the mechanism of substrate inhibition and the strategy for enhancing l-lactic acid production. It was found that the concentration of cell growth and l-lactate decreased with the increase of glucose concentration and fermentation temperature. To enhance the osmotic stress resistance of the strain at high temperature, a mutant G-03 was screened and selected with 360 g/L glucose at 45°C as the selective criterion. To further increase the cell growth for lactic acid production, 3 g/L of biotin was supplemented to the medium. As a result, l-lactate concentration by the mutant G-03 reached 198.2 g/L (productivity of 5.5 g L h) at 41°C in a 7-L fermentor with 210 g/L glucose as carbon source. l-Lactate concentration and productivity of mutant G-03 were 115.2% and 97.8% higher than those of the parent strain, respectively. The strategy for enhancing l-lactic acid production by increasing osmotic stress resistance at high temperature may provide an alternative approach to enhance organic acid production with other strains. [ABSTRACT FROM AUTHOR]

Nanoplatelets of metal oxides with interesting porous structure were obtained by thermal treatment of Ni/Al hydrotalcite. Structural and surface properties of the porous oxides were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM and HRTEM), and N2 adsorption–desorption. The electrochemical performance of the electrodes was investigated by cyclic voltammetry, electrochemical impedance spectroscopy and constant current charge–discharge measurements. Ni/Al hydrotalcite calcined at 450 °C (NA-450) displayed a maximum specific capacitance (419.0 F g−1) due to the porous structure with the highest specific surface area (142.3 m2 g−1) and small pore size (4.4 nm). The present study shows the potential of NiO nanoplatelets composite material for electrochemical pseudo-capacitors. [ABSTRACT FROM AUTHOR]

Twenty-four soil samples of eight ecosystem-types around the Yellow River source area were investigated for the number and specific composition of soil dematiaceous hyphomycetes by dilution plate technique. And then the co-relationship between genus species of soil dematiaceous hyphomycetes and ecosystem-types was analyzed. The results show that the amount and species distribution of soil dematiaceous hyphomycetes had an obvious variability in different ecosystem-types, and that the dominant genus species varied in the eight ecosystem-types studied, with Cladosporium being the dominant genus in seven of the eight ecosystem-types except wetland. The index of species diversity varied in different ecosystem-types. The niche breadth analysis showed that Cladosporium had the highest niche breadth and distributed in all ecosystem-types, while the genera with a narrow niche breadth distributed only in a few ecosystem-types. The results of niche overlap index analysis indicated that Stachybotrys and Torula, Doratomyces and Scolecobasidium, Cladosporium and Chrysosporium had a higher niche overlap, whereas Arthrinium and Gliomastix, Phialophora and Doratomyces, Oidiodendron and Ulocladium had no niche overlap. [ABSTRACT FROM AUTHOR]