Changes of Development from Childhood to Late Adulthood in Rats Tracked by Urinary Proteome.

To date, studies of development have mainly focused on the embryonic stage and a short time thereafter. There has been little research on the whole life of an individual from childhood to aging and death. For the first time, we used noninvasive urinary proteome technology to track changes in several important developmental time points in a group of rats, covering 10 time points from childhood, adolescence, young adulthood, middle adulthood, and near-death in old age. Similar to previous studies on puberty, proteins were detected and they are involved in sexual or reproductive maturation, mature spermatozoa in seminiferous tubules (first seen), gonadal hormones, decline of estradiol, brain growth, and central nervous system myelination, and our differential protein enrichment pathways also included reproductive system development, tube development, response to hormone, response to estradiol, brain development, and neuron development. Similar to previous studies in young adults, proteins were detected and they are involved in musculoskeletal maturity, peak bone mass, development of the immune system, and growth and physical development, and our differential proteins enrichment pathways also included skeletal system development, bone regeneration, system development, immune system processes, myeloid leukocyte differentiation, and developmental growth. Studies on aging-related changes in neurons and neurogenesis have been reported, and we also found relevant pathways in aged rats, such as regulation of neuronal synaptic plasticity and positive regulation of long-term neuronal synaptic plasticity. However, at all time points throughout life, there were many biological pathways revealed by differential urinary protein enrichment involving multiple organs, tissues, systems, etc. that have not been mentioned in existing studies. This study shows comprehensive and detailed changes in rat lifetime development through the urinary proteome, helping to fill the gap in development research. Moreover, it provides a new approach to monitoring changes in human health and diseases of aging using the urinary proteome.

Spatiotemporally mapping temperature dynamics of lysosomes and mitochondria using cascade organelle-targeting upconversion nanoparticles.

The intracellular metabolism of organelles, like lysosomes and mitochondria, is highly coordinated spatiotemporally and functionally. The activities of lysosomal enzymes significantly rely on the cytoplasmic temperature, and heat is constantly released by mitochondria as the byproduct of adenosine triphosphate (ATP) generation during active metabolism. Here, we developed temperature-sensitive LysoDots and MitoDots to monitor the in situ thermal dynamics of lysosomes and mitochondria. The design is based on upconversion nanoparticles (UCNPs) with high-density surface modifications to achieve the exceptionally high sensitivity of 2.7% K-1 and low uncertainty of 0.8 K for nanothermometry to be used in living cells. We show the measurement is independent of the ion concentrations and pH values. With Ca2+ ion shock, the temperatures of both lysosomes and mitochondria increased by ∼2 to 4 °C. Intriguingly, with chloroquine (CQ) treatment, the lysosomal temperature was observed to decrease by up to ∼3 °C, while mitochondria remained relatively stable. Lastly, with oxidative phosphorylation inhibitor treatment, we observed an ∼3 to 7 °C temperature increase and a thermal transition from mitochondria to lysosomes. These observations indicate different metabolic pathways and thermal transitions between lysosomes and mitochondria inside HeLa cells. The nanothermometry probes provide a powerful tool for multimodality functional imaging of subcellular organelles and interactions with high spatial, temporal, and thermal dynamics resolutions.

Large-Area Near-Infrared Emission Enhancement on Single Upconversion Nanoparticles by Metal Nanohole Array.

Single lanthanide (Ln) ion doped upconversion nanoparticles (UCNPs) exhibit great potential for biomolecule sensing and counting. Plasmonic structures can improve the emission efficiency of single UCNPs by modulating the energy transferring process. Yet, achieving robust and large-area single UCNP emission modulation remains a challenge, which obstructs investigation and application of single UCNPs. Here, we present a strategy using metal nanohole arrays (NHAs) to achieve energy-transfer modulation on single UCNPs simultaneously within large-area plasmonic structures. By coupling surface plasmon polaritons (SPPs) with higher-intermediate state (1D2 → 3F3, 1D2 → 3H4) transitions, we achieved a remarkable up to 10-fold enhancement in 800 nm emission, surpassing the conventional approach of coupling SPPs with an intermediate ground state (3H4 → 3H6). We numerically simulate the electrical field distribution and reveal that luminescent enhancement is robust and insensitive to the exact location of particles. It is anticipated that the strategy provides a platform for widely exploring applications in single-particle quantitative biosensing.

Yersinia ruckeri Infection and Enteric Redmouth Disease among Endangered Chinese Sturgeons, China, 2022.

During October 2022, enteric redmouth disease (ERM) affected Chinese sturgeons at a farm in Hubei, China, causing mass mortality. Affected fish exhibited characteristic red mouth and intestinal inflammation. Investigation led to isolation of a prominent bacterial strain, zhx1, from the internal organs and intestines of affected fish. Artificial infection experiments confirmed the role of zhx1 as the pathogen responsible for the deaths. The primary pathologic manifestations consisted of degeneration, necrosis, and inflammatory reactions, resulting in multiple organ dysfunction and death. Whole-genome sequencing of the bacteria identified zhx1 as Yersinia ruckeri, which possesses 135 drug-resistance genes and 443 virulence factor-related genes. Drug-susceptibility testing of zhx1 demonstrated high sensitivity to chloramphenicol and florfenicol but varying degrees of resistance to 18 other antimicrobial drugs. Identifying the pathogenic bacteria associated with ERM in Chinese sturgeons establishes a theoretical foundation for the effective prevention and control of this disease.

Ferroelectricity in hafnia controlled via surface electrochemical state.

Ferroelectricity in binary oxides including hafnia and zirconia has riveted the attention of the scientific community due to the highly unconventional physical mechanisms and the potential for the integration of these materials into semiconductor workflows. Over the last decade, it has been argued that behaviours such as wake-up phenomena and an extreme sensitivity to electrode and processing conditions suggest that ferroelectricity in these materials is strongly influenced by other factors, including electrochemical boundary conditions and strain. Here we argue that the properties of these materials emerge due to the interplay between the bulk competition between ferroelectric and structural instabilities, similar to that in classical antiferroelectrics, coupled with non-local screening mediated by the finite density of states at surfaces and internal interfaces. Via the decoupling of electrochemical and electrostatic controls, realized via environmental and ultra-high vacuum piezoresponse force microscopy, we show that these materials demonstrate a rich spectrum of ferroic behaviours including partial-pressure-induced and temperature-induced transitions between ferroelectric and antiferroelectric behaviours. These behaviours are consistent with an antiferroionic model and suggest strategies for hafnia-based device optimization.

Interleukin-26 in channel catfish (Ictalurus punctatus): Molecular characterization and immune functional activity.

IL-26 is a crucial inflammatory cytokine that participates in defending host cells against infections. We initially cloned and identified the cDNA sequences of interleukin (IL)-26 in channel catfish (Ictalurus punctatus). The open reading frame (ORF) of IpIL-26 was 537 bp in length, encoding 178 amino acids (aa). Constitutive expression of IpIL-26 was observed in tested tissues, with the highest level found in the gill and spleen. To explore the function of IpIL-26 in channel catfish, different stimuli were used to act on both channel catfish and channel catfish kidney cells (CCK). The expression of IpIL-26 could be up-regulated by bacteria and viruses in multiple tissues. In vitro, recombinant IpIL-26 (rIpIL-26) could induce the expression levels of inflammatory cytokines such as TNF-α, IL-1ß, IL-6, IL-20, and IL-22 playing vital roles in defending the host against infections. Our results demonstrated that IpIL-26 might be an essential cytokine, significantly affecting the immune defense of channel catfish against pathogen infections.

Effects of dietary succinic acid supplementation on growth performance, digestive ability, intestinal development and immunity of large yellow croaker (Larimichthys crocea) larvae.

The application of artificial micro-diet is an effective way to improve and standardize the quality of aquatic animal larvae. However, the widespread adoption of micro-diet faces a bottleneck due to the limited utilization capacity of the larvae. A 30-day feeding experiment was carried out to investigate the effect of dietary succinic acid (SA) on the growth performance, digestive ability, intestinal development, and immunity of large yellow croaker larvae (initial body weight 11.33 ± 0.57 mg). Four isonitrogenous and isolipidic diets were formulated, incorporating 0.00%, 0.01%, 0.02% and 0.03% SA separately. The results showed that a diet with 0.02% SA significantly increased both the final body weight and the specific growth rate of the larvae. Regarding digestive ability, 0.01% SA supplementation significantly enhanced trypsin activity in both intestinal and pancreatic segments. In addition, 0.01% SA supplementation notably improved amylase activity in the intestinal segment, while diets with 0.01%-0.02% SA significantly improved lipase activity in the pancreatic segment. In terms of intestinal development, 0.01% SA supplementation remarkably boosted the activities of alkaline-phosphatase and leucine-aminopeptidase on brush border membrane in intestine. Furthermore, 0.03% SA supplementation significantly increased the expression of occludin. In terms of immunity, larvae fed diets with 0.01%-0.02% SA exhibited significantly higher lysozyme activity compared to the control group. Supplementation with 0.01% SA also significantly increased both iNOS activity and NO content. In summary, the findings of this study suggested that adding 0.02% SA can improve the growth performance of large yellow croaker larvae by improving digestive enzymes activities, promoting intestinal development, and enhancing nonspecific immunity.

Effects of dietary supplementation with heat-killed Lactobacillus acidophilus on growth performance, digestive enzyme activity, antioxidant capacity, and inflammatory response of juvenile large yellow croaker (Larimichthys crocea).

A ten-week culture trial in juvenile large yellow croaker (Larimichthys crocea) (10.80 ± 0.10 g) was conducted to assess the impact of supplementing heat-killed Lactobacillus acidophilus (HLA) on growth performance, intestinal digestive enzyme activity, antioxidant capacity and inflammatory response. Five iso-nitrogenous (42 % crude protein) and iso-lipidic (12 % crude lipid) experimental feeds with different levels of HLA (0.0 %, 0.1 %, 0.2 %, 0.4 %, or 0.8 %) were prepared. They were named FO (control group), HLA0.1, HLA0.2, HLA0.4 and HLA0.8, respectively. The results indicated that HLA addition had no impact on survival (P > 0.05). In this experiment, the final body weight, weight gain rate and specific growth rate showed a quadratic regression trend, initially increasing and subsequently decreasing with the increasing in HLA levels, and attained the peak value at 0.2 % HLA supplemental level (P < 0.05). In contrast to the control group, in terms of digestive ability, amylase, lipase and trypsin exhibited a notable linear and quadratic pattern, demonstrating a substantial increase when 0.1% 0.2 % HLA was added in the diets (P < 0.05). Notably, elevated levels of catalase (CAT) activity, superoxide dismutase (SOD) activity, and total antioxidant capacity (T-AOC) were observed in the liver when adding 0.1%-0.2 % HLA, and the level of malondialdehyde (MDA) was significantly decreased and the liver exhibited a notable upregulation in the mRNA expression levels of nrf2, cat, sod2, and sod3 (P < 0.05). Additionally, the mRNA levels of genes associated with tight junctions in the intestines (zo-1, zo-2 and occludin) exhibited a significant upregulation when 0.2 % HLA was added in the feed (P < 0.05). Furthermore, the levels of mRNA expression for proinflammatory genes in the intestines including tnf-α, il-1ß, il-6 and il-8 exhibited a quadratic regression trend, characterized by an initial decline followed by subsequent growth (P < 0.05). Meanwhile, the levels of mRNA expression for genes linked to anti-inflammatory responses in the intestines (including il-10, tgf-ß, and arg1) exhibited a quadratic regression pattern, initially increasing and subsequently decreasing (P < 0.05). Compare with the control group, the levels of tnf-α, il-1ß and il-8 expression were notably downregulated in all HLA addition groups (P < 0.05). When 0.2 % HLA was added, the expression levels of il-10, tgf-ß and arg1 in the intestinal tract were markedly increased (P < 0.05). Overall, the supplementation of 0.2 % HLA in the feed has been shown to enhance the growth performance. The enhancement was attributed to HLA's capacity to improve antioxidant function, intestinal barrier integrity, and mitigate inflammatory responses. This research offers a scientific foundation for the utilization of HLA in aquaculture.

Mechanism of sturgeon intestinal inflammation induced by Yersinia ruckeri and the effect of florfenicol intervention.

The mechanism by which Y. ruckeri infection induces enteritis in Chinese sturgeon remains unclear, and the efficacy of drug prevention and control measures is not only poor but also plagued with numerous issues. We conducted transcriptomic and 16 S rRNA sequencing analyses to examine the differences in the intestinal tract of hybrid sturgeon before and after Y. ruckeri infection and florfenicol intervention. Our findings revealed that Y. ruckeri induced the expression of multiple inflammatory factors, including il1ß, il6, and various chemokines, as well as casp3, casp8, and multiple tumor necrosis factor family members, resulting in pathological injury to the body. Additionally, at the phylum level, the relative abundance of Firmicutes and Bacteroidota increased, while the abundance of Plesiomonas and Cetobacterium decreased at the genus level, altering the composition of the intestinal flora. Following florfenicol intervention, the expression of multiple apoptosis and inflammation-related genes was down-regulated, promoting tissue repair. However, the flora became further dysregulated, increasing the risk of infection. In conclusion, our analysis of the transcriptome and intestinal microbial composition demonstrated that Y. ruckeri induces intestinal pathological damage by triggering apoptosis and altering the composition of the intestinal microbiota. Florfenicol intervention can repair pathological damage, but it also exacerbates flora imbalance, leading to a higher risk of infection. These findings help elucidate the molecular mechanism of Y. ruckeri-induced enteritis in sturgeon and evaluate the therapeutic effect of drugs on intestinal inflammation in sturgeon.

Dynamic Failure Experimental Study of a Gravity Dam Model on a Shaking Table and Analysis of Its Structural Dynamic Characteristics.

Investigating the dynamic response patterns and failure modes of concrete gravity dams subjected to strong earthquakes is a pivotal area of research for addressing seismic safety concerns associated with gravity dam structures. Dynamic shaking table testing has proven to be a robust methodology for exploring the dynamic characteristics and failure modes of gravity dams. This paper details the dynamic test conducted on a gravity dam model on a shaking table. The emulation concrete material, featuring high density, low dynamic elastic modulus, and appropriate strength, was meticulously designed and fabricated. Integrating the shaking table conditions with the model material, a comprehensive gravity dam shaking table model test was devised to capture the dynamic response of the model under various dynamic loads. Multiple operational conditions were carefully selected for in-depth analysis. Leveraging the dynamic strain responses, the progression of damage in the gravity dam model under these diverse conditions was thoroughly examined. Subsequently, the recorded acceleration responses were utilized for identifying dynamic characteristic parameters, including the acceleration amplification factor in the time domain, acceleration response spectrum characteristics in the frequency domain, and modal parameters reflecting the inherent characteristics of the structure. To gain a comprehensive understanding, a comparative analysis was performed by aligning the observed damage development with the identified dynamic characteristic parameters, and the sensitivity of these identified parameters to different levels of damage was discussed. The findings of this study not only offer valuable insights for conducting and scrutinizing shaking table experiments on gravity dams but also serve as crucial supporting material for identifying structural dynamic characteristic parameters and validating damage diagnosis methods for gravity dam structures.

On-Chip Mirror Enhanced Multiphoton Upconversion Super-Resolution Microscopy.

Multiphoton upconversion super-resolution microscopy (MPUM) is a promising imaging modality, which can provide increased resolution and penetration depth by using nonlinear near-infrared emission light through the so-called transparent biological window. However, a high excitation power is needed to achieve emission saturation, which increases phototoxicity. Here, we present an approach to realize the nonlinear saturation emission under a low excitation power by a simply designed on-chip mirror. The interference of the local electromagnetic field can easily confine the point spread function to a specific area to increase the excitation efficiency, which enables emission saturation under a lower excitation power. With no additional complexity, the mirror assists to decrease the excitation power by 10-fold and facilities the achievement of a lateral resolution around 35 nm, 1/28th of the excitation wavelength, in imaging of a single nanoparticle on-chip. This method offers a simple solution for super-resolution enhancement by a predesigned on-chip device.

LPS stimulation stabilizes HIF-1α by enhancing HIF-1α acetylation via the PARP1-SIRT1 and ACLY-Tip60 pathways in macrophages.

Hypoxia and inflammatory mediators stabilize hypoxia-inducible factor (HIF)-1α through posttranslational modifications, such as phosphorylation and succinylation. Here, we identified sirtuin 1 (SIRT1) and 60 kDa Tat-interactive protein (Tip60)-mediated acetylation as another critical posttranslational modification that regulates HIF-1α protein stability under lipopolysaccharide (LPS) stimulation. Mechanistically, DNA damage induced by excessive reactive oxygen species (ROS) activated poly (ADP-ribose) polymerase 1 (PARP1) to consume oxidized nicotinamide adenine dinucleotide (NAD+ ). Correspondingly, SIRT1 activity was decreased with the decline in NAD+ levels, resulting in increased HIF-1α acetylation. LPS also activated the ATP-citrate lyase (ACLY)-Tip60 pathway to further enhance HIF-1α acetylation. Acetylation contributed to HIF-1α stability and exacerbated LPS-induced inflammation. Thus, inhibiting HIF-1α stability by decreasing its acetylation could partly alleviate LPS-induced inflammation. In conclusion, we revealed the mechanism by which LPS stabilized HIF-1α by increasing its acetylation via the PARP1-SIRT1 and ACLY-Tip60 pathways in fish macrophages. This study may provide novel insights for manipulation of HIF-1α acetylation as a therapeutic strategy against inflammation from the perspective of acetylation in vertebrates.

Effects of diets rich in Agaricus bisporus polysaccharides on the growth, antioxidant, immunity, and resistance to Yersinia ruckeri in channel catfish.

To promote the application of Agaricus bisporus polysaccharides (ABPs) in channel catfish (Ictalurus punctatus) culture, we evaluated the effects of ABPs on the growth, immunity, antioxidant, and antibacterial activity of channel catfish. When the amount of ABPs was 250 mg/kg, channel catfish's weight gain and specific growth rates increased significantly while the feed coefficient decreased. We also found that adding ABPs in the feed effectively increased the activities of ACP, MDA, T-SOD, AKP, T-AOC, GSH, and CAT enzymes and immune-related genes such as IL-1ß, Hsp70, and IgM in the head kidney of channel catfish. Besides, long-term addition will not cause pathological damage to the head kidney. When the amount of ABPs was over 125 mg/kg, the protection rate of channel catfish was more than 60%. According to the intestinal transcriptome analysis, the addition of ABPs promoted the expression of intestinal immunity genes and growth metabolism-related genes and enriched multiple related KEEG pathways. When challenged by Yersinia ruckeri infection, the immune response of channel catfish fed with ABPs was intenser and quicker. Additionally, the 16S rRNA gene sequencing analysis showed that the composition of the intestinal microbial community of channel catfish treated with ABPs significantly changed, and the abundance of microorganisms beneficial to channel catfish growth, such as Firmicutes and Bacteroidota increased. In conclusion, feeding channel catfish with ABPs promoted growth, enhanced immunity and antioxidant, and improved resistance to bacterial infections. Our current results might promote the use of ABPs in channel catfish and even other aquacultured fish species.

Effect of Agaricus bisporus Polysaccharides (ABPs) on anti-CCV immune response of channel catfish.

Herein, the effects of Agaricus bisporus Polysaccharides (ABPs) on anti-channel catfish virus (CCV) infections to promote their application in channel catfish culture were explored. Transcriptome and metabolome analyses were conducted on the spleen of a CCV-infected channel catfish model fed with or without ABPs. CCV infections upregulated many immune and apoptosis-related genes, such as IL-6, IFN-α3, IFN-γ1, IL-26, Casp3, Casp8, and IL-10, and activated specific immunity mediated by B cells. However, after adding ABPs, the expression of inflammation-related genes decreased in CCV-infected channel catfish, and the inflammatory inhibitors NLRC3 were upregulated. Meanwhile, the expression of apoptosis-related genes was reduced, indicating that ABPs can more rapidly and strongly enhance the immunity of channel catfish to resist viral infection. Moreover, the metabonomic analysis showed that channel catfish had a high energy requirement during CCV infection, and ABPs could enhance the immune function of channel catfish. In conclusion, ABPs can enhance the antiviral ability of channel catfish by enhancing immune response and regulating inflammation. Thus, these findings provided new insights into the antiviral response effects of ABPs, which might support their application in aquaculture.

Neem oil against Aeromonas hydrophila infection by disrupting quorum sensing and biofilm formation.

Aeromonas hydrophila is an opportunistic pathogen that can cause a number of infectious diseases in fish and is widely distributed in aquatic environments. Antibiotics are the main approach against A. hydrophila infections, while the emergence of resistant bacteria limits the application of antibiotics. Here, quorum-sensing (QS) was defined as the target and the inhibitory effects of neem oil against QS of A. hydrophila was studied. The results showed that neem oil could dose-dependently reduce aerolysin, protease, lipase, acyl-homoserine lactones (AHLs), biofilm and swarming motility at sub-inhibitory concentrations. Results of real-time PCR demonstrated that neem oil could down-regulate the transcription of aerA, ahyI and ahyR. Moreover, neem oil showed significant protections to A549 cells and a fish infection model. Taken together, these results indicated that neem oil could be chosen as a promising candidate for the treatment of A. hydrophila infections.

The feasibility of a new self-guided pedicle tap for pedicle screw placement: an anatomical study.

PURPOSE: To investigate the safety and accuracy of applying a new self-guided pedicle tap to assist pedicle screw placement. METHODS: A new self-guided pedicle tap was developed based on the anatomical and biomechanical characteristics of the pedicle. Eight adult spine specimens, four males and four females, were selected and tapped on the left and right sides of each pair of T1-L5 segments using conventional taps (control group) and new self-guided pedicle taps (experimental group), respectively, and pedicle screws were inserted. The screw placement time of the two groups were recorded and compared using a stopwatch. The safety and accuracy of screw placement were observed by CT scanning of the spine specimens and their imaging results were graded according to the Heary grading criteria. RESULTS: Screw placement time of the experimental group were (5. 73 ± 1. 18) min in thoracic vertebrae and (5. 09 ± 1. 31) min in lumbar vertebrae respectively. Screw placement time of the control group were respectively (6. 02 ± 1. 54) min in thoracic vertebrae and (5.51 ± 1.42) min in lumbar vertebrae. The difference between the two groups was not statistically significant (P > 0. 05). The Heary grading of pedicle screws showed 112 (82.35%) Heary grade I screws and 126 (92.65%) Heary grade I + II screws in the experimental group, while 96 (70.59%) Heary grade I screws and 112 (82.35%) Heary grade I + II screws in the control group.The difference between the two groups was statistically significant (P < 0.05). CONCLUSION: The new self-guided pedicle tap can safely and accurately place thoracic and lumbar pedicle screws with low-cost and convenient procedure,which indicates a good clinical application value.

Correlations of IL-6 and TGF-ß Gene Polymorphisms and Expressions With Osteoporotic, Thoracolumbar, Vertebral Compression Fracture.

Context: Associations between genes and diseases manifest as the influence of gene expression on disease development as well as the impact of variations in the disease-related genes themselves. It's important to determine the genetic variations that can lead to compressed fractures of osteoporotic, thoracic lumbar vertebrae to develop personalized clinical methods to prevent or delay the disease's development. Objective: The study intended to explore the correlations between the gene polymorphisms and gene expressions of the interleukin-6 (IL-6) gene and the transforming growth factor-beta (TGF-ß) gene and osteoporotic, thoracolumbar, vertebral compression fracture. Design: The research team performed an observational study using data from medical records. Setting: The study took place at Xuzhou Medical University in Xuzhou, China. Participants: Participants were 200 patients with an osteoporotic, thoracolumbar, vertebral compression fracture who had been admitted to the hospital at the university between 2019 and 2021 prior to the study and 200 healthy people The research team divided the participants into two groups. The patients became participants in the disease group, and the healthy individuals became participants in the control group. Outcome Measures: The research team: (1) collected peripheral blood from the two groups, (2) extracted genomic deoxyribonucleic acids (DNAs) from karyocytes, (3) examined the IL-6 and TGF-ß gene polymorphisms, and (4) analyzed and correlated participants' clinical data with the gene polymorphisms and expressions. The team used a quantitative polymerase chain reaction (qPCR) to examine the expression levels of IL-6 and TGF-ß. Results: Compared to the control group, the disease group: (1) had allele distributions that were significantly different at the rs2069829 locus of the IL-6 gene (P < .001) and at the rs3087453 of the TGF-ß gene (P = .004); (2) had significantly higher frequencies of allele T at the rs2069829 locus of the IL-6 gene and of allele G at the rs3087453 locus of the TGF-ß gene; (3) had genotype distributions that were significantly different at the rs2069829 locus (P < .001) and the rs2069857 locus (P = .048) of the IL-6 gene and at the rs3087453 locus (P < .001) of the TGF-ß gene; (4) had frequencies that were significantly higher of the TT genotype at the rs2069829 locus, the CC genotype at the rs2069857 locus, and the GC genotype at the rs3087453 locus of the IL-6 gene and the TGF-ß gene; (5) had dominant models that were significantly different at the rs2069829 locus of the IL-6 gene (P = .009) and at rs3087453 locus of the TGF-ß gene (P = .026) and had a recessive model that was significantly different at the rs2069857 locus of the IL-6 gene (P = .040); (6) had significantly different haplotypes CC (P < .001) and TC (P < .001) at the rs2069829 locus and the rs2069857 locus of the IL-6 gene and a significantly different haplotype AC (P = .011) at the rs1800469 locus and the rs3087453 locus of the TGF-ß gene; (7) had an IL-6 gene polymorphism at the rs2069857 locus that was related to the expression of the IL-6 gene (P < .05) and an expression of the IL-6 gene for participants with the AA genotype that was significantly lower than for other genotypes; (8) had a TGF-ß gene polymorphism at the rs1800469 locus that was associated with the expression of the TGF-ß gene (P < .05), and an expression for participants with the GG genotype that was significantly higher than for other genotypes; (9) had an IL-6 gene polymorphism at the rs2069857 locus with an overt correlation with the genotype of osteoporotic, thoracolumbar, vertebral compression fracture (P < .001). Also, participants in the disease group with the genotype CC mainly had type 2 and 3 fractures, while those with genotype AA primarily had type 0 and 1 fractures. Conclusions: IL-6 and TGF-ß gene polymorphisms and expressions are significantly related to osteoporotic, thoracolumbar, vertebral compression fracture.

Efficacy analysis of minimally invasive surgery for Raynaud's syndrome.

BACKGROUND: Raynaud's syndrome (RS), also referred to as Raynaud's phenomenon, is a vasospastic disorder causing episodic color changes in extremities upon exposure to cold or stress. These manifestations, either primary Raynaud's phenomenon (PRP) or associated with connective tissue diseases like systemic sclerosis (SSc) as secondary Raynaud's phenomenon (SRP), affect the quality of life. Current treatments range from calcium channel blockers to innovative surgical interventions, with evolving efficacy and safety profiles. METHODS: In this retrospective study, patients diagnosed with RS were selected based on complete medical records, ensuring homogeneity between groups. Surgeries involved microscopic excision of sympathetic nerve fibers and stripping of the digital artery's adventitia. Postoperative care included antibiotics, analgesia, oral nifedipine, and heat therapies. Evaluation metrics such as the VAS pain score and RCS score were collected bi-weekly. Data analysis was conducted using SPSS 26.0, with significance set at p < 0.05. RESULTS: In total, 15 patients formed the experimental group, with five presenting fingertip soft tissue necrosis and ten showing RS symptoms. Comparative analysis of demographic data between experimental and control groups, both containing 15 participants, demonstrated no significant age and gender difference. However, the "Mean Duration of RP attack" in the experimental group was notably shorter (9.47 min ± 0.31) than the control group (19.33 min ± 1.79). The RS Severity Score also indicated milder severity for the experimental cohort (score: 8.55) compared to the control (score: 11.23). Postoperative assessments at 2, 4, and 6 weeks revealed improved VAS pain scores, RCS scores, and other measures for the experimental group, showing significant differences (p < 0.05). One distinctive case showcased a variation in the common digital nerve and artery course in an RS patient. CONCLUSION: Our retrospective analysis on RS patients indicates that microsurgical techniques are safe and effective in the short term. As surgical practices lean towards minimally invasive methods, our data supports this shift. However, extensive, prospective studies are essential for conclusive insights.

Single Small Extracellular Vesicle (sEV) Quantification by Upconversion Nanoparticles.

Cancer-derived small extracellular vesicles (sEVs) are potential circulating biomarkers in liquid biopsies. However, their small sizes, low abundance, and heterogeneity in molecular makeups pose major technical challenges for detecting and characterizing them quantitatively. Here, we demonstrate a single-sEV enumeration platform using lanthanide-doped upconversion nanoparticles (UCNPs). Taking advantage of the unique optical properties of UCNPs and the background-eliminating property of total internal reflection fluorescence (TIRF) imaging technique, a single-sEV assay recorded a limit of detection 1.8 × 106 EVs/mL, which was nearly 3 orders of magnitude lower than the standard enzyme-linked immunosorbent assay (ELISA). Its specificity was validated by the difference between EpCAM-positive and EpCAM-negative sEVs. The accuracy of the UCNP-based single-sEV assay was benchmarked with immunomagnetic-beads flow cytometry, showing a high correlation (R2> 0.99). The platform is suitable for evaluating the heterogeneous antigen expression of sEV and can be easily adapted for biomarker discoveries and disease diagnosis.

Exploiting Dynamic Nonlinearity in Upconversion Nanoparticles for Super-Resolution Imaging.

Single-beam super-resolution microscopy, also known as superlinear microscopy, exploits the nonlinear response of fluorescent probes in confocal microscopy. The technique requires no complex purpose-built system, light field modulation, or beam shaping. Here, we present a strategy to enhance this technique's spatial resolution by modulating excitation intensity during image acquisition. This modulation induces dynamic optical nonlinearity in upconversion nanoparticles (UCNPs), resulting in variations of nonlinear fluorescence response in the obtained images. The higher orders of fluorescence response can be extracted with a proposed weighted finite difference imaging algorithm from raw fluorescence images to generate an image with higher resolution than superlinear microscopy images. We apply this approach to resolve single nanoparticles in a large area, improving the resolution to 132 nm. This work suggests a new scope for the development of dynamic nonlinear fluorescent probes in super-resolution nanoscopy.