Noise characterization of an ultra-stable laser for optical clocks.

We report on the development and performance evaluation of an ultra-stable laser for an 27Al+ optical clock. After a series of noise suppressions, especially the vibrational and temperature fluctuation noise, the 30 cm long cavity stabilized laser obtains a frequency instability of 1.3 × 10-16 @1 s. This result is predicted by noise summation and confirmed by the three-cornered hat method. The 27Al+ optical clock transition is also used to characterize the laser frequency noise, and consistent results are yielded. This is the first reported instance of using single ion optical clocks to measure the frequency noise of ultra-stable lasers, as far as we know. With the implementation of the ultra-stable clock laser, an ultra-narrow linewidth clock transition of 2.8 Hz is obtained.

Robust Optical Physical Unclonable Function Based on Total Internal Reflection for Portable Authentication.

Physical unclonable functions (PUFs) utilize uncontrollable manufacturing randomness to yield cryptographic primitives. Currently, the fabrication of the most generally employed optical PUFs mainly depends on fluorescent, Raman, or plasmonic materials, which suffer inherent robustness issues. Herein, we construct an optical PUF with high environmental stability via total internal reflection (TIR-PUF) perturbed by randomly distributed polymer microspheres. The response image is transformed into encoded keys via an iterative binning procedure. The concentration of the polymer solution is optimized to debias the bit nonuniformity and maximize encoding capacity. The constructed TIR-PUF shows significantly high encoding capacity (2370) and markedly low total authentication error probability (1.614 × 10-23). The intra-Hamming distance is as low as 0.068, indicating the excellent readout reliability of TIR-PUF. The environmental stability of TIR-PUF has demonstrated promising results under a range of challenging conditions such as ultrasonic washing, high temperature, ultraviolet irradiation, and severe chemical environments. Moreover, the challenge-response pairs of our TIR-PUFs are demonstrated on an authentication system with low-power dissipation, lightweight components, and wireless imaging capture, rendering the possibility of portable authentication for practical applications.

Targeting programmed cell death in inflammatory bowel disease through natural products: New insights from molecular mechanisms to targeted therapies.

Inflammatory bowel disease (IBD) is an autoimmune disorder primarily characterized by intestinal inflammation and recurrent ulceration, leading to a compromised intestinal barrier and inflammatory infiltration. This disorder's pathogenesis is mainly attributed to extensive damage or death of intestinal epithelial cells, along with abnormal activation or impaired death regulation of immune cells and the release of various inflammatory factors, which contribute to the inflammatory environment in the intestines. Thus, maintaining intestinal homeostasis hinges on balancing the survival and functionality of various cell types. Programmed cell death (PCD) pathways, including apoptosis, pyroptosis, autophagy, ferroptosis, necroptosis, and neutrophil extracellular traps, are integral in the pathogenesis of IBD by mediating the death of intestinal epithelial and immune cells. Natural products derived from plants, fruits, and vegetables have shown potential in regulating PCD, offering preventive and therapeutic avenues for IBD. This article reviews the role of natural products in IBD treatment by focusing on targeting PCD pathways, opening new avenues for clinical IBD management.

Investigation on YSZ- and SiO2-Doped Mn-Fe Oxide Granules Based on Drop Technique for Thermochemical Energy Storage.

The Mn-Fe oxide material possesses the advantages of abundant availability, low cost, and non-toxicity as an energy storage material, particularly addressing the limitation of sluggish reoxidation kinetics observed in pure manganese oxide. However, scaling up the thermal energy storage (TCES) system poses challenges to the stability of the reactivities and mechanical strength of materials over long-term cycles, necessitating their resolution. In this study, Mn-Fe granules were fabricated with a diameter of approximately 2 mm using the feasible and scalable drop technique, and the effects of Y2O3-stabilized ZrO2 (YSZ) and SiO2 doping, at various doping ratios ranging from 1-20 wt%, were investigated on both the anti-sintering behavior and mechanical strength. In a thermal gravimetric analyzer, the redox reaction tests showed that both the dopants led to an enhancement in the reoxidation rates when the doping ratios were in an appropriate range, while they also brought about a decrease in the reduction rate and energy storage density. In a packed-bed reactor, the results of five consecutive redox tests showed a similar pattern to that in a thermal gravimetric analyzer. Additionally, the doping led to the stable reduction/oxidation reaction rates during the cyclic tests. In the subsequent 120 cyclic tests, the Si-doped granules exhibited volume expansion with a decreased crushing strength, whereas the YSZ-doped granules experienced drastic shrinkage with an increase in the crushing strength. The 1 wt% Si and 2 wt% Si presented the best synthetic performance, which resulted from the milder sintering effects during the long-term cyclic tests.

Human Placenta Decellularized Extracellular Matrix Hydrogel Promotes the Generation of Human Spinal Cord Organoids with Dorsoventral Organization from Human Induced Pluripotent Stem Cells.

Spinal cord organoids are of significant value in the research of spinal cord-related diseases by simulating disease states, thereby facilitating the development of novel therapies. However, the complexity of spinal cord structure and physiological functions, along with the lack of human-derived inducing components, presents challenges in the in vitro construction of human spinal cord organoids. Here, we introduce a novel human decellularized placenta-derived extracellular matrix hydrogel (DPECMH) and, combined with a new induction protocol, successfully construct human spinal cord organoids. The human placenta-sourced decellularized extracellular matrix (dECM), verified through hematoxylin and eosin staining, DNA quantification, and immunofluorescence staining, retained essential ECM components such as elastin, fibronectin, type I collagen, laminin, and so forth. The temperature-sensitive hydrogel made from human placenta dECM demonstrated good biocompatibility and promoted the differentiation of human induced pluripotent stem cell (hiPSCs)-derived spinal cord organoids into neurons. It displayed enhanced expression of laminar markers in comparison to Matrigel and showed higher expression of laminar markers compared to Matrigel, accelerating the maturation process of spinal cord organoids and demonstrating its potential as an organoid culture substrate. DPECMH has the potential to replace Matrigel as the standard additive for human spinal cord organoids, thus advancing the development of spinal cord organoid culture protocols and their application in the in vitro modeling of spinal cord-related diseases.

Seasonal hydrological dynamics affected the diversity and assembly process of the antibiotic resistome in a canal network.

The significant threat of antibiotic resistance genes (ARGs) to aquatic environments health has been widely acknowledged. To date, several studies have focused on the distribution and diversity of ARGs in a single river while their profiles in complex river networks are largely known. Here, the spatiotemporal dynamics of ARG profiles in a canal network were examined using high-throughput quantitative PCR, and the underlying assembly processes and its main environmental influencing factors were elucidated using multiple statistical analyses. The results demonstrated significant seasonal dynamics with greater richness and relative abundance of ARGs observed during the dry season compared to the wet season. ARG profiles exhibited a pronounced distance-decay pattern in the dry season, whereas no such pattern was evident in the wet season. Null model analysis indicated that deterministic processes, in contrast to stochastic processes, had a significant impact on shaping the ARG profiles. Furthermore, it was found that Firmicutes and pH emerged as the foremost factors influencing these profiles. This study enhanced our comprehension of the variations in ARG profiles within canal networks, which may contribute to the design of efficient management approaches aimed at restraining the propagation of ARGs.

Identification of a novel inflammatory-related gene signature to evaluate the prognosis of gastric cancer patients.

BACKGROUND: Gastric cancer (GC) is a highly aggressive malignancy with a heterogeneous nature, which makes prognosis prediction and treatment determination difficult. Inflammation is now recognized as one of the hallmarks of cancer and plays an important role in the aetiology and continued growth of tumours. Inflammation also affects the prognosis of GC patients. Recent reports suggest that a number of inflammatory-related biomarkers are useful for predicting tumour prognosis. However, the importance of inflammatory-related biomarkers in predicting the prognosis of GC patients is still unclear. AIM: To investigate inflammatory-related biomarkers in predicting the prognosis of GC patients. METHODS: In this study, the mRNA expression profiles and corresponding clinical information of GC patients were obtained from the Gene Expression Omnibus (GEO) database (GSE66229). An inflammatory-related gene prognostic signature model was constructed using the least absolute shrinkage and selection operator Cox regression model based on the GEO database. GC patients from the GSE26253 cohort were used for validation. Univariate and multivariate Cox analyses were used to determine the independent prognostic factors, and a prognostic nomogram was established. The calibration curve and the area under the curve based on receiver operating characteristic analysis were utilized to evaluate the predictive value of the nomogram. The decision curve analysis results were plotted to quantify and assess the clinical value of the nomogram. Gene set enrichment analysis was performed to explore the potential regulatory pathways involved. The relationship between tumour immune infiltration status and risk score was analysed via Tumour Immune Estimation Resource and CIBERSORT. Finally, we analysed the association between risk score and patient sensitivity to commonly used chemotherapy and targeted therapy agents. RESULTS: A prognostic model consisting of three inflammatory-related genes (MRPS17, GUF1, and PDK4) was constructed. Independent prognostic analysis revealed that the risk score was a separate prognostic factor in GC patients. According to the risk score, GC patients were stratified into high- and low-risk groups, and patients in the high-risk group had significantly worse prognoses according to age, sex, TNM stage and Lauren type. Consensus clustering identified three subtypes of inflammation that could predict GC prognosis more accurately than traditional grading and staging. Finally, the study revealed that patients in the low-risk group were more sensitive to certain drugs than were those in the high-risk group, indicating a link between inflammation-related genes and drug sensitivity. CONCLUSION: In conclusion, we established a novel three-gene prognostic signature that may be useful for predicting the prognosis and personalizing treatment decisions of GC patients.

Determinants of successful disease control through voluntary quarantine dynamics on social networks.

In the wake of epidemics, quarantine measures are typically recommended by health authorities or governments to help control the spread of the disease. Compared with mandatory quarantine, voluntary quarantine offers individuals the liberty to decide whether to isolate themselves in case of infection exposure, driven by their personal assessment of the trade-off between economic loss and health risks as well as their own sense of social responsibility and concern for public health. To better understand self-motivated health behavior choices under these factors, here we incorporate voluntary quarantine into an endemic disease model -- the susceptible-infected-susceptible (SIS) model -- and perform comprehensive agent-based simulations to characterize the resulting behavior-disease interactions in structured populations. We quantify the conditions under which voluntary quarantine will be an effective intervention measure to mitigate disease burden. Furthermore, we demonstrate how individual decision-making factors, including the level of temptation to refrain from quarantine and the degree of social compassion, impact compliance levels of voluntary quarantines and the consequent collective disease mitigation efforts. We find that successful disease control requires either a sufficiently low level of temptation or a sufficiently high degree of social compassion, such that even complete containment of the epidemic is attainable. In addition to well-mixed populations, our simulation results are applicable to other more realistic social networks of contacts, including spatial lattices, small-world networks, and real social networks. Our work offers new insights into the fundamental social dilemma aspect of disease control through non-pharmaceutical interventions, such as voluntary quarantine and isolation, where the collective outcome of individual decision-making is crucial.

High-power polarization-maintaining LP11-mode fiber laser based on long-period fiber grating for precise welding.

An LP11-mode output all-fiber laser was presented, utilizing long-period fiber gratings (LPFGs) and polarization-maintaining optical fiber (PMF). The LPFG was designed and fabricated, achieving a 90.56% efficiency in LP01 to LP11 mode conversion. Furthermore, the transmission stability of LP11-mode in the PMF was also explored, with the spatial mode overlap ratio exceeding 0.95. Ultimately, the high-power polarization-maintaining (PM) fiber laser, capable of the LP11 mode output, was constructed, with the output power of 600 W and the beam quality M2 of 2.84. During the process of welding a thick Al-plate, the LP11 fiber laser exhibits a notable 1.88 times greater depth of fusion compared to the commercial single-mode fiber laser, when operating at the laser welding head speed of 100 mm/s. For applications demanding non-circular symmetric high-order modes, this research holds substantial potential for widespread adoption within the field of industrial processing.

Physical Unclonable Functions Based on Photothermal Effect of Gold Nanoparticles.

Physical unclonable functions (PUFs) based on uncontrollable fabrication randomness are promising candidates for anticounterfeiting applications. Currently, the most popular optical PUFs are generally constructed from the scattering, fluorescent, or Raman phenomenon of nanomaterials. To further improve the security level of optical PUFs, advanced functions transparent to the above optical phenomenon have always been perused by researchers. Herein, we propose a new type of PUF based on the photothermal effect of gold nanoparticles, which shows negligible scattering, fluorescent, or Raman responses. The gold nanoparticles are randomly dispersed onto the surface of fused silica, which can enhance the photothermal effect and facilitate high contrast responses. By tuning the areal density of the gold nanoparticles, the optimized encoding capacity (2319) and the total authentication error probability (3.6428 × 10-24) are achieved from our PUF due to excellent bit uniformity (0.519) and inter Hamming distances (0.503). Moreover, the intra-Hamming distance (0.044) indicates the desired reliability. This advanced PUF with invisible features and high contrast responses provides a promising opportunity to implement authentication and identification with high security.

Climate warming promotes collateral antibiotic resistance development in cyanobacteria.

Both cyanobacterial blooms and antibiotic resistance have aggravated worldwide and posed a great threat to public health in recent years. As a significant source and reservoir of water environmental resistome, cyanobacteria exhibit confusing discrepancy between their reduced susceptibility and their chronic exposure to antibiotic mixtures at sub-inhibitory concentrations. How the increasing temperature affects the adaptive evolution of cyanobacteria-associated antibiotic resistance in response to low-level antibiotic combinations under climate change remains unclear. Here we profiled the antibiotic interaction and collateral susceptibility networks among 33 commonly detected antibiotics in 600 cyanobacterial strains isolated from 50 sites across four eutrophicated lakes in China. Cyanobacteria-associated antibiotic resistance level was found positively correlated to antibiotic heterogeneity across all sites. Among 528 antibiotic combinations, antagonism was observed for 62 % interactions and highly conserved within cyanobacterial species. Collateral resistance was detected in 78.5 % of pairwise antibiotic interaction, leading to a widened or shifted upwards mutant selection window for increased opportunity of acquiring second-step mutations. We quantified the interactive promoting effect of collateral resistance and increasing temperature on the evolution of both phenotypic and genotypic cyanobacteria-associated resistance under chronic exposure to environmental level of antibiotic combinations. With temperature increasing from 16 °C to 36 °C, the evolvability index and genotypic resistance level increased by 1.25 - 2.5 folds and 3 - 295 folds in the collateral-resistance-informed lineages, respectively. Emergence of resistance mutation pioneered by tolerance, which was jointly driven by mutation rate and persister fraction, was found to be accelerated by increased temperature and antibiotic switching rate. Our findings provided mechanic insights into the boosting effect of climate warming on the emergence and development of cyanobacteria-associated resistance against collateral antibiotic phenotypes.

Insight into the key factors and mechanism of excellent tetracycline adsorption on amorphous cobalt carbonate nanosheets.

The extensive use of tetracyclines (TCs) has led to their widespread distribution in the environment, causing serious harm to ecosystems because of their toxicity and resistance to decomposition. Adsorption is presently the principal approach to dispose of TCs, and the development of excellent adsorbents is crucial to TC removal. Herein, a novel amorphous cobalt carbonate hydroxide (ACCH) was successfully prepared by a one-step solvothermal method, which was identified as Co(CO3)0·63(OH)0.74·0.07H2O. The ultimate adsorption capacity of ACCH for TC reaches 2746 mg g-1, and the excellent adsorption performance can be maintained over a wide pH (3.0-11.0) and temperature (10-70 °C) range. Moreover, ACCH also exhibits a wonderful adsorption performance for other organic contaminants, such as ciprofloxacin and Rhodamine B. The TC adsorption process can be reasonably described by the pseudo-second-order kinetic model, intraparticle model and Langmuir isothermal model. The experimental results in this work suggest that the excellent adsorption performance of ACCH is ascribed to the large specific surface area, alkaline characteristics and numerous functional groups of ACCH. Accordingly, this work provides a promising strategy for the development of highly-efficient adsorbents and demonstrates their application prospects in environmental remediation.

Decellularized Brain Extracellular Matrix Hydrogel Aids the Formation of Human Spinal-Cord Organoids Recapitulating the Complex Three-Dimensional Organization.

The intricate electrophysiological functions and anatomical structures of spinal cord tissue render the establishment of in vitro models for spinal cord-related diseases highly challenging. Currently, both in vivo and in vitro models for spinal cord-related diseases are still underdeveloped, complicating the exploration and development of effective therapeutic drugs or strategies. Organoids cultured from human induced pluripotent stem cells (hiPSCs) hold promise as suitable in vitro models for spinal cord-related diseases. However, the cultivation of spinal cord organoids predominantly relies on Matrigel, a matrix derived from murine sarcoma tissue. Tissue-specific extracellular matrices are key drivers of complex organ development, thus underscoring the urgent need to research safer and more physiologically relevant organoid culture materials. Herein, we have prepared a rat decellularized brain extracellular matrix hydrogel (DBECMH), which supports the formation of hiPSC-derived spinal cord organoids. Compared with Matrigel, organoids cultured in DBECMH exhibited higher expression levels of markers from multiple compartments of the natural spinal cord, facilitating the development and maturation of spinal cord organoid tissues. Our study suggests that DBECMH holds potential to replace Matrigel as the standard culture medium for human spinal cord organoids, thereby advancing the development of spinal cord organoid culture protocols and their application in in vitro modeling of spinal cord-related diseases.

Optimizing dietary rumen-degradable starch to rumen-degradable protein ratio improves lactation performance and nitrogen utilization efficiency in mid-lactating Holstein dairy cows.

The dietary rumen-degradable starch (RDS) to rumen-degradable protein (RDP) ratio, denoted as the RDS-to-RDP ratio (SPR), has been proven to enhance in vitro rumen fermentation. However, the effects of dietary SPR in vivo remain largely unexplored. This study was conducted to investigate the effect of dietary SPR on lactation performance, nutrient digestibility, rumen fermentation patterns, blood indicators, and nitrogen (N) partitioning in mid-lactating Holstein cows. Seventy-two Holstein dairy cows were randomly assigned to three groups (24 head/group), balanced for (mean ± standard deviation) days in milk (116 ± 21.5), parity (2.1 ± 0.8), milk production (42 ± 2.1 kg/d), and body weight (705 ± 52.5 kg). The cows were fed diets with low (2.1, control), medium (2.3), or high (2.5) SPR, formulated to be isoenergetic, isonitrogenous, and iso-starch. The study consisted of a one-week adaptation phase followed by an eight-week experimental period. The results indicated that the high SPR group had a lower dry matter intake compared to the other groups (p < 0.05). A quadratic increase in milk yield and feed efficiency was observed with increasing dietary SPR (p < 0.05), peaking in the medium SPR group. The medium SPR group exhibited a lower milk somatic cell count and a higher blood total antioxidant capacity compared to other groups (p < 0.05). With increasing dietary SPR, there was a quadratic improvement (p < 0.05) in the total tract apparent digestibility of crude protein, ether extract, starch, neutral detergent fiber, and acid detergent fiber. Although no treatment effect was observed in rumen pH, the rumen total volatile fatty acids concentration and microbial crude protein synthesis increased quadratically (p < 0.05) as dietary SPR increased. The molar proportion of propionate linearly increased (p = 0.01), while branched-chain volatile fatty acids linearly decreased (p = 0.01) with increasing dietary SPR. The low SPR group (control) exhibited higher concentration of milk urea N, rumen ammonia N, and blood urea N than other groups (p < 0.05). Despite a linear decrease (p < 0.05) in the proportion of urinary N to N intake, increasing dietary SPR led to a quadratic increase (p = 0.01) in N utilization efficiency and a quadratic decrease (p < 0.05) in the proportion of fecal N to N intake. In conclusion, optimizing dietary SPR has the potential to enhance lactation performance and N utilization efficiency. Based on our findings, a medium dietary SPR (with SPR = 2.3) is recommended for mid-lactating Holstein dairy cows. Nevertheless, further research on rumen microbial composition and metabolites is warranted to elucidate the underlying mechanisms of the observed effects.

[Optimization of production-living-ecology spatial pattern in Dongting Lake Ecological Economic Zone based on comprehensive benefits of development and protection]. / 基于开发保护综合效益的洞庭湖生态经济区"三生空间"æ ¼å±€ä¼˜åŒ–.

The optimization of production-living-ecology (PLE) space is an important basis for promoting regional high-quality development. Taking the Dongting Lake Eco-economic Zone as an example, from the perspective of improving the comprehensive benefits of the development and protection of the PLE space, we coupled the GMOP-FLUS model, and proposed an optimization method combining the scenario configuration and the bottom line protection of the PLE space. We compared the three optimization scenarios (economic optimization scenario, ecological optimization scenario, and multi-objective optimization scenario), and coordinated the conflict areas of two lines to clarify the comprehensive optimization scheme of the PLE space in the Dongting Lake Eco-economic Zone. The results showed the characteristics of increasing production space and living space and decreasing ecological space from 2010 to 2020, resulting in the partial loss of land ecological and environmental benefits. Under the economic optimization scenario, the ecological optimization scenario promoted the rapid growth of regional economy but damaged regional ecological security. The ecological optimization scenario inhibited regional economic development. The multi-objective optimization scenario led to improvement of economic and ecological benefits of the PLE space, which increased by 2.0% and 1.3%, respectively. The multi-objective optimization scenario was the best optimization scenario among the three scenarios. By superimposing the best scenario and the two-line conflict regional coordination results, we obtained the comprehensive optimization scheme for 2030. The production space, living space, and ecological space areas of the scheme were 25777.18, 2062.94, and 32552.68 km2, respectively. Based on the natural and social conditions, combining the comprehensive optimization scheme, we put forward different control suggestions for each type of PLE space. Our results could provide reference for the rational formulation of territorial spatial planning and the formulation of policies for the coordinated development of ecological environment and social economy in the Dongting Lake Eco-economic Zone.

Value of early pregnancy ultrasound combined with ultrasound score in the evaluation of placenta accreta in scar uterus: A retrospective cohort study.

The objective of this study is to investigate the value of early pregnancy ultrasound combined with ultrasound score (USS) for the evaluation of placenta accreta (PA) in scar uteri. Thirty cases of PA in scar uteri diagnosed by ultrasound at our hospital between June 2021 and June 2022 were selected retrospectively (observation group). In addition, 30 patients had placenta attached to the anterior wall of the uterus and covered the internal orifice of the cervix; however, no PA was selected in the same period (control group). The results of surgical pathology and ultrasound examination in the first trimester of pregnancy (11-14 weeks of pregnancy, fetal top hip length 4.5-8.4 cm) were analyzed. Ultrasonic image characteristics of the 2 groups were scored using an ultrasonic scoring scale. The ultrasonic signs and ultrasonic scores of the 2 groups were analyzed. The diagnostic value of ultrasound and USS for PA in the scarred uterus alone and in combination was analyzed based on the gold standard of surgical and pathological results. The rich blood flow signal at the junction of the uterine serosa and bladder, the rate of blood flow in the cavity of the placental parenchyma, the thinning rate of the myometrium after placenta, and the abnormal rate of the low echo area after placenta in the observation group were significantly higher than those in the control group (P < .05). The USS of the observation group was significantly higher than that of the control group (P < .05). The sensitivity (93.33%) and accuracy (95.00%) of the combined examinations were significantly higher than those of ultrasound (70.00% and 83.33%, respectively) (P < .05). The sensitivity and accuracy of combined examination were slightly higher than those of USS examination (83.33% and 90.00%), but the difference was not statistically significant (P > .05). There was no significant difference between the specificity of combined examination (93.33%) and ultrasound (96.67%) and USS (96.67%) (P > .05). Early pregnancy ultrasound and USS evaluation have high application value in the diagnosis and evaluation of early scar uterine PA. The combination of the 2 methods can further improve the sensitivity and accuracy of diagnosis.

Measuring and classifying IP usage scenarios: a continuous neural trees approach.

Understanding user behavior via IP addresses is a crucial measure towards numerous pragmatic IP-based applications, including online content delivery, fraud prevention, marketing intelligence, and others. While profiling IP addresses through methods like IP geolocation and anomaly detection has been thoroughly studied, the function of an IP address-e.g., whether it pertains to a private enterprise network or a home broadband-remains underexplored. In this work, we initiate the first attempt to address the IP usage scenario classification problem. We collect data consisting of IP addresses from four large-scale regions. A novel continuous neural tree-based ensemble model is proposed to learn IP assignment rules and complex feature interactions. We conduct extensive experiments to evaluate our model in terms of classification accuracy and generalizability. Our results demonstrate that the proposed model is capable of efficiently uncovering significant higher-order feature interactions that enhance IP usage scenario classification, while also possessing the ability to generalize from the source region to the target one.

Identification of molecular subtypes and a prognostic signature based on m6A/m5C/m1A-related genes in lung adenocarcinoma.

Lung cancer, specifically the histological subtype lung adenocarcinoma (LUAD), has the highest global occurrence and fatality rate. Extensive research has indicated that RNA alterations encompassing m6A, m5C, and m1A contribute actively to tumorigenesis, drug resistance, and immunotherapy responses in LUAD. Nevertheless, the absence of a dependable predictive model based on m6A/m5C/m1A-associated genes hinders accurately predicting the prognosis of patients diagnosed with LUAD. In this study, we collected patient data from The Cancer Genome Atlas (TCGA) and identified genes related to m6A/m5C/m1A modifications using the GeneCards database. The "ConsensusClusterPlus" R package was used to produce molecular subtypes by utilizing genes relevant to m6A/m5C/m1A identified through differential expression and univariate Cox analyses. An independent prognostic factor was identified by constructing a prognostic signature comprising six genes (SNHG12, PABPC1, IGF2BP1, FOXM1, CBFA2T3, and CASC8). Poor overall survival and elevated expression of human leukocyte antigens and immune checkpoints were correlated with higher risk scores. We examined the associations between the sets of genes regulated by m6A/m5C/m1A and the risk model, as well as the immune cell infiltration, using algorithms such as ESTIMATE, CIBERSORT, TIMER, ssGSEA, and exclusion (TIDE). Moreover, we compared tumor stemness indices (TSIs) by considering the molecular subtypes related to m6A/m5C/m1A and risk signatures. Analyses were performed based on the risk signature, including stratification, somatic mutation analysis, nomogram construction, chemotherapeutic response prediction, and small-molecule drug prediction. In summary, we developed a prognostic signature consisting of six genes that have the potential for prognostication in patients with LUAD and the design of personalized treatments that could provide new versions of personalized management for these patients.

Theabrownins in dark tea form complexes with tea polysaccharide conjugates.

BACKGROUND: Theabrownins (TBs) are one of most important quality components in dark tea, but have not been produced industrially. In this study, the aqueous extract was obtained from Pu-erh ripe tea, one kind of dark tea. Caffeine, theaflavin, catechin and saponin were removed by trichloromethane, ethyl acetate and n-butanol in turn to obtain a TB isolate. The TB isolate was subjected to column chromatography using a macroporous resin HPD-750 and eluted with a gradient of 0-700 g kg-1 ethanol aqueous solution. Four fractions were obtained, and named as TBs-FC1, TBs-FC2, TBs-FC3 and TBs-FC4. RESULTS: These four fractions contained polysaccharides and no small molecules such as catechins, caffeine and theaflavins as well as average molecular weights of 123.000 kDa, 23.380 kDa, 89.870 kDa and 106.600 kDa. It was revealed that they were complexes of TBs and tea polysaccharide conjugates (TPCs). Ultraviolet-visible (UV-visible) and infrared (IR) spectra showed the properties of TBs and TPCs. Their zeta potentials ranged from -13.40 mV to -38.80 mV in aqueous solutions at pH 3.0-9.0. CONCLUSION: This study reveals that TBs do not exist in free state but in combined state in dark tea, which provide the theoretical basis for the industrialization of TBs. © 2024 Society of Chemical Industry.

Case report: Tall cell carcinoma with reversed polarity of the breast: an additional case and review of the literature.

Objective: The aim of this report was to comprehensively investigate the clinicopathological features, histological characteristics, and differential diagnosis of tall cell carcinoma with reversed polarity of the breast (TCCRP) to enhance the understanding of this tumour for precise therapeutic interventions. Methods: The clinicopathological characteristics and differential diagnosis of a patient with TCCRP were retrospectively analysed, and a systematic literature review was extracted from relevant published studies on PubMed. Results: All patients included in the study were female, with a median age of 51 years. Microscopically, the tumour cells exhibited a solid papillary growth pattern with tall columnar morphology and reversed nuclear polarity. Immunohistochemistry revealed that the tumours were triple-negative breast cancer (negative for ER, PR, and HER-2), with a low Ki-67 proliferation index. Different degrees of expression were observed for CK7, Calretinin, and S-100 markers; however, CK5/6 showed high expression levels. Conclusions: TCCRP is an uncommon invasive carcinoma subtype found in the breast. Its histological morphology resembles that of tall cell subtype papillary thyroid carcinoma. Accurate diagnosis requires the integration of histomorphological assessment along with immunohistochemistry and molecular genetics analysis.