Enhanced Circular Dichroism for Achiral Sensing Based on a DNA-Origami-Empowered Anapole Metasurface.

Circular dichroism (CD) spectroscopy has been extensively utilized for detecting and distinguishing the chirality of diverse substances and structures. However, CD spectroscopy is inherently weak and conventionally associated with chiral sensing, thus constraining its range of applications. Here, we report a DNA-origami-empowered metasurface sensing platform through the collaborative effect of metasurfaces and DNA origami, enabling achiral/slightly chiral sensing with high sensitivity via the enhanced ΔCD. An anapole metasurface, boasting over 60 times the average optical chirality enhancement, was elaborately designed to synergize with reconfigurable DNA origami. We experimentally demonstrated the detection of achiral/slightly chiral DNA linker strands via the enhanced ΔCD of the proposed platform, whose sensitivity was a 10-fold enhancement compared with the platform without metasurfaces. Our work presents a high-sensitivity platform for achiral/slightly chiral sensing through chiral spectroscopy, expanding the capabilities of chiral spectroscopy and inspiring the integration of multifunctional artificial nanostructures across diverse domains.

Management of patient with Fusobacterim nucletum related pleural empyema: intrapleural antibiotic therapy can be considered for salvage therapy.

Pleural empyema can lead to significant morbidity and mortality despite chest drainage and antibiotic treatment, necessitating novel and minimally invasive interventions. Fusobacterium nucleatum is an obligate anaerobe found in the human oral and gut microbiota. Advances in sequencing and puncture techniques have made it common to detect anaerobic bacteria in empyema cases. In this report, we describe the case of a 65-year-old man with hypertension who presented with a left-sided encapsulated pleural effusion. Initial fluid analysis using metagenomic next-generation sequencing (mNGS) revealed the presence of Fusobacterium nucleatum and Aspergillus chevalieri. Unfortunately, the patient experienced worsening pleural effusion despite drainage and antimicrobial therapy. Ultimately, successful treatment was achieved through intrapleural metronidazole therapy in conjunction with systemic antibiotics. The present case showed that intrapleural antibiotic therapy is a promising measure for pleural empyema.

The role of CD8+ T-cells in colorectal cancer immunotherapy.

Immunotherapy has been an advanced and effective approach to treating various types of solid tumors in recent years, and the most successful strategy is immune checkpoint inhibitors (ICIs), which have shown beneficial effects in patients with colorectal cancer (CRC). Drug resistance to ICIs is usually associated with CD8+ T-cells targeting tumor antigens; thus, CD8+ T-cells play an important role in immunotherapy. Unfortunately, Under continuous antigen stimulation, tumor microenvironment(TME), hypoxia and other problems it leads to insufficient infiltration of CD8+ T-cells, low efficacy and mechanism exhaustion, which have become obstacles to immunotherapy. Thus, this article describes the relationship between CRC and the immune system, focuses on the process of CD8+ T-cells production, activation, transport, killing, and exhaustion, and expounds on related mechanisms leading to CD8+ T-cells exhaustion. Finally, this article summarizes the latest strategies and methods in recent years, focusing on improving the infiltration, efficacy, and exhaustion of CD8+ T-cells, which may help to overcome the barriers to immunotherapy.

Defect Engineering in Ce-Based Metal-Organic Frameworks toward Enhanced Catalytic Performance for Hydrogenation of Dicyclopentadiene.

Defective metal-organic frameworks (MOFs) have shown great potential for catalysis due to abundant active sites and adjustable physical and chemical properties. A series of Ce-based MOFs with different defect contents were synthesized via a modulator-induced defect engineering strategy with the aid of the cell pulverization technique. The effects of modulators on the pore structure, morphology, valence distribution of Ce, and Lewis acidity of Ce-MOF-801 were systematically investigated. Among the different samples studied, the optimal Ce-MOF-801-50eq sample exhibited remarkable catalytic activity for DCPD hydrogenation, achieving a conversion rate of 100%, which is significantly higher compared to other Ce-MOF-801-neq samples as well as the Zr-MOF-801-50eq and Hf-MOF-801-50eq samples. The enhanced catalytic performance of Ce-MOF-801-50eq can be attributed to advantages provided by defect engineering, such as the high specific surface area, proper pore size distribution, abundant unsaturated metal sites, and Ce3+/Ce4+ atom ratio, which have been supported by various characterizations. This study provides important insights into the rational design of Ce-MOFs in the field of catalytic DCPD hydrogenation.

Analysis of delayed initial radioactive iodine therapy and clinical outcomes in papillary thyroid cancer: a two-center retrospective study.

BACKGROUND: It remains unclear whether the time interval between total thyroidectomy and radioactive iodine (RAI) therapy influences clinical outcomes in papillary thyroid carcinoma (PTC). This study aims to evaluate the impact of the timing to initiate RAI therapy on the response in PTC patients. METHODS: We retrospectively included 405 patients who underwent total thyroidectomy and subsequent RAI therapy at two tertiary hospitals in southwest China. Patients were categorized into two groups based on the interval between thyroidectomy and initial RAI therapy, that is, an early group (interval ≤90 days, n = 317) and a delayed group (interval >90 days, n = 88). Responses to RAI therapy were classified as excellent, indeterminate, biochemical incomplete, or structural incomplete. Univariate and multivariate analyses were conducted to identify factors associated with a nonexcellent response. RESULTS: Excellent responses were observed in 77.3% of the early group and 83.0% of the delayed group (P = 0.252). No significant impact of RAI therapy timing was also observed across all American Thyroid Association risk classification categories. These findings persisted when patients were analyzed separately according to RAI dose (intermediate-dose group: 3.7 GBq [n = 332]; high-activity group: ≥5.5 GBq [n = 73]), further subdivided by the timing of RAI therapy. Multivariate analysis identified lymph node dissection, RAI dose, and stimulated thyroglobulin as independent risk factors for excellent response (P < 0.05). CONCLUSION: The timing of initial RAI therapy following surgery did not significantly affect outcomes in patients with PTC.

Reversible Phase Transformations in a Double-Walled Diamondoid Coordination Network with a Stepped Isotherm for Methane.

Flexible metal-organic materials (FMOMs) with stepped isotherms can offer enhanced working capacity in storage applications such as adsorbed natural gas (ANG) storage. Unfortunately, whereas >1000 FMOMs are known, only a handful exhibit methane uptake of >150 cm3/cm3 at 65 atm and 298 K, conditions relevant to ANG. Here, we report a double-walled 2-fold interpenetrated diamondoid (dia) network, X-dia-6-Ni, [Ni2L4(µ-H2O)]n, comprising a new azo linker ligand, L- (L- = (E)-3-(pyridin-4-yldiazenyl)benzoate) and 8-connected dinuclear molecular building blocks. X-dia-6-Ni exhibited gas (CO2, N2, CH4) and liquid (C8 hydrocarbons)-induced reversible transformations between its activated narrow-pore ß phase and γ, a large-pore phase with ca. 33% increase in unit cell volume. Single-crystal X-ray diffraction (SCXRD) studies of the as-synthesized phase α, ß, and γ revealed that structural transformations were enabled by twisting of the azo moiety and/or deformation of the MBB. Further insight into these transformations was gained from variable temperature powder XRD and in situ variable pressure powder XRD. Low-temperature N2 and CO2 sorption revealed stepped Type F-II isotherms with saturation uptakes of 422 and 401 cm3/g, respectively. X-dia-6-Ni exhibited uptake of 200 cm3/cm3 (65 atm, 298 K) and a high CH4 working capacity of 166 cm3/cm3 (5-65 bar, 298 K, 33 cycles), the third highest value yet reported for an FMOM and the highest value for an FMOM with a Type F-II isotherm.

Propulsion mechanisms of micro/nanorobots: a review.

Micro/nanomotors (MNMs) are intelligent, efficient and promising micro/nanorobots (MNR) that can respond to external stimuli (e.g., chemical energy, temperature, light, pH, ultrasound, magnetic, biosignals, ions) and perform specific tasks. The MNR can adapt to different external stimuli and transform into various functional forms to match different application scenarios. So far, MNR have found extensive application in targeted therapy, drug delivery, tissue engineering, environmental remediation, and other fields. Despite the promise of MNR, there are few reviews that focus on them. To shed new light on the further development of the field, it is necessary to provide an overview of the current state of development of these MNR. Therefore, this paper reviews the research progress of MNR in terms of propulsion mechanisms, and points out the pros and cons of different stimulus types. Finally, this paper highlights the current challenges faced by MNR and proposes possible solutions to facilitate the practical application of MNR.

Response of chlorophyll-a to rainfall event in the basin of the South China sea: Statistical analysis.

Chlorophyll-a (Chl-a) is an essential ecological indicator, and affected by processes such as typhoons, mesoscale eddies, and Rossby waves. However, the impact of more frequent and widespread precipitation events on Chl-a seems to be overlooked. This study utilized remote sensing data and reanalysis data to investigate the response of Chl-a to 240 precipitation events in the central South China Sea from 2005 to 2019. The results indicate that precipitation events have a significant impact on Chl-a concentration. Following a precipitation event in 2019, the Chl-a concentration in the affected area increased by approximately 0.22 mg m-³ from the 3rd to the 7th day. The reasons for the increase in Chl-a concentration were the vertical mixing induced by wind stirring and the upwelling caused by wind stress curl, which transported nutrients to the euphotic zone, lowering the sea surface temperature and triggering a proliferation of phytoplankton. Additionally, dissolved nutrients in precipitation provided a nutrient source for Chl-a growth. The contributions of nutrient supply, wind speed, and wind stress curl to the increase in Chl-a concentration during precipitation events were 18%, 37%, and 45%, respectively. Precipitation events enhanced marine primary productivity, playing a crucial role in deepening our understanding of ocean-atmosphere interactions and their impact on marine ecosystem.

Genomic characterization and risk stratification of esophageal squamous dysplasia.

Objectives: The majority of esophageal squamous dysplasia (ESD) patients progress slowly, while a subset of patients can undergo recurrence rapidly or progress to invasive cancer even after proper treatment. However, the molecular mechanisms underlying these clinical observations are still largely unknown. Methods: By sequencing the genomic data of 160 clinical samples from 49 tumor-free ESD patients and 88 esophageal squamous cell carcinoma (ESCC) patients, we demonstrated lower somatic mutation and copy number alteration (CNA) burden in ESD compared with ESCC. Results: Cross-species screening and functional assays identified ACSM5 as a novel driver gene for ESD progression. Furthermore, we revealed that miR-4292 promoted ESD progression and could serve as a non-invasive diagnostic marker for ESD. Conclusions: These findings largely expanded our understanding of ESD genetics and tumorigenesis, which possessed promising significance for improving early diagnosis, reducing overtreatment, and identifying high-risk ESD patients.

Preparation of NIR-II Polymer Nanoprobe Through Twisted Intramolecular Charge Transfer and Förster Resonance Energy Transfer of NIR-I Dye.

Near-infrared-II (NIR-II) fluorescence imaging is pivotal in biomedical research. Organic probes exhibit high potential in clinical translation, due to advantages such as precise structure design, low toxicity, and post-modifications convenience. In related preparation, enhancement of NIR-II tail emission from NIR-I dyes is an efficient method. In particular, the promotion of twisted intramolecular charge transfer (TICT) of relevant NIR-I dyes is a convenient protocol. However, present TICT-type probes still show disadvantages in relatively low emission, large particle sizes, or limited choice of NIR-I dyes, etc. Herein, the synthesis of stable small-sized polymer NIR-II fluoroprobes (e.g., 7.2 nm), integrating TICT and Förster resonance energy transfer process to synergistically enhance the NIR-II emission is reported. Strong enhanced emissions can be obtained from various NIR-I dyes and lanthanide elements (e.g., twelvefold at 1250 nm from Nd-DTPA/IR-808 sample). The fluorophore provides high-resolution angiography, with high-contrast imaging on middle cerebral artery occlusion model mice for distinguishing occlusion. The fluorophore can be rapidly excreted from the kidney (urine ≈65% within 4 h) in normal mice and exhibits long-term renal retention on acute kidney injury mice, showing potential applications in the prognosis of kidney diseases. This development provides an effective strategy to design and synthesize effective NIR-II fluoroprobes.

Study on Anomalous Hall Effect and Spin-Orbit Torque Effect of TbCo-Based Multilayer Films.

The anomalous Hall effect and spin-orbit torque of TbCo-based multilayer films have been methodically studied in recent years. Many properties of the films can be obtained by the anomalous Hall resistance loops of the samples. We report on the effects of a structure composed of two heavy metals as the buffer layers on the anomalous Hall resistance loops of TbCo-based multilayers at different temperatures. The results showed that the coercivity increases dramatically with decreasing temperature, and the samples without perpendicular magnetic anisotropy at room temperature showed perpendicular magnetic anisotropy at low temperatures. We quantified the spin-orbit torque efficiency and Dzyaloshinskii-Moriya interaction effective field size of the films W/Pt/TbCo/Pt at room temperature by measuring the loop shift of anomalous Hall resistance. The results showed that the study of anomalous Hall resistance loops plays an important role in the study of spintronics, which can not only show the basic properties of the sample, but can also obtain other information about the sample through the shift of the loops.

UCHL5 promotes hepatocellular carcinoma progression by promoting glycolysis through activating Wnt/ß-catenin pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is highly malignant with a dismal prognosis, although the available therapies are insufficient. No efficient ubiquitinase has been identified as a therapeutic target for HCC despite the complicating role that of proteins ubiquitination plays in the malignant development of HCC. METHODS: The expression of ubiquitin carboxyl terminal hydrolase L5 (UCHL5) in HCC tumor tissue and adjacent normal tissue was determined using the cancer genome atlas (TCGA) database and was validated using real-time quantitative polymerase chain reaction (RT-qRCR), Western blot and immunohistochemistry (IHC), and the relation of UCHL5 with patient clinical prognosis was explored. The expression of UCHL5 was knocked down and validated, and the effect of UCHL5 on the biological course of HCC was explored using cellular assays. To clarify the molecular mechanism of action of UCHL5 affecting HCC, expression studies of Adenosine triphosphate adenosine triphosphate (ATP), extracellular acidification (ECAR), and glycolysis-related enzymes were performed. The effects of UCHL5 on ß-catenin ubiquitination and Wnt signaling pathways were explored in depth and validated using cellular functionalities. Validation was also performed in vivo. RESULTS: In the course of this investigation, we discovered that UCHL5 was strongly expressed in HCC at both cellular and tissue levels. The prognosis of patients with high UCHL5 expression is considerably worse than that of those with low UCHL5 expression. UCHL5 has been shown to increase the degree of glycolysis in HCC cells with the impact of stimulating the proliferation and metastasis of HCC cells in both in vivo and in vitro. UCHL5 downregulates its degree of ubiquitination by binding to ß-catenin, which activates the Wnt/ß-catenin pathway and accelerates HCC cell glycolysis. Thereby promoting the growth of the HCC. CONCLUSIONS: In summary, we have demonstrated for the first time that UCHL5 is a target of HCC and promotes the progression of hepatocellular carcinoma by promoting glycolysis through the activation of the Wnt/ß-catenin pathway. UCHL5 may thus serve as a novel prognostic marker and therapeutic target for the treatment of HCC.

Mercury contamination is an invisible threat to declining migratory shorebirds along the East Asian-Australasian Flyway.

Exposure to pollutants is a potentially crucial but overlooked driver of population declines in shorebirds along the East Asian-Australasian Flyway. We combined knowledge of moult strategy and life history with a standardised sampling protocol to assess mercury (Hg) contamination in 984 individuals across 33 migratory shorebird species on an intercontinental scale. Over one-third of the samples exceeded toxicity benchmarks. Feather Hg was best explained by moulting region, while habitat preference (coastal obligate vs. non-coastal obligate), the proportion of invertebrates in the diet and foraging stratum (foraging mostly on the surface vs. at depth) also contributed, but were less pronounced. Feather Hg was substantially higher in South China (Mai Po and Leizhou), Australia and the Yellow Sea than in temperate and Arctic breeding ranges. Non-coastal obligate species (Tringa genus) frequently encountered in freshwater habitats were at the highest risk. It is important to continue and expand biomonitoring research to assess how other pollutants might impact shorebirds.

Breaking the Tumor Chronic Inflammation Balance with a Programmable Release and Multi-Stimulation Engineering Scaffold for Potent Immunotherapy.

Tumor-associated chronic inflammation severely restricts the efficacy of immunotherapy in cold tumors. Here, a programmable release hydrogel-based engineering scaffold with multi-stimulation and reactive oxygen species (ROS)-response (PHOENIX) is demonstrated to break the chronic inflammatory balance in cold tumors to induce potent immunity. PHOENIX can undergo programmable release of resiquimod and anti-OX40 under ROS. Resiquimod is first released, leading to antigen-presenting cell maturation and the transformation of myeloid-derived suppressor cells and M2 macrophages into an antitumor immune phenotype. Subsequently, anti-OX40 is transported into the tumor microenvironment, leading to effector T-cell activation and inhibition of Treg function. PHOENIX consequently breaks the chronic inflammation in the tumor microenvironment and leads to a potent immune response. In mice bearing subcutaneous triple-negative breast cancer and metastasis models, PHOENIX effectively inhibited 80% and 60% of tumor growth, respectively. Moreover, PHOENIX protected 100% of the mice against TNBC tumor rechallenge by electing a robust long-term antigen-specific immune response. An excellent inhibition and prolonged survival in PHOENIX-treated mice with colorectal cancer and melanoma is also observed. This work presents a potent therapeutic scaffold to improve immunotherapy efficiency, representing a generalizable and facile regimen for cold tumors.

Epigenetic silencing schlafen-11 sensitizes esophageal cancer to ATM inhibitor.

BACKGROUND: Targeting DNA damage response (DDR) pathway is a cutting-edge strategy. It has been reported that Schlafen-11 (SLFN11) contributes to increase chemosensitivity by participating in DDR. However, the detailed mechanism is unclear. AIM: To investigate the role of SLFN11 in DDR and the application of synthetic lethal in esophageal cancer with SLFN11 defects. METHODS: To reach the purpose, eight esophageal squamous carcinoma cell lines, 142 esophageal dysplasia (ED) and 1007 primary esophageal squamous cell carcinoma (ESCC) samples and various techniques were utilized, including methylation-specific polymerase chain reaction, CRISPR/Cas9 technique, Western blot, colony formation assay, and xenograft mouse model. RESULTS: Methylation of SLFN11 was exhibited in 9.15% of (13/142) ED and 25.62% of primary (258/1007) ESCC cases, and its expression was regulated by promoter region methylation. SLFN11 methylation was significantly associated with tumor differentiation and tumor size (both P < 0.05). However, no significant associations were observed between promoter region methylation and age, gender, smoking, alcohol consumption, TNM stage, or lymph node metastasis. Utilizing DNA damaged model induced by low dose cisplatin, SLFN11 was found to activate non-homologous end-joining and ATR/CHK1 signaling pathways, while inhibiting the ATM/CHK2 signaling pathway. Epigenetic silencing of SLFN11 was found to sensitize the ESCC cells to ATM inhibitor (AZD0156), both in vitro and in vivo. CONCLUSION: SLFN11 is frequently methylated in human ESCC. Methylation of SLFN11 is sensitive marker of ATM inhibitor in ESCC.

Type II Crigler-Najjar syndrome: a case report and literature review.

Background: Crigler-Najjar syndrome (CNS) is caused by mutations in uridine 5'-diphosphate glucuronyltransferase (UGT1A1) resulting in enzyme deficiency and hyperbilirubinemia. Type II CNS patients could respond to phenobarbital treatment and survive. This study presents a rare case of type II CNS. Case summary: The proband was a 29-year-old male patient admitted with severe jaundice. A hepatic biopsy showed bullous steatosis of the peri-central veins of the hepatic lobule, sediment of bile pigment, and mild periportal inflammation with normal liver plate structure. The type II CNS was diagnosed by routine genomic sequencing which found that the proband with the Gry71Arg/Tyr486Asp compound heterozygous mutations in the UGT1A1 gene. After treatment with phenobarbital (180 mg/day), his bilirubin levels fluctuated between 100 and 200 µmol/L for 6 months and without severe icterus. Conclusion: Type II CNS could be diagnosed by routine gene sequencing and treated by phenobarbital.

Neurobrucellosis: laboratory features, clinical characteristics, antibiotic treatment, and clinical outcomes of 21 patients.

BACKGROUND: Neurobrucellosis (NB) is a rare and serious complication of brucellosis. Its clinical manifestations vary, with no obvious specificity. At present, there is no clear clinical diagnosis or treatment for reference. In this study, we retrospectively analyzed the clinical data for 21 patients with NB to provide reference data for its further study. METHODS: We analyzed the epidemiological and clinical manifestations, laboratory tests, imaging examinations, cerebrospinal fluid, and treatment plans of 21 patients diagnosed with NB in the Department of Neurology, Xuanwu Hospital, Capital Medical University Beijing, China. RESULTS: The ages of the patients ranged from 15 to 60 years old (mean age 40.1 ± 13.33 years), the male: female ratio was 4.25:1. Thirteen patients had a history of animal (sheep, cattle) contact, three had no history of animal contact, and the contact status of four was unknown. Brucella can invade various systems of the body and show multi-system symptoms, the main general manifestations were fever (66.67%), fatigue (57.14%) and functional urination or defecation disturbance (42.86%). The main nervous system manifestations were limb weakness (52.38%) and hearing loss (47.62%).The main positive signs of the nervous system included positive pathological signs (71.43%), sensory abnormalities (52.38%), limb paralysis (42.86%). Nervous system lesions mainly included spinal cord damage (66.67%), cranial nerve involvement (61.90%), central demyelination (28.57%) and meningitis (28.57%). In patients with cranial nerve involvement, 69.23% of auditory nerve, 15.38% of optic nerve and 15.38% of oculomotor nerve were involved. The blood of eight patients was cultured for Brucella, and three (37.5%) cultures were positive and five (63.5%) negative. The cerebrospinal fluid (CSF) of eight patients was cultured for Brucella, and two (25.00%) cultures were positive and six (75.00%) negative. Nineteen of the patients underwent a serum agglutination test (SAT), 18 (94.74%) of whom were positive and one (5.26%) of whom were negative. A biochemical analysis of the CSF was performed in 21 patients, and the results were all abnormal. Nineteen patients underwent magnetic resonance imaging (MRI). Twenty-one patients were treated with doxycycline and/or rifampicin, combined with ceftriaxone, quinolone, aminoglycoside, or minocycline. After hospitalization, 15 patients improved (71.43%), two patients did not recover, and the status of four patients was unknown. CONCLUSIONS: The clinical manifestations, CSF parameters, and neurological imaging data for patients with NB show no significant specificity or correlations. When patients with unexplained neurological symptoms accompanied by fever, fatigue, and other systemic manifestations in a brucellosis epidemic area or with a history of contact with cattle, sheep, animals, or raw food are encountered in clinical practice, the possibility of NB should be considered. Treatment is based on the principles of an early, combined, and long course of treatment, and the general prognosis is good.

Lithium-Ion-Doped Eutectogel for Surface-Capacitive Sensing Touch Panel.

Touch panels are deemed as a critical platform for the future of human--computer interaction. Recently, flexible touch panels have attracted much attention due to their superior adhesivity and integratability to the human body. However, hydrogel- or organogel-based devices suffer from instability due to liquid evaporation or low-conductivity substrates. It demands an alternative functional touch panel featuring temperature tolerance, high conductivity, and stretchability. Here, we introduce an eutectogel by immobilizing a novel deep eutectic solvent (DES) within 2-hydroxyethyl acrylate (HEA) covalently cross-linked polymer scaffolds. In this DES (ethylene carbonate(EC)-LiTFSI), the C═O group of EC is unique as an electron donor exhibiting strong coordination interactions with Li+, promoting the dissociation of Li+ from LiTFSI to achieve excellent conductivity. Benefiting from their traits, eutectogel presents high conductivity, transmittance, antifreezing, and mechanical strength. In addition, using the surface-capacitive sensing mechanism, the eutectogel can be designed as a 1D strip and 2D rectangular touch panel which can achieve high-resolution touching tracks, even in a low-temperature environment and pressure-then-recovered state. This eutectogel strategy is envisioned to facilitate the development of next-generation intelligent devices, especially in extreme stretching and low-temperature application scenarios.