Molecular Engineering of Bright NIR-I/NIR-II Nanofluorophores for High-Resolution Bioimaging and Tumor Detection in Vivo.

A comprehensive approach for the construction of NIR-I/NIR-II nanofluorophores with exceptional brightness and excellent chemo- and photostability has been developed. This study first confirmed that the amphiphilic molecules with stronger hydrophobic moieties and weaker hydrophilic moieties are superior candidates for constructing brighter nanofluorophores, which are attributed to its higher efficiency in suppressing the intramolecular charge transfer/aggregation-caused fluorescence quenching of donor-acceptor-donor type fluorophores. The prepared nanofluorophore demonstrates a fluorescence quantum yield exceeding 4.5% in aqueous solution and exhibits a strong NIR-II tail emission up to 1300 nm. The superior performance of the nanofluorophore enabled the achievement of high-resolution whole-body vessel imaging and brain vessel imaging, as well as high-contrast fluorescence imaging of the lymphatic system in vivo. Furthermore, their potential for highly sensitive fluorescence detection of tiny tumors in vivo has been successfully confirmed, thus supporting their future applications in precise fluorescence imaging-guided surgery in the early stages of cancer.

A novel imprinted locus on bovine chromosome 18 homologous with human chromosome 16q24.1.

Genomic imprinting is an epigenetic regulation mechanism in mammals resulting in the parentally dependent monoallelic expression of genes. Imprinting disorders in humans are associated with several congenital syndromes and cancers and remain the focus of many medical studies. Cattle is a better model organism for investigating human embryo development than mice. Imprinted genes usually cluster on chromosomes and are regulated by different methylation regions (DMRs) located in imprinting control regions that control gene expression in cis. There is an imprinted locus on human chromosome 16q24.1 associated with congenital lethal developmental lung disease in newborns. However, genomic imprinting on bovine chromosome 18, which is homologous with human chromosome 16 has not been systematically studied. The aim of this study was to analyze the allelic expressions of eight genes (CDH13, ATP2C2, TLDC1, COTL1, CRISPLD2, ZDHHC7, KIAA0513, and GSE1) on bovine chromosome 18 and to search the DMRs associated gene allelic expression. Three transcript variants of the ZDHHC7 gene (X1, X2, and X5) showed maternal imprinting in bovine placentas. In addition, the monoallelic expression of X2 and X5 was tissue-specific. Five transcripts of the KIAA0513 gene showed tissue- and isoform-specific monoallelic expression. The CDH13, ATP2C2, and TLDC1 genes exhibited tissue-specific imprinting, however, COTL1, CRISLPLD2, and GSE1 escaped imprinting. Four DMRs, established after fertilization, were found in this region. Two DMRs were located between the ZDHHC7 and KIAA0513 genes, and two were in exon 1 of the CDH13 and ATP2C2 genes, respectively. The results from this study support future studies on the molecular mechanism to regulate the imprinting of candidate genes on bovine chromosome 18.

In Situ Sodium Chloride Cross-Linked Fish Skin Collagen Scaffolds for Functional Hemostasis Materials.

Current fish collagen hemostasis for wound healing products is commonly obtained by electrospinning or artificial cross-linking fish collagen fibers which lacks mechanical properties, and biofunctions. Here, a new bio-active fish skin scaffold (FSS) is shown using in situ cross-linked scaleless freshwater fish skin adding adipose-derived stem cells (ASCs)-produced exosomes for hemostasis and wound healing. The structure, pore size, and the thickness of FSS is studied by swelling test, Fourier-transform infrared (FT-IR) spectra, scanning electron microscope (SEM) images, and histological analysis. The biofunctions of the FSS are also tested in vitro and in vivo. FSS keeps two functional layers: The dermis layer collagen forms a sponge like structure after swelling and in situ cross-linking treatments. The pore size of the FSS is ≈152 ± 23.54 µm, which is suitable for cells growing, angiogenesis and ASCs exosomes accelerate wound healing. The fat-rich epidermis layer can keep the wound moisty and clean before completely healed. In vitro and in vivo experimental results indicate that FSS+Exosomes enhances rat skin cavity wound healing. In situ sodium chloride cross-linked FSS+Exosomes provides a new strategy as functional hemostatic dressing scaffold for wound healing.

Functional MXenes: Progress and Perspectives on Synthetic Strategies and Structure-Property Interplay for Next-Generation Technologies.

MXenes are a class of 2D materials that include layered transition metal carbides, nitrides, and carbonitrides. Since their inception in 2011, they have garnered significant attention due to their diverse compositions, unique structures, and extraordinary properties, such as high specific surface areas and excellent electrical conductivity. This versatility has opened up immense potential in various fields, catalyzing a surge in MXene research and leading to note worthy advancements. This review offers an in-depth overview of the evolution of MXenes over the past 5 years, with an emphasis on synthetic strategies, structure-property relationships, and technological prospects. A classification scheme for MXene structures based on entropy is presented and an updated summary of the elemental constituents of the MXene family is provided, as documented in recent literature. Delving into the microscopic structure and synthesis routes, the intricate structure-property relationships are explored at the nano/micro level that dictate the macroscopic applications of MXenes. Through an extensive review of the latest representative works, the utilization of MXenes in energy, environmental, electronic, and biomedical fields is showcased, offering a glimpse into the current technological bottlenecks, such asstability, scalability, and device integration. Moreover, potential pathways for advancing MXenes toward next-generation technologies are highlighted.

HBV PreC interacts with SUV39H1 to induce viral replication by blocking the proteasomal degradation of viral polymerase.

Hepatitis B e antigen (HBeAg) seropositivity during the natural history of chronic hepatitis B (CHB) is known to coincide with significant increases in serum and intrahepatic HBV DNA levels. However, the precise underlying mechanism remains unclear. In this study, we found that PreC (HBeAg precursor) genetic ablation leads to reduced viral replication both in vitro and in vivo. Furthermore, PreC impedes the proteasomal degradation of HBV polymerase, promoting viral replication. We discovered that PreC interacts with SUV39H1, a histone methyltransferase, resulting in a reduction in the expression of Cdt2, an adaptor protein of CRL4 E3 ligase targeting HBV polymerase. SUV39H1 induces H3K9 trimethylation of the Cdt2 promoter in a PreC-induced manner. CRISPR-mediated knockout of endogenous SUV39H1 or pharmaceutical inhibition of SUV39H1 decreases HBV loads in the mouse liver. Additionally, genetic depletion of Cdt2 in the mouse liver abrogates PreC-related HBV replication. Interestingly, a negative correlation of intrahepatic Cdt2 with serum HBeAg and HBV DNA load was observed in CHB patient samples. Our study thus sheds light on the mechanistic role of PreC in inducing HBV replication and identifies potential therapeutic targets for HBV treatment.

Deep ultraviolet laser at 223.8†nm with adjustable repetition rate and narrow pulse width.

We presented the first, to our knowledge, demonstration of an ultraviolet (UV) laser at 223.8 nm by six-harmonic generation of an electro-optic Q-switched cavity dumping 1342 nm Nd:YVO4 laser. It offers high power, constant short pulse duration, and adjustable pulse repetition rate. The pulse duration is independent of the pump power and repetition rate compared to classical Q-switched oscillators. The output efficiency of the UV laser is optimized by adjusting the focusing lens. With the incident pump power of 30 W, an maximum average output power of 249 mW was obtained at 13 kHz. The pulse width maintained 3.4-3.5 ns from 5 to 20 kHz. The maximum pulse energy of 28.1 µJ was obtained at 5 kHz, and the corresponding peak power was up to 8.1 kW.

Psychological resilience in the relationship between family function and illness uncertainty among family members of trauma patients in the intensive care unit.

BACKGROUND: Severe trauma accounts for a main factor inducing mortality for individuals aged < 45 years in China, which requires admission to intensive care unit (ICU) to receive comprehensive treatment. Family members of patients with unanticipated and life-threatening trauma during their ICU stays often experience psychosocial distress due to illness uncertainty. Previous research has shown that family function and psychological resilience are associated with illness uncertainty, respectively. However, little is known about the current situation and interacting mechanism between family function, psychological resilience, and illness uncertainty of family members for ICU trauma patients. Therefore, this study focused on exploring the current situation and relationships between these three factors in family members for ICU trauma patients. METHODS: The convenience sampling approach was adopted in the present cross-sectional survey, which involved 230 family members for ICU trauma patients from 34 hospitals in Chongqing, China. Related data were extracted with self-reporting questionnaires, which included sociodemographic characteristic questionnaire, the Family Adaptability, Partnership, Growth, Affection and Resolve Scale (APGAR), the 10-item Connor-Davidson Resilience Scale (10-CD-RISC) and the Mishel's Illness Uncertainty Scale for Family Members (MUIS-FM). Pearson correlation analysis was conducted to examine the correlations between various variables. Additionally, a structural equation model was adopted to assess the mediating effect of psychological resilience on family function and illness uncertainty. RESULTS: According to our results, family members for ICU trauma patients experienced high illness uncertainty with moderate family dysfunction and low psychological resilience. Family function directly affected illness uncertainty and indirectly affected illness uncertainty through psychological resilience in family members of ICU trauma patients. CONCLUSIONS: Family function and psychological resilience are the protective factors for reducing illness uncertainty. Healthcare providers should take effective measures, including family-functioning improvement and resilience-focused interventions, for alleviating illness uncertainty in family members of ICU trauma patients.

LncRNA ENSGALG00000021686 regulates fat metabolism in chicken hepatocytes via miR-146b/AGPAT2 pathway.

The liver contributes to lipid metabolism as the hub of fat synthesis. Long non-coding RNAs (lncRNAs) are considered the regulators of cellular processes. Since LncRNA ENSGALG00000021686 (lncRNA 21 686) has been described as a regulator of lipid metabolism, the present study aimed to clarify the role of lncRNA 21 686 in chicken hepatocytes' lipid metabolism. Thirty-two chickens were divided into four groups and were treated with diets containing different amounts of fat, and the hepatic expression of lncRNA 21 686 and miR-146b along with the levels of proteins involved in the regulation of fat metabolism, lipid indices and oxidative stress were measured. Moreover, primary chicken hepatocytes were transfected with lncRNA 21 686 small interfering RNA or microRNA (miRNA, miR)-146b mimics to measure the consequences of suppressing lncRNA or inducing miRNA expression on the levels of proteins involved in fat metabolism and stress markers. The results showed that the high-fat diet modulated the expression of lncRNA 21 686 and miR-146b (p-value < 0.001). Moreover, there was a significant increase in 1-acyl-sn-glycerol-3-phosphate acyltransferase 2 (AGPAT2) gene expression and protein levels and modulated fat-related markers. Furthermore, the results showed that lncRNA 21 686 suppression reduced the expression of AGPAT2 and its downstream proteins (p-value < 0.05). Overexpression of miR-146b regulated fat metabolism indicator expression. Transfection experiments revealed that lncRNA 21 686 suppression increased miR-146b expression. The findings suggested a novel mechanism containing lncRNA 21 686/miR-146b/AGPAT2 in the regulation of fat metabolism in chicken hepatocytes.

The landscape of allelic expression and DNA methylation at the bovine SGCE/PEG10 locus.

Genomic imprinting is an epigenetic regulation in mammals in which a small subset of genes is monoallelically expressed dependent on their parental origin. A large imprinted domain, SGCE/PEG10 locus, is located on human chromosome 7q21s and mouse proximal chromosome 6. However, genomic imprinting of bovine SGCE/PEG10 cluster has not been systematically studied. In this study, we investigated allele expression of 14 genes of the SGCE/PEG10 locus in bovine somatic tissues and term placenta using a single nucleotide polymorphism (SNP)-based sequencing method. In addition to SGCE and PEG10, two conserved paternally expressed genes in human and mice, five other genes (TFPI2, GNG11, ASB4, PON1, and PON3) were paternally expressed. Three genes, BET1, COL1A2, and CASD1, exhibited tissue-specific monoallelic expression. CALCR showed monoallelic expression in tissues but biallelic expression in the placenta. Three genes, GNGT1, PPP1R9A, and PON2, showed biallelic expression in cattle. Five differentially methylated regions (DMRs) were found to be associated with the allelic expression of TFPI2, COL1A2, SGCE/PEG10, PON3, and ASB4 genes, respectively. The SGCE/PEG10 DMR is a maternally hypermethylated germline DMR, but TFPI2, COL1A2, PON3, and ASB4 DMRs are secondary DMRs. In summary, we identified five novel bovine imprinted genes (GNG11, BET1, COL1A2, CASD1, and PON1) and four secondary DMRs at the SGCE/PEG10 locus.

Sarcopenia, sarcopenic obesity and the clinical outcome of the older inpatients with COVID-19 infection: a prospective observational study.

OBJECTIVE: We aimed to investigate the impact of sarcopenia and sarcopenic obesity (SO) on the clinical outcome in older patients with COVID-19 infection and chronic disease. METHODS: We prospectively collected data from patients admitted to Huadong Hospital for COVID-19 infection between November 1, 2022, and January 31, 2023. These patients were included from a previously established comprehensive geriatric assessment (CGA) cohort. We collected information on their pre-admission condition regarding sarcopenia, SO, and malnutrition, as well as their medical treatment. The primary endpoint was the incidence of intubation, while secondary endpoints included in-hospital mortality rates. We then utilized Kaplan-Meier (K-M) survival curves and the log-rank tests to compare the clinical outcomes related to intubation or death, assessing the impact of sarcopenia and SO on patient clinical outcomes. RESULTS: A total of 113 patients (age 89.6 ± 7.0 years) were included in the study. Among them, 51 patients had sarcopenia and 39 had SO prior to hospitalization. Intubation was required for 6 patients without sarcopenia (9.7%) and for 18 sarcopenia patients (35.3%), with 16 of these being SO patients (41%). Mortality occurred in 2 patients without sarcopenia (3.3%) and in 13 sarcopenia patients (25.5%), of which 11 were SO patients (28%). Upon further analysis, patients with SO exhibited significantly elevated risks for both intubation (Hazard Ratio [HR] 7.43, 95% Confidence Interval [CI] 1.26-43.90, P < 0.001) and mortality (HR 6.54, 95% CI 1.09-39.38, P < 0.001) after adjusting for confounding factors. CONCLUSIONS: The prevalence of sarcopenia or SO was high among senior inpatients, and both conditions were found to have a significant negative impact on the clinical outcomes of COVID-19 infection. Therefore, it is essential to regularly assess and intervene in these conditions at the earliest stage possible.

NLRP3 regulates CIITA/MHC II axis and interferon-γ-inducible chemokines in Malassezia globosa-infected keratinocytes.

CIITA, a member of NOD-like receptor (NLR) family, is the major MHC II trans-activator and mediator of Th1 immunity, but its function and interaction with NLRP3 have been little studied. We found activation of NLRP3 inflammasome, increased expression of CIITA, CBP, pSTAT1, STAT1, MHC II, IFN-γ and IFN-γ-inducible chemokines (CCL1 and CXCL8), and colocalisation of NLRP3 with CIITA in Malassezia folliculitis lesions, Malassezia globosa-infected HaCaT cells and mouse skin. CoIP with anti-CIITA or anti-NLRP3 antibody pulled down NLRP3 or both CIITA and ASC. NLRP3 silencing or knockout caused CIITA downexpression and their colocalisation disappearance in HaCaT cells and mouse skin of Nlrp3-/- mice, while CIITA knockdown had no effect on NLRP3, ASC, IL-1ß and IL-18 expression. NLRP3 inflammasome inhibitors and knockdown significantly suppressed IFN-γ, CCL1, CXCL8 and CXCL10 levels in M. globosa-infected HaCaT cells. CCL1 and CXCL8 expression was elevated in Malassezia folliculitis lesions and reduced in Nlrp3-/- mice. These results demonstrate that M. globosa can activate NLRP3 inflammasome, CIITA/MHC II signalling and IFN-γ-inducible chemokines in human keratinocytes and mouse skin. NLRP3 may regulate CIITA by their binding and trigger Th1 immunity by secreting CCL1 and CXCL8/IL-8, contributing to the pathogenesis of Malassezia-associated skin diseases.

A highly sensitive fluorescence biosensor for aflatoxins B1 detection based on polydiacetylene liposomes combined with exonuclease III-assisted recycling amplification.

A fluorescence biosensor for determination of aflatoxin B1 (AFB1) based on polydiacetylene (PDA) liposomes and exonuclease III (EXO III)-assisted recycling amplification was developed. The AFB1 aptamer partially hybridizes with complementary DNA (cDNA), which is released upon recognition of AFB1 by the aptamer. Subsequently, the cDNA hybridizes with hairpin H to form double-stranded DNA that undergoes digestion by EXO III, resulting in the cyclic release of cDNA and generation of capture DNA for further reaction. The capture DNA then hybridizes with probe modified on PDA liposomes, leading to aggregation of liposomes and subsequent fluorescence production. This strategy exhibited a limit of detection of 0.18 ng/mL within the linear range 1-100 ng/mL with a determination coefficient > 0.99. The recovery ranged from 92.81 to 106.45%, with relative standard deviations (RSD) between 1.73 and 4.26%, for corn, brown rice, peanut butter, and wheat samples. The stability, accuracy, and specificity of the method demonstrated the applicability for real sample analysis.

Oxygen-deficient AgIO3 for efficiently photodegrading organic contaminants under natural sunlight.

Defect engineering is regarded as an effective strategy to boost the photo-activity of photocatalysts for organic contaminants removal. In this work, abundant surface oxygen vacancies (Ov) are created on AgIO3 microsheets (AgIO3-OV) by a facile and controllable hydrogen chemical reduction approach. The introduction of surface Ov on AgIO3 broadens the photo-absorption region from ultraviolet to visible light, accelerates the photoinduced charges separation and migration, and also activates the formation of superoxide radicals (•O2-). The AgIO3-OV possesses an outstanding degradation rate constant of 0.035 min-1, for photocatalytic degrading methyl orange (MO) under illumination of natural sunlight with a light intensity is 50 mW/cm2, which is 7 and 3.5 times that of the pristine AgIO3 and C-AgIO3 (AgIO3 is calcined in air without generating Ov). In addition, the AgIO3-OV also exhibit considerable photoactivity for degrading other diverse organic contaminants, including azo dye (rhodamine B (RhB)), antibiotics (sulflsoxazole (SOX), norfloxacin (NOR), chlortetracycline hydrochloride (CTC), tetracycline hydrochloride (TC) and ofloxacin (OFX)), and even the mixture of organic contaminants (MO-RhB and CTC-OFX). After natural sunlight illumination for 50 min, 41.4% of total organic carbon (TOC) for MO-RhB mixed solution can be decreased over AgIO3-OV. In a broad range of solution pH from 3 to 11 or diverse water bodies of MO solution, AgIO3-OV exhibits attractive activity for decomposing MO. The MO photo-degradation process and mechanism over AgIO3-OV under natural sunlight irradiation has been systemically investigated and proposed. The toxicities of MO and its degradation intermediates over AgIO3-OV are compared using Toxicity Estimation Software (T.E.S.T.). Moreover, the non-toxicity of both AgIO3-OV catalyst and treated antibiotic solution (CTC-OFX mixture) are confirmed by E. coli DH5a cultivation test, supporting the feasibility of AgIO3-OV catalyst to treat organic contaminants in real water under natural sunlight illumination.

Enhanced and Sustainable Removal of Indoor Formaldehyde by Naturally Porous Bamboo Activated Carbon Supported with MnOx: Synergistic Effect of Adsorption and Oxidation.

Novel bamboo activated carbon (BAC) catalysts decorated with manganese oxides (MnOx) were prepared with varying MnOx contents through a facile one-step redox reaction. Due to the physical anchoring effect of the natural macropore structure for catalyst active components, homogeneous MnOx nanoparticles (NPs), and high specific surface area over catalyst surface, the BAC@MnOx-N (N = 1, 2, 3, 4, 5) catalyst shows encouraging adsorption and catalytic oxidation for indoor formaldehyde (HCHO) removal at room temperature. Dynamic adsorption and catalytic activity experiments were conducted. The higher Smicro (733 m2/g) and Vmicro/Vt (82.6%) of the BAC@MnOx-4 catalyst could facilitate its excellent saturated and breakthrough adsorption capacity (5.24 ± 0.42 mg/g, 2.43 ± 0.22 mg/g). The best performer against 2 ppm HCHO is BAC@MnOx-4 catalyst, exhibiting a maximum HCHO removal efficiency of 97% for 17 h without any deactivation as RH = 0, which is higher than those of other MnOx-based catalysts. The average oxidation state and in situ DRIFTS analysis reveal that abundant oxygen vacancies on the BAC@MnOx-4 catalyst could be identified as surface-active sites of decomposing HCHO into the intermediate species (dioxymethylene and formate). This study provides a potential approach to deposit MnOx nanoparticles onto the BAC surface, and this hybrid BAC@MnOx material is promising for indoor HCHO removal at room temperature.

Functional Group-driven Competing Mechanism in Electrochemical Reaction and Adsorption/Desorption Processes toward High-capacity Aluminum-Porphyrin Batteries.

Nonaqueous organic aluminum batteries are considered as promising high-safety energy storage devices due to stable ionic liquid electrolytes and Al metals. However, the stability and capacity of organic positive electrodes are limited by their inherent high solubility and low active organic molecules. To address such issues, here porphyrin compounds with rigid molecular structures present stable and reversible capability in electrochemically storing AlCl2+. Comparison between the porphyrin molecules with electron-donating groups (TPP-EDG) and with electron-withdrawing groups (TPP-EWG) suggests that EDG is responsible for increasing both HOMO and LUMO energy levels, resulting in decreased redox potentials. On the other hand, EWG is associated with decreasing both HOMO and LUMO energy levels, leading to promoted redox potentials. EDG and EWG play critical roles in regulating electron density of porphyrin π bond and electrochemical energy storage kinetics behavior. The competitive mechanism between electrochemical redox reaction and de/adsorption processes suggests that TPP-OCH3 delivers the highest specific capacity ~171.8 mAh g-1, approaching a record in the organic Al batteries.

Distinct brain state dynamics of native and second language processing during narrative listening in late bilinguals.

The process of complex cognition, which includes language processing, is dynamic in nature and involves various network modes or cognitive modes. This dynamic process can be manifested by a set of brain states and transitions between them. Previous neuroimaging studies have shed light on how bilingual brains support native language (L1) and second language (L2) through a shared network. However, the mechanism through which this shared brain network enables L1 and L2 processing remains unknown. This study examined this issue by testing the hypothesis that L1 and L2 processing is associated with distinct brain state dynamics in terms of brain state integration and transition flexibility. A group of late Chinese-English bilinguals was scanned using functional magnetic resonance imaging (fMRI) while listening to eight short narratives in Chinese (L1) and English (L2). Brain state dynamics were modeled using the leading eigenvector dynamic analysis framework. The results show that L1 processing involves more integrated states and frequent transitions between integrated and segregated states, while L2 processing involves more segregated states and fewer transitions. Our work provides insight into the dynamic process of narrative listening comprehension in late bilinguals and sheds new light on the neural representation of language processing and related disorders.

Liquid biopsy at the frontier in renal cell carcinoma: recent analysis of techniques and clinical application.

Renal cell carcinoma (RCC) is a major pathological type of kidney cancer and is one of the most common malignancies worldwide. The unremarkable symptoms of early stages, proneness to postoperative metastasis or recurrence, and low sensitivity to radiotherapy and chemotherapy pose a challenge for the diagnosis and treatment of RCC. Liquid biopsy is an emerging test that measures patient biomarkers, including circulating tumor cells, cell-free DNA/cell-free tumor DNA, cell-free RNA, exosomes, and tumor-derived metabolites and proteins. Owing to its non-invasiveness, liquid biopsy enables continuous and real-time collection of patient information for diagnosis, prognostic assessment, treatment monitoring, and response evaluation. Therefore, the selection of appropriate biomarkers for liquid biopsy is crucial for identifying high-risk patients, developing personalized therapeutic plans, and practicing precision medicine. In recent years, owing to the rapid development and iteration of extraction and analysis technologies, liquid biopsy has emerged as a low cost, high efficiency, and high accuracy clinical detection method. Here, we comprehensively review liquid biopsy components and their clinical applications over the past 5 years. Additionally, we discuss its limitations and predict its future prospects.

Intentional Watch and Wait or Organ Preservation Surgery Following Neoadjuvant Chemoradiotherapy Plus Consolidation CAPEOX for MRI-defined Low-risk Rectal Cancer: Findings From a Prospective Phase 2 Trial (PKUCH-R01 Trial, NCT02860234).

OBJECTIVE: To assess the efficacy and safety of intentional watch and wait (W&W) and organ preservation surgery following neoadjuvant chemoradiotherapy plus consolidation CAPEOX in magnetic resonance imaging (MRI)-defined low-risk rectal cancer. BACKGROUND: Clinical T2/early T3 rectal cancers can achieve high yield pathological complete response (ypCR) rates after chemoradiotherapy; thus, an intentional W&W or organ preservation strategy for good clinical responders in these subgroups can be further tested. METHODS: This prospective, single-arm, phase 2 trial enrolled patients with low-risk MRI prestaged rectal cancers, who concurrently received chemoradiation, followed by four 3-weekly cycles of CAPEOX regimen. Following reassessment, clinical complete response (cCR) or near-cCR patients underwent W&W/organ preservation surgery; the primary endpoint was a 3-year organ preservation rate. RESULTS: Of the 64 participants, 58 completed treatment, with 6.4% and 33.9% grade 3 to 4 toxicities in the radiotherapy and consolidation CAPEOX phases, respectively, during a median 39.5-month follow-up. Initial cCR, and non-cCR occurred in 33, 13, and 18 patients, respectively. Of the 31 cCR and 7 near-cCR cases managed by W&W, local regrowth occurred in 7; of these, 6 received salvage surgery. The estimated 2-year local regrowth rates were 12.9% [95% confidence interval (CI): 1.1%-24.7%] in cCR and 42.9% (95% CI: 6.2%-79.6%) in near-cCR cases, respectively. Eight patients received local excision, including 2 with regrowth salvage. Lung metastases occurred in 3 patients and multiple metastasis occurred in 1 patient; no local recurrence occurred. The estimated 3-year organ preservation rate was 67.2% (95% CI: 55.6%-78.8%). The estimated 3-year cancer-specific survival, non-regrowth disease-free survival, and stoma-free survival were 96.6% (95% CI: 92.1%-100%), 92.2% (95% CI: 85.5%-98.9%), and 82.7% (95% CI: 73.5%-91.9%), respectively. CONCLUSIONS: Chemoradiotherapy plus consolidation CAPEOX for MRI-defined low-risk rectal cancer can lead to high rates of organ preservation through intentional W&W or local excision. The oncologic safety of this strategy should be further tested.

Tailoring Oxidation Responsiveness of Gold Nanoclusters via Ligand Engineering for Imaging Acute Kidney Injury.

Gold nanoclusters (AuNCs) have shown great promise for in vivo imaging because of their definable structure, tunable photoluminescence (PL), and desired renal clearance. However, current understanding of the responsiveness of AuNCs to biological substances is still limited, which may hamper their biomedical applications. Herein, we explore the oxidation responsiveness of near-infrared II (NIR-II) luminescent AuNCs capped with two different ligands, which can be optimized for high-efficiency NIR-II PL imaging of mice acute kidney injury (AKI) featuring high-level peroxynitrite anions (ONOO-). We found that in the presence of ONOO-, N-acetylcysteine-capped AuNCs (NAC-AuNCs) tended to be oxidized more easily than that capped with the macromolecular mercapto-ß-cyclodextrin (CDS-AuNCs), resulting in the aggregation of NAC-AuNCs into large-sized assemblies, which was not observed in CDS-AuNCs. The oxidation-triggered morphology, composition, and NIR-II PL changes in NAC-AuNCs were then systematically studied. We finally demonstrated that NAC-AuNCs can be implemented for sensitive NIR-II PL imaging of mice AKI, facilitated by the synergetic in situ AuNC aggregation and decreased glomerular filtration rate (GFR) in the injured kidney, which outperforms the methods solely based on the decreased GFR effect. Therefore, this work highlights the critical significance of ligand engineering in AuNCs and may motivate future design of AuNCs for diverse bioimaging applications.

Origin of adaptations to open environments and social behaviour in sabretoothed cats from the northeastern border of the Tibetan Plateau.

The iconic sabretooth Homotherium is thought to have hunted cooperatively, but the origin of this behaviour and correlated morphological adaptations are largely unexplored. Here we report the most primitive species of Amphimachairodus (Amphimachairodus hezhengensis sp. nov.), a member of Machairodontini basal to Homotherium, from the Linxia Basin, northeastern border of the Tibetan Plateau (9.8-8.7 Ma). The long snout, laterally oriented and posteriorly located orbit of Amphimachairodus suggest a better ability to observe the surrounding environment, rather than targeting single prey, pointing to an adaptation to the open environment or social behaviour. A pathological forepaw of Amphimachairodus provides direct evidence of partner care. Our analyses of trait evolutionary rates support that traits correlated with killing behaviour and open environment adaptation evolved prior to other traits, suggesting that changes in hunting behaviour may be the major evolutionary driver in the early evolution of the lineage. A. hezhengensis represents one of the most important transitions in the evolution of Machairodontini, leading to adaptation in open environments and contributing to their further dispersal and radiation worldwide. This rapid morphological change is likely to be correlated with increasingly arid environments caused by the rise of the Tibetan Plateau, and competition from abundant large carnivores in this area.