The role of intestinal flora on tumor immunotherapy: recent progress and treatment implications.

Immunotherapy, specifically immune checkpoint inhibitors, has emerged as a promising approach for treating malignant tumors. The gut, housing approximately 70 % of the body's immune cells, is abundantly populated with gut bacteria that actively interact with the host's immune system. Different bacterial species within the intestinal flora are in a delicate equilibrium and mutually regulate each other. However, when this balance is disrupted, pathogenic microorganisms can dominate, adversely affecting the host's metabolism and immunity, ultimately promoting the development of disease. Emerging researches highlight the potential of interventions such as fecal microflora transplantation (FMT) to improve antitumor immune response and reduce the toxicity of immunotherapy. These remarkable findings suggest the major role of intestinal flora in the development of cancer immunotherapy and led us to the hypothesis that intestinal flora transplantation may be a new breakthrough in modifying immunotherapy side effects.

Lifetime cumulative effect of reproductive factors on ischaemic heart disease in a prospective cohort.

OBJECTIVE: This study aimed to examine the association between lifetime oestrogen exposure and ischaemic heart disease (IHD), based on the hypothesis that higher lifetime oestrogen exposure is linked to lower cardiovascular risk. METHODS: In 2004-2008, lifetime cumulative exposure to reproductive factors was assessed among postmenopausal females from the China Kadoorie Biobank using reproductive lifespan (RLS), endogenous oestrogen exposure (EEE) and total oestrogen exposure (TEE). EEE was calculated by subtracting pregnancy-related and contraceptive use duration from RLS, while TEE by adding up the same components except for lactation. Incident IHD during follow-up (2004-2015) was identified. Stratified Cox proportional hazards models estimated the HRs and 95% CIs of IHD for RLS, EEE and TEE. RESULTS: Among 118 855 postmenopausal females, 13 162 (11.1%) developed IHD during a median follow-up of 8.9 years. The IHD incidence rates were 13.0, 12.1, 12.5, 13.8 per 1000 person-years for RLS Q1-Q4, 15.8, 12.6, 11.3, 12.1 per 1000 person-years for EEE Q1-Q4 and 13.7, 12.3, 12.2, 13.4 per 1000 person-years for TEE Q1-Q4. The highest quartile (Q4) of RLS and TEE were associated with lower risks of IHD (adjusted HR (aHR) 0.95, 95% CI 0.91 to 1.00 and 0.92, 95% CI 0.88 to 0.97, respectively) compared with the lowest quartile (Q1). Longer EEE showed progressively lower risks of incident IHD (aHR 0.93, 95% CI 0.88 to 0.97; 0.88, 95% CI 0.84 to 0.93; 0.87, 95% CI 0.83 to 0.92 for Q2-Q4 vs Q1). CONCLUSIONS: Longer RLS, TEE and EEE were associated with lower risks of IHD among Chinese postmenopausal females.

Olaparib enhances radiation-induced systemic anti-tumor effects via activating STING-chemokine signaling in hepatocellular carcinoma.

Although Poly (ADP-ribose) polymerase (PARP) inhibitors have been clinically approved for cancers with BRCA mutations and are known to augment radiotherapy responses, their roles in promoting the abscopal effect and mediating immunotherapy in BRCA-proficient hepatocellular carcinoma (HCC) remain underexplored. Our study elucidates that olaparib enhances the radio-sensitivity of HCC cells. Coadministration of olaparib and irradiation induces significant DNA damage by generating double-strand breaks (DSBs), as revealed both in vitro and in immune-deficient mice. These DSBs activate the cGAS-STING pathway, initiating immunogenic cell death in abscopal tumors. STING activation reprograms the immune microenvironment in the abscopal tumors, triggering the release of type I interferon and chemokines, including CXCL9, CXCL10, CXCL11, and CCL5. This in turn amplifies T cell priming against tumor neoantigens, leading to an influx of activated, neoantigen-specific CD8+ T-cells within the abscopal tumors. Furthermore, olaparib attenuated the immune exhaustion induced by radiation and enhances the responsiveness of HCC to immune checkpoint inhibitors. Collectively, our data advocate that a synergistic regimen of PARP inhibitors and radiotherapy can strategically reinforce both local (primary) and systemic (abscopal) tumor control, bolstering HCC susceptibility to immunotherapy.

A Bioorthogonal Antidote Against the Photosensitivity after Photodynamic Therapy.

As an effective and non-invasive treatment modality for cancer, photodynamic therapy (PDT) has attracted considerable interest. With the recent advances in the photosensitizing agents, the fiber-optic systems, and other aspects, its application is extended to a wide range of superficial and localized cancers. However, for the few clinically used photosensitizers, most of them suffer from the drawback of causing prolonged photosensitivity after the treatment. As a result, post-PDT management is also a crucial issue. Herein, a facile bioorthogonal approach is reported that can effectively suppress this common side effect of PDT in nude mice. It involves the use of an antidote that contains a black-hole quencher BHQ-3 conjugated with a bicyclo[6.1.0]non-4-yne (BCN) moiety and a tetrazine-substituted boron dipyrromethene-based photosensitizer. By using tumor-bearing nude mice as an animal model, it is demonstrated that after PDT with this photosensitizer, the administration of the antidote can effectively quench the photodynamic activity of the residual photosensitizer by bringing the BHQ-3 quencher close to the photosensitizing unit through a rapid click reaction. It results in substantial reduction in skin damage upon light irradiation. The overall results demonstrate that this simple and facile strategy can provide an effective means for minimizing the photosensitivity after PDT.

Delta radiomics analysis for prediction of intermediary- and high-risk factors for patients with locally advanced cervical cancer receiving neoadjuvant therapy.

This study aimed to assess the feasibility of using magnetic resonance imaging (MRI)-based Delta radiomics characteristics extrapolated from the Ax LAVA + C series to identify intermediary- and high-risk factors in patients with cervical cancer undergoing surgery following neoadjuvant chemoradiotherapy. A total of 157 patients were divided into two groups: those without any intermediary- or high-risk factors and those with one intermediary-risk factor (negative group; n = 75). Those with any high-risk factor or more than one intermediary-risk factor (positive group; n = 82). Radiomics characteristics were extracted using Ax-LAVA + C MRI sequences. The data was divided into training (n = 126) and test (n = 31) sets in an 8:2 ratio. The training set data features were selected using the Mann-Whitney U test and the Least Absolute Shrinkage and Selection Operator (LASSO) test. The best radiomics features were then analyzed to build a preoperative predictive radiomics model for predicting intermediary- and high-risk factors in cervical cancer. Three models-the clinical model, the radiomics model, and the combined clinic and radiomics model-were developed in this study utilizing the random forest Algorithm. The receiver operating characteristic (ROC) curve, decision curve analysis (DCA), accuracy, sensitivity, and specificity were used to assess the predictive efficacy and clinical benefits of each model. Three models were developed in this study to predict intermediary- and high-risk variables associated with postoperative pathology for patients who underwent surgery after receiving neoadjuvant radiation. In the training and test sets, the AUC values assessed using the clinical model, radiomics model, and combined clinical and radiomics models were 0.76 and 0.70, 0.88 and 0.86, and 0.91 and 0.89, respectively. The use of machine learning algorithms to analyze Delta Ax LAVA + C MRI radiomics features can aid in the prediction of intermediary- and high-risk factors in patients with cervical cancer receiving neoadjuvant therapy.

Droplet attraction and coalescence mechanism on textured oil-impregnated surfaces.

Droplets residing on textured oil-impregnated surfaces form a wetting ridge due to the imbalance of interfacial forces at the contact line, leading to a wealth of phenomena not seen on traditional lotus-leaf-inspired non-wetting surfaces. Here, we show that the wetting ridge leads to long-range attraction between millimeter-sized droplets, which coalesce in three distinct stages: droplet attraction, lubricant draining, and droplet merging. Our experiments and model show that the magnitude of the velocity and acceleration at which droplets approach each other horizontally is the same as the vertical oil rise velocity and acceleration in the wetting ridge. Moreover, the droplet coalescence mechanism can be modeled using the classical mass-spring system. The insights gained from this work will inform future fundamental studies on remote droplet interaction on textured oil-impregnated surfaces for optimizing water harvesting and condensation heat transfer.

The reconstruction of fingertip injury by mini hallux toenail flap pedicled with the hallux transverse artery and toe pulp vein transplantation technique based on the equivalent design theory.

INTRODUCTION: How to reconstruct the damaged fingertip is a clinical problem. Our team propose the theory of equivalent design and use the mini toenail flap pedicled with the hallux transverse artery and toe pulp vein transplantation technique to reconstruct Allen's type II fingertip injury. Thus, we perform the retrospective study to evaluate the effects of this technique on fingertip injury. MATERIALS AND METHODS: A retrospective analysis was performed on 56 patients admitted to our hospital from January 2015 to January 2020 who used equivalently designed miniature hallux toenail flaps for the plastic repair of fingertip damage. We recorded the size of the miniature hallux toenail flap, operation time, intraoperative blood loss, and complications and calculated the survival rate of the transplanted miniature hallux toenail flap. During routine follow-up after surgery, we recorded nail growth time and observed finger appearance. At the last time of follow-up, we recorded Semmes-Weinstein evaluating tactile sensation and Two-point discrimination testing (TPD). The efficacy was evaluated by Zook score evaluation. RESULTS: The size of the mini hallux toenail flap was 0.71 cm × 1.22 cm to 0.88 cm × 1.71 cm. The operation time was (3.54 ± 0.58) hours, the intraoperative blood loss was (20.66 ± 4.87) ml, and the survival rate of mini hallux toenail flaps was 100%. The postoperative follow-up time was (30.82 ± 11.21) months, and the total nail growth time was (9.68 ± 2.11) months. The average tactile sensation evaluated by the Semmes-Weinstein test was (0.32 ± 0.14) g, and the average TPD was (7.33 ± 1.02) mm. According to Zook score, the curative effect of fifty-six cases were all excellent or good with 100% excellent and good rate, and all patients had beautiful appearances and good function of damaged fingertips. CONCLUSIONS: Based on the equivalent design theory, the mini hallux toenail flap pedicled with the hallux transverse artery and toe pulp vein transplantation technique is an effective method to reconstruct Allen's type II fingertip injury with a beautiful appearance and good function. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Femoral neck system vs. cannulated screws on treating femoral neck fracture: a meta-analysis and system review.

Objective: This meta-analysis aimed to compare the relative safety and efficacy of cannulated compression screw (CCS) and femoral neck system (FNS) in treating patients with femoral neck fractures and to provide evidence-based medical evidence for FNS in treating femoral neck fractures. Methods: PubMed, Embase, Cochrane, and China National Knowledge Infrastructure databases were searched to collect outcomes related to femoral neck fractures treated with FNS and CCS, including time to fracture healing, incidence of non-union, incidence of osteonecrosis of the femoral head, incidence of failure of internal fixation, rate of femoral neck shortening, Harris hip score, Barthel index, operative time, intraoperative blood loss, fluoroscopy frequency, and complications. A meta-analysis was performed using RevManv5.4 (The Cochrane Collaboration) and Stata v14.0 software. Results: This analysis included 21 studies involving 1,347 patients. The results showed that FNS was superior to CCS in terms of fracture healing time [mean difference (MD) = -0.75, 95% CI = (-1.04, -0.46), P < 0.05], incidence of bone non-union [odds ratio (OR) = 0.53, 95% CI = (0.29, 0.98), P = 0.04], incidence of osteonecrosis of the femoral head [OR = 0.49, 95% CI = (0.28, 0.86), P = 0.01], incidence of internal fixation failure [OR = 0.30, 95% CI = (0.18, 0.52), P < 0.05], rate of femoral neck shortening [OR = 0.38, 95% CI = (0.27, 0.54), P > 0.05], Harris hip score [MD = 3.31, 95% CI = (1.99, 4.63), P < 0.001], Barthel index [MD = 4.31, 95% CI = (3.02, 5.61), P < 0.05], intraoperative bleeding [MD = 14.72, 95% CI = (8.52, 20.92), P < 0.05], fluoroscopy frequency [OR = 0.53, 95% CI = (0.29, 0.98), P = 0.04], and complications [OR = 0.31, 95% CI = (0.22, 0.45), P < 0.05]. The difference between FNS and CCS in operative time was not statistically significant [MD = -2.41, 95% CI = (-6.88, 2.05), P = 0.29]. Conclusion: FNS treatment of femoral neck fracture can shorten the fracture healing time; reduce the incidence and translucent rate of bone non-union, osteonecrosis of the femoral head, and internal fixation failure; reduce intraoperative blood loss and postoperative complications; and improve hip joint function and activity. We are confident in the findings that FNS, an effective and safe procedure for internal fixation of femoral neck fractures, is superior to CCS.

Design and synthesis of a NAD(P)H:quinone oxidoreductase 1-activatable photosensitiser for controlled photodynamic therapy.

The utilisation of enzymes as stimuli can activate theranostic agents in a highly specific manner. We report herein a far-red-absorbing boron dipyrromethene-based photosensitiser that is responsive towards the cancer-associated human NAD(P)H:quinone oxidoreductase 1, enabling the controlled restoration of photodynamic activity for selective elimination of cancer cells.

Synergistic Benefits of Micro/Nanostructured Oil-Impregnated Surfaces in Reducing Fouling while Enhancing Heat Transfer.

Liquid-liquid heat exchangers that operate in marine environments are susceptible to biofouling, which decreases the overall heat exchange between hot and cold liquids by increasing the conduction resistance. Recently, micro/nanostructured oil-impregnated surfaces have been shown to significantly reduce biofouling. However, their potential as a heat exchanger material has not been studied. Neither is it obvious since the oil used for impregnation increases the wall thickness and the associated conduction resistance. Here, by conducting extensive field and laboratory studies supported by theoretical modeling of heat transfer in oil-infused heat exchanger tubes, we report the synergistic benefits of micro/nanostructured oil-impregnated surfaces for reducing biofouling while maintaining good heat transfer. These benefits justify the use of lubricant-infused surfaces as heat exchanger materials, in particular in marine environments.

Targeting Hippo pathway: A novel strategy for Helicobacter pylori-induced gastric cancer treatment.

The Hippo pathway plays an important role in cell proliferation, apoptosis, and differentiation; it is a crucial regulatory pathway in organ development and tumor growth. Infection with Helicobacter pylori (H. pylori) increases the risk of developing gastric cancer. In recent years, significant progress has been made in understanding the mechanisms by which H. pylori infection promotes the development and progression of gastric cancer via the Hippo pathway. Exploring the Hippo pathway molecules may yield new diagnostic and therapeutic targets for H. pylori-induced gastric cancer. The current article reviews the composition and regulatory mechanism of the Hippo pathway, as well as the research progress of the Hippo pathway in the occurrence and development of H. pylori-related gastric cancer, in order to provide a broader perspective for the study and prevention of gastric cancer.

Ineffective Effort in Patients With Acute Brain Injury Undergoing Invasive Mechanical Ventilation.

BACKGROUND: Ineffective effort (IE) is a frequent patient-ventilator asynchrony in invasive mechanical ventilation. This study aimed to investigate the incidence of IE and to explore its relationship with respiratory drive in subjects with acute brain injury undergoing invasive mechanical ventilation. METHODS: We retrospectively analyzed a clinical database that assessed patient-ventilator asynchrony in subjects with acute brain injury. IE was identified based on airway pressure, flow, and esophageal pressure waveforms collected at 15-min intervals 4 times daily. At the end of each data set recording, airway-occlusion pressure (P0.1) was determined by the airway occlusion test. IE index was calculated to indicate the severity of IE. The incidence of IE in different types of brain injuries as well as its relationship with P0.1 was determined. RESULTS: We analyzed 852 data sets of 71 subjects with P0.1 measured and undergoing mechanical ventilation for at least 3 d after enrollment. IE was detected in 688 (80.8%) data sets, with a median index of 2.2% (interquartile range 0.4-13.1). Severe IE (IE index ≥ 10%) was detected in 246 (28.9%) data sets. The post craniotomy for brain tumor and the stroke groups had higher median IE index and lower P0.1 compared with the traumatic brain injury group (2.6% [0.7-9.7] vs 2.7% [0.3-21] vs 1.2% [0.1-8.5], P = .002; 1.4 [1-2] cm H2O vs 1.5 [1-2.2] cm H2O vs 1.8 [1.1-2.8] cm H2O, P = .001). Low respiratory drive (P0.1 < 1.14 cm H2O) was independently associated with severe IE in the expiratory phase (IEE) even after adjusting for confounding factors by logistic regression analysis (odds ratio 5.18 [95% CI 2.69-10], P < .001). CONCLUSIONS: IE was very common in subjects with acute brain injury. Low respiratory drive was independently associated with severe IEE.

Nano-ferrihydrite colloidal particles mediated interfacial interactions of arsenate and cadmium: Implications for their fate under iron-rich geological settings.

Arsenic (As) and cadmium (Cd) often coexist in paddy soils. Nano-ferrihydrite colloidal particles (NFPs) are ubiquitous at redox active interfaces of the paddy system and are well-known to play a critical role in controlling the solubility and bio-availability of As and Cd. However, the mutual interaction between As and Cd on NFPs remains elusive. Herein, batch experiments and in-situ spectroscopic techniques were used to investigate the effects of the interaction pattern (sequential reaction) of Cd(II) and As(V) on their respective adsorption on the surfaces of NFPs. Two scenarios were designed: Cd(II) pre-saturated NFPs and As(V) pre-saturated NFPs. Adsorption of Cd(II) was increased by 1.67, 4.08, and 5.21 times in As(V)-saturated NFPs, but only by 1.05, 1.11, and 1.15 times for As(V) in Cd(II)-saturated NFPs. Further, we determined the pH-dependent mutually beneficial cooperation pathways as mediated by the surface of NFPs. At lower pH (5), As(V) tended to promote Cd(II) adsorption, whereas Cd(II) tended to enhance As(V) adsorption at higher pH (> 5.5). X-ray photoelectron spectroscopy (XPS) indicated that both pre-saturated Cd(II) and As(V) altered the local coordination environment of their counterpart ions. Furthermore, results from in-situ attenuated total reflection-Fourier-transform infrared spectroscopy (ATR-FTIR) and second derivative peak shape fitting revealed two types of ternary surface complexes, namely Cd(II)-bridged and As(V)-bridged complexes, which were responsible for the distinct Cd(II) and As(V) co-adsorption behavior on the surface of NFPs under different conditions. These findings help us understand how co-presence Cd and As behave in an iron-rich geological setting and will aid in the development of related restoration technologies.

Unique ice dendrite morphology on state-of-the-art oil-impregnated surfaces.

Due to its multifaceted impact in various applications, icing and ice dendrite growth has been the focus of numerous studies in the past. Dendrites on wetting (hydrophilic) and nonwetting (hydrophobic) surfaces are sharp, pointy, branching, and hairy. Here, we show a unique dendrite morphology on state-of-the-art micro/nanostructured oil-impregnated surfaces, which are commonly referred to as slippery liquid-infused porous surfaces or liquid-infused surfaces. Unlike the dendrites on traditional textured hydrophilic and hydrophobic surfaces, the dendrites on oil-impregnated surfaces are thick and lumpy without pattern. Our experiments show that the unique ice dendrite morphology on lubricant-infused surfaces is due to oil wicking into the porous dendritic network because of the capillary pressure imbalance between the surface texture and the dendrites. We characterized the shape complexity of the ice dendrites using fractal analysis. Experiments show that ice dendrites on textured oil-impregnated surfaces have lower fractal dimensions than those on traditional lotus leaf-inspired air-filled porous structures. Furthermore, we developed a regime map that can be used as a design guideline for micro/nanostructured oil-impregnated surfaces by capturing the complex effects of oil chemistry, oil viscosity, and wetting ridge volume on dendrite growth and morphology. The insights gained from this work inform strategies to reduce lubricant depletion, a major bottleneck for the transition of micro/nanostructured oil-impregnated surfaces from bench-top laboratory prototypes to industrial use. This work will assist the development of next-generation depletion-resistant lubricant-infused ice-repellent surfaces.

The ignored risk: heavy metal pollution of medicine and food homologous substances.

A survey was conducted to investigate the effects of cadmium (Cd), arsenic (As), chromium (Cr), lead (Pb), and copper (Cu) in medicine and food homologous substances (MFHs) on human health. Nine common and typical MFHs (Dendrobium, Bulbus lilii, Poria, Semen nelumbinis, Radix puerariae, Gardenia jasminoides, Hordeum vulgare L, Semen coicis, and Ganoderma Karst) in the form of medicinal slices ready for decoction were purchased from pharmacies. Five among the MFHs (Dendrobium, Bulbus lilii, Poria, Semen nelumbinis, and Radix puerariae) were further obtained from a local field as raw materials for comparison. The results showed that raw materials of MFHs collected from the field had higher contents of heavy metal and greater health risks than medicinal slices purchased from pharmacy. Generally, the heavy metal residues in MFHs of different medicinal parts were different, and MFHs from roots or stems had significantly higher contents of heavy metals than those from fruits or seeds. Most importantly, the contents of Cd in Bulbus lilii and As in wild Poria from field were higher than the contents described in the Pharmacopoeia of the People's Republic of China (ChP). Non-carcinogenic and carcinogenic risk assessments revealed that Poria from field had larger non-carcinogenic and carcinogenic risks to human health; Bulbus lilii showed no non-carcinogenic risk but exhibited carcinogenic risks, whereas Cr showed carcinogenic risks in all samples. Given that MFHs are incorporated in regular foods, care should be taken to minimize health hazards caused by heavy metals to human. This study creates awareness on the safety issues associated with MFHs, and provides basic information for establishing the maximum allowable contents of medicinal and food substances in normal diets.

FoxO3 restricts liver regeneration by suppressing the proliferation of hepatocytes.

Upon injury, the liver is capable of substantial regeneration from the original tissue until an appropriate functional size. The underlying mechanisms controlling the liver regeneration processes are not well elucidated. Previous studies have proposed that the transcription factor FoxO3 is involved in various liver diseases, but its exact role in the regulation of liver regeneration remains largely unclear. To directly test the detailed role of FoxO3 in liver regeneration, both a constitutive Albumin-Cre driver line and adeno-associated virus serotype 8 (AAV8)-Tbg-Cre (AAV-Cre)-injected adult FoxO3fl/fl mice were subjected to 70% partial hepatectomy (PH). Our data demonstrate that FoxO3 deletion accelerates liver regeneration primarily by limiting polyploidization and promoting the proliferation of hepatocytes during liver regeneration. RNA-seq analysis indicates that FoxO3 deficiency greatly alters the expression of gene sets associated with cell proliferation and apoptosis during liver regeneration. Chromatin immunoprecipitation-PCR (ChIP-PCR) and luciferase reporter assays reveal that FoxO3 promotes the expression of Nox4 but suppresses the expression of Nr4a1 in hepatocytes. AAV8 virus-mediated overexpression of Nox4 and knockdown of Nr4a1 significantly suppressed hepatocyte proliferation and liver regeneration in FoxO3-deficient mice. We demonstrate that FoxO3 negatively controls hepatocyte proliferation through Nox4 upregulation and Nr4a1 downregulation, thereby ensuring appropriate functional regeneration of the liver. Our findings provide novel mechanistic insight into the therapeutic mechanisms of FoxO3 in liver damage and repair.

Deep learning-enabled pelvic ultrasound images for accurate diagnosis of ovarian cancer in China: a retrospective, multicentre, diagnostic study.

BACKGROUND: Ultrasound is a critical non-invasive test for preoperative diagnosis of ovarian cancer. Deep learning is making advances in image-recognition tasks; therefore, we aimed to develop a deep convolutional neural network (DCNN) model that automates evaluation of ultrasound images and to facilitate a more accurate diagnosis of ovarian cancer than existing methods. METHODS: In this retrospective, multicentre, diagnostic study, we collected pelvic ultrasound images from ten hospitals across China between September 2003, and May 2019. We included consecutive adult patients (aged ≥18 years) with adnexal lesions in ultrasonography and healthy controls and excluded duplicated cases and patients without adnexa or pathological diagnosis. For DCNN model development, patients were assigned to the training dataset (34 488 images of 3755 patients with ovarian cancer, 541 442 images of 101 777 controls). For model validation, patients were assigned to the internal validation dataset (3031 images of 266 patients with ovarian cancer, 5385 images of 602 with benign adnexal lesions), external validation datasets 1 (486 images of 67 with ovarian cancer, 933 images of 268 with benign adnexal lesions), and 2 (1253 images of 166 with ovarian cancer, 5257 images of 723 benign adnexal lesions). Using these datasets, we assessed the diagnostic value of DCNN, compared DCNN with 35 radiologists, and explored whether DCNN could augment the diagnostic accuracy of six radiologists. Pathological diagnosis was the reference standard. FINDINGS: For DCNN to detect ovarian cancer, AUC was 0·911 (95% CI 0·886-0·936) in the internal dataset, 0·870 (95% CI 0·822-0·918) in external validation dataset 1, and 0·831 (95% CI 0·793-0·869) in external validation dataset 2. The DCNN model was more accurate than radiologists at detecting ovarian cancer in the internal dataset (88·8% vs 85·7%) and external validation dataset 1 (86·9% vs 81·1%). Accuracy and sensitivity of diagnosis increased more after DCNN-assisted diagnosis than assessment by radiologists alone (87·6% [85·0-90·2] vs 78·3% [72·1-84·5], p<0·0001; 82·7% [78·5-86·9] vs 70·4% [59·1-81·7], p<0·0001). The average accuracy of DCNN-assisted evaluations for six radiologists reached 0·876 and were significantly augmented when they were DCNN-assisted (p<0·05). INTERPRETATION: The performance of DCNN-enabled ultrasound exceeded the average diagnostic level of radiologists matched the level of expert ultrasound image readers, and augmented radiologists' accuracy. However, these observations warrant further investigations in prospective studies or randomised clinical trials. FUNDING: National Key Basic Research Program of China, National Sci-Tech Support Projects, and National Natural Science Foundation of China.

Dearomatization-rearomatization strategy of tyrosine for peptide/protein modification through thiol-addition reactions.

We have developed a dearomatization-rearomatization strategy for the modification of peptides/proteins through a thiol-Michael addition to the electrophilic cyclohexadienone intermediate that is generated in situ via the oxidation of tyrosine. This strategy enriches the conjugation toolbox and has great potential for applications in medicinal chemistry and chemical biology.

Detection of cell-surface sialic acids and photodynamic eradication of cancer cells using dye-modified polydopamine-coated gold nanobipyramids.

A nanoprobe based on polydopamine-coated gold nanobipyramids surface modified with molecules of a phenylboronic acid-substituted distyryl boron dipyrromethene has been fabricated and characterised using various physical and spectroscopic methods. It serves as an ultrasensitive sensor for sialic acids on the surface of cancer cells based on its dual surface-enhanced Raman scattering and fluorescence response. This biomarker can also trigger the photodynamic activity of these nanobipyramids, effectively eradicating the cancer cells mainly through apoptosis as shown by various bioassays.

Tyrosine-Specific Modification via a Dearomatization-Rearomatization Strategy: Access to Azobenzene Functionalized Peptides.

Azobenzene functionalized peptides are of great importance in photoresponsive biosystems and photopharmacology. Herein, we report an efficient approach to prepare azobenzene functionalized peptides through late-stage modification of tyrosine-containing peptides using a dearomatization-rearomatization strategy. This approach shows good chemoselectivity and site selectivity as well as sensitive group tolerance to various peptides. This method enriches the postsynthetic modification toolbox of peptides and has great potential to be applied in medicinal chemistry and chemical biology.