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Abstract We study the mass spectra and spin alignment of vector meson J/ψ in a thermal magnetized background using a generalized theoretical framework based on gauge/gravity duality. Utilizing a soft wall model for the QGP background and a massive vector field for the J/ψ meson, we delve into the meson’s spectral function and spin parameters (λ θ , λ φ , λ θφ ) for different cases, assessing their response to variations in magnetic field strength, momentum, and temperature. We initially examine scenarios where a meson’s momentum aligns parallel to the magnetic field in helicity frame. Our results reveal a magnetic field-induced positive λ θ H $$ {\lambda}_{\theta}^{\textrm{H}} $$ for low meson momentum, transitioning to negative with increased momentum. As a comparison, we also study the case of momentum perpendicular to the magnetic field and find the direction of magnetic field does not affect the qualitative behavior for the eB-dependence of λ θ H $$ {\lambda}_{\theta}^{\textrm{H}} $$ . Moreover, we apply our model to real heavy-ion collisions for three different spin quantization directions. Further comparisons with experimental data show qualitative agreement for spin parameters λ θ and λ φ in the helicity and Collins-Soper frames.

Abstract Purpose To develop and validate a nomogram based on 3D-PDU parameters and clinical characteristics to predict LNM and LVSI in early-stage cervical cancer preoperatively. Materials and methods A total of first diagnosis 138 patients with cervical cancer who had undergone 3D-PDU examination before radical hysterectomy plus lymph dissection between 2014 and 2019 were enrolled for this study. Multivariate logistic regression analyses were performed to analyze the 3D-PDU parameters and selected clinicopathologic features and develop a nomogram to predict the probability of LNM and LVSI in the early stage. ROC curve was used to evaluate model differentiation, calibration curve and Hosmer-Lemeshow test were used to evaluate calibration, and DCA was used to evaluate clinical practicability. Results Menopause status, FIGO stage and VI were independent predictors of LNM. BMI and maximum tumor diameter were independent predictors of LVSI. The predicted AUC of the LNM and LSVI models were 0.845 (95%CI,0.765–0.926) and 0.714 (95%CI,0.615–0.813). Calibration curve and H-L test (LNM groups P = 0.478; LVSI P = 0.783) all showed that the predicted value of the model had a good fit with the actual observed value, and DCA indicated that the model had a good clinical net benefit. Conclusion The proposed nomogram based on 3D-PDU parameters and clinical characteristics has been proposed to predict LNM and LVSI with high accuracy, demonstrating for the first time the potential of non-invasive prediction. The probability derived from this nomogram may have the potential to provide valuable guidance for physicians to develop clinical individualized treatment plans of FIGO patients with early cervical cancer.

Abstract This study aimed to investigate the effects of tea green leafhopper damage on the sensory quality and metabolite composition of Oriental Beauty by using tea leaves from different varieties of tea plants and processing factories. The results indicated that tea green leafhopper damage could reduce bitterness and increase the level of fruity aroma, which was related to the content changes of catechin components and alcohol substances. Furthermore, the tea green leafhopper salivary treatment experiment revealed that the decrease of catechin content and increase of theaflavin content were mainly influenced by the action of saliva and mechanical injury, and changes in volatile components such as linalool oxidation were responsible for the alteration in aroma. These findings provide a theoretical reference for the aroma formation and quality improvement of Oriental Beauty.

Objective Pine needles are rich in many nutrients and exhibit antibacterial and antioxidant biological activities; however, the effects of different production methods of pine needle additives on the growth performance and intestinal flora of broiler chickens are not known. Methods Normal diets were supplemented with pine needle fermentation juice (PNF), pine needle soaking juice (PNS), or pine needle powder (PNP), and the associated effects on growth performance, relative organ weights, intestinal development, intestinal histological morphology, intestinal flora, meat quality, and serum indicators in broiler chickens were observed. Results The results showed that PNF, PNS, and PNP all significantly improved feed utilisation and promoted the growth and development of broilers. All three additives also significantly improved the structure of the intestinal flora, specifically increasing the diversity of bacteria; increasing the abundance of beneficial bacteria, such as Faecalibacterium, Rikenella, and Blautia; and decreasing the abundance of harmful bacteria, such as Staphylococcus. The antioxidant properties of pine needles were also found to intensify lipid metabolic reactions in the blood, thus leading to lower triglycerides and total cholesterol. Meanwhile, high doses of PNF reduced jejunum and ileum weights and also increased meat yellowness. Lastly, none of PNF, PNS, or PNP had an effect on relative organ weights or intestinal histological morphology. Conclusion The addition of pine needles to the diet of broiler chickens can effectively promote their growth performance as well as improve their intestinal flora and serum status without side effects; in particular, the dose of 0.2% of either PNF and PNS is expected to have the capacity to replace growth-promoting antibiotics as diet additives.

Abstract We study the mass spectra of hidden-charm tetraquark systems with quantum numbers (I G )J P = (1+)1+ (and their I = 1 2 $$ \frac{1}{2} $$ partners) using QCD sum rules. The analysis incorporates the complete next-to-leading order (NLO) contribution to the perturbative QCD part of the operator product expansions, with particular attention to operator mixing effects due to renormalization group evolution. We find that both the parametric dependence and the perturbative convergence are significantly improved for the two mixed operators J 1 , 5 Mixed $$ {J}_{1,5}^{\textrm{Mixed}} $$ and J 2 , 6 Mixed $$ {J}_{2,6}^{\textrm{Mixed}} $$ , compared with those for the unmixed meson-meson or diquark-antidiquark type ones. For the d ¯ c c ¯ u $$ \overline{d}c\overline{c}u $$ system, the masses of J 1 , 5 Mixed $$ {J}_{1,5}^{\textrm{Mixed}} $$ and J 2 , 6 Mixed $$ {J}_{2,6}^{\textrm{Mixed}} $$ are determined to be 3.89 − 0.12 + 0.18 $$ {3.89}_{-0.12}^{+0.18} $$ GeV and 4.03 − 0.07 + 0.06 $$ {4.03}_{-0.07}^{+0.06} $$ GeV, respectively, closely matching those of Z c (3900) and Z c (4020). Similarly, for the s ¯ c c ¯ u $$ \overline{s}c\overline{c}u $$ states, the masses of J 1 , 5 Mixed $$ {J}_{1,5}^{\textrm{Mixed}} $$ and J 2 , 6 Mixed $$ {J}_{2,6}^{\textrm{Mixed}} $$ are found to be 4.02 − 0.09 + 0.17 $$ {4.02}_{-0.09}^{+0.17} $$ GeV and 4.21 − 0.07 + 0.08 $$ {4.21}_{-0.07}^{+0.08} $$ GeV, respectively, in close proximity to Z cs (3985)/Z cs (4000) and Z cs (4220), consistent with the expectation that they are the partners of Z c (3900) and Z c (4020). Our results highlight the crucial role of operator mixing, an inevitable effect in a complete NLO calculation, in achieving a robust phenomenological description for the tetraquark system.

Abstract Thermosensation is vital for the survival, propagation, and adaption of all organisms, but its mechanism is not fully understood yet. Here, we find that TMC6, a membrane protein of unknown function, is highly expressed in dorsal root ganglion (DRG) neurons and functions as a Gαq-coupled G protein-coupled receptor (GPCR)-like receptor to sense noxious heat. TMC6-deficient mice display a substantial impairment in noxious heat sensation while maintaining normal perception of cold, warmth, touch, and mechanical pain. Further studies show that TMC6 interacts with Gαq via its intracellular C-terminal region spanning Ser780 to Pro810. Specifically disrupting such interaction using polypeptide in DRG neurons, genetically ablating Gαq, or pharmacologically blocking Gαq-coupled GPCR signaling can replicate the phenotype of TMC6 deficient mice regarding noxious heat sensation. Noxious heat stimulation triggers intracellular calcium release from the endoplasmic reticulum (ER) of TMC6- but not control vector-transfected HEK293T cell, which can be significantly inhibited by blocking PLC or IP3R. Consistently, noxious heat-induced intracellular Ca2+ release from ER and action potentials of DRG neurons largely reduced when ablating TMC6 or blocking Gαq/PLC/IP3R signaling pathway as well. In summary, our findings indicate that TMC6 can directly function as a Gαq-coupled GPCR-like receptor sensing noxious heat.

Abstract Background The vaccination status of post-stroke patients, who are at high risk of severe outcomes from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a significant concern, yet it remains unclear. We aimed to explore the vaccination status, factors associated with vaccine hesitancy, and adverse effects after vaccination among post-stroke patients. Methods This multi-center observational study enrolled hospitalized post-stroke patients from six Chinese hospitals (Oct 1, 2020 - Mar 31, 2021), examining vaccine uptake and self-reported reasons for vaccine hesitancy, utilizing logistic regression to investigate risk factors for vaccine hesitancy, and recording any adverse reactions post-vaccination. Results Of the total 710 post-stroke patients included in the study, 430 (60.6%) had completed the recommended full-3 dose SARS-CoV-2 vaccination, with 176 (24.8%) remaining unvaccinated. The most common reasons for vaccine hesitancy were concerns about vaccine side effects (41.5%) and impaired mobility (33.9%). Logistic regression identified advanced age (aOR = 1.97, 95%CI: 1.36–2.85, P = 0.001), lower Barthel Index score (aOR = 0.88, 95%CI: 0.82–0.93, P = 0.018), higher Modified Rankin Scale score (aOR = 1.85, 95%CI: 1.32–2.56, P = 0.004), and poorer usual activity level of EuroQol 5-Dimension (aOR = 2.82, 95%CI: 1.51–5.28, P = 0.001) as independent risk factors for vaccine hesitancy. Approximately 14.8% reported minor adverse reactions, mainly pain at the injection site. Conclusion We found that post-stroke patients have insufficient SARS-CoV-2 vaccination rates, with key risk factors for vaccine hesitancy including concerns about side effects, advanced age, and functional impairments. No severe adverse reactions were observed among the vaccinated population.

Abstract Wavefront control is the fundamental requirement in optical informatics. Planar optics have drawn intensive attention due to the merits of compactness and light weight. However, it remains a challenge to freely manipulate the dispersion, hindering practical applications, especially in imaging. Here, we propose the concept of frequency-synthesized phase engineering to solve this problem. A phasefront-frequency matrix is properly designed to encode different spatial phases to separate frequencies, thus makes arbitrary dispersion tailoring and even frequency-separated functionalization possible. The periodically rotated director endows cholesteric liquid crystal with a spin and frequency selective reflection. Moreover, via presetting the local initial orientation of liquid crystal, geometric phase is encoded to the reflected light. We verify the proposed strategy by cascading the chiral anisotropic optical media of specifically designed helical pitches and initial director orientations. By this means, planar lenses with RGB achromatic, enhanced chromatic aberration and color routing properties are demonstrated. Inch-sized and high-efficient lenses are fabricated with low crosstalk among colors. It releases the freedom of dispersion control of planar optics, and even enables frequency decoupled phase modulations. This work brings new insights to functional planar optics and may upgrade the performance of existing optical apparatuses.

Abstract Background Peutz–Jeghers syndrome (PJS) is a rare genetic disorder characterized by the development of pigmented spots, gastrointestinal polyps and increased susceptibility to cancers. Currently, most studies have investigated intestinal microbiota through fecal microbiota, and there are few reports about mucosa-associated microbiota. It remains valuable to search for the key intestinal microbiota or abnormal metabolic pathways linked to PJS. Aim This study aimed to assess the structure and composition of mucosa-associated microbiota in patients with PJS and to explore the potential influence of intestinal microbiota disorders and metabolite changes on PJS. Methods The bacterial composition was analyzed in 13 PJS patients and 12 controls using 16S rRNA gene sequencing (Illumina MiSeq) for bacteria. Differential analyses of the intestinal microbiota were performed from the phylum to species level. Liquid chromatography-tandem mass spectrometry (LC‒MS) was used to detect the differentially abundant metabolites of PJS patients and controls to identify different metabolites and metabolic biomarkers of small intestinal mucosa samples. Results High-throughput sequencing confirmed the special characteristics and biodiversity of the mucosa microflora in patients with PJS. They had lower bacterial biodiversity than controls. The abundance of intestinal mucosal microflora was significantly lower than that of fecal microflora. In addition, lipid metabolism, amino acid metabolism, carbohydrate metabolism, nucleotide metabolism and other pathways were significantly different from those of controls, which were associated with the development of the enteric nervous system, intestinal inflammation and development of tumors. Conclusion This is the first report on the mucosa-associated microbiota and metabolite profile of subjects with PJS, which may be meaningful to provide a structural basis for further research on intestinal microecology in PJS.

Abstract Helicobacter pylori (H. pylori), known for causing gastric inflammation, gastritis and gastric cancer, prompted our study to investigate the differential expression of cytokines in gastric tissues, which is crucial for understanding H. pylori infection and its potential progression to gastric cancer. Focusing on Il-1β, IL-6, IL-8, IL-12, IL-18, and TNF-α, we analysed gene and protein levels to differentiate between H. pylori-infected and non-infected gastritis. We utilised real-time quantitative polymerase chain reaction (RT-qPCR) for gene quantification, immunohistochemical staining, and ELISA for protein measurement. Gastric samples from patients with gastritis were divided into three groups: (1) non-gastritis (N-group) group, (2) gastritis without H. pylori infection (G-group), and (3) gastritis with H. pylori infection (GH-group), each consisting of 8 samples. Our findings revealed a statistically significant variation in cytokine expression. Generally, cytokine levels were higher in gastritis, but in H. pylori-infected gastritis, IL-1β, IL-6, and IL-8 levels were lower compared to H. pylori-independent gastritis, while IL-12, IL-18, and TNF-α levels were higher. This distinct cytokine expression pattern in H. pylori-infected gastritis underscores a unique inflammatory response, providing deeper insights into its pathogenesis.

BackgroundVasculogenic Mimicry (VM) can reduce the efficacy of anti-angiogenesis and promote distant metastasis in hepatocellular carcinoma (HCC). Our previous studies have found that Celastrus orbiculatus extract (COE) can inhibit the VM formation in HCC by reducing EphA2 expression. However the underlying mechanism related to EphA2 in VM formation is unclear.PurposeThis study aimed to confirm that EphA2 is one of the potential targets of COE, and to explore the effect of EphA2 in VM formation in hypoxia context in HCC.MethodsTCM Systems Pharmacology database and proteomics analysis were used to explore the key targets of COE in HCC treatment. CD31-PAS double staining and VE-CAD staining were used to indicate vasculogenic mimicry. The localization of EphA2 and VE-CAD was examined through fluorescent microscopy. CCK8 assay, cell invasion assay, and tube formation assay were used to indicate the formation of VM under hypoxic conditions. The regulatory relationship of EphA2 upstream and downstream molecules were evaluated through COIP and Western Blot. The nude mouse xenograft tumor models were used to observe the VM formation after knocking down or overexpressing EphA2.ResultsEphA2 is identified to the target of COE, and the driving gene of HCC. In HCC surgical specimens, EphA2 expression is closely associated with the VM formation of HCC. COE-regulated EphA2 is involved in hypoxia-induced VM formation in HCC cells in vitro. EphA2 is regulated by HIF directly or indirectly by C-MYC. Overexpression of EphA2 can promote the VM formation of HCC in nude mice, while knocking down EphA2 can inhibit the VM formation.ConclusionEphA2, as a target of COE, plays a crucial regulatory role in the formation of vasculogenic mimicry in HCC, involving upstream HIF/MYC transcriptional promotion and downstream PI3K/FAK/VE-CAD expression regulation.

Background: The current prophylactic tuberculosis vaccine Bacille Calmette-Guérin (BCG), was derived in the 1920s, but the humoral immune responses induced by BCG vaccination have not been fully elucidated to date. In this study, our aim was to reveal the profiles of antibody responses induced by BCG vaccination in adults and identify the potential biomarkers for evaluating the BCG vaccination response. Methods: Proteome microarrays were performed to reveal the serum profiles of antibody responses induced by BCG vaccination in adults. ELISA was used to validate the potential biomarkers in validation cohort (79 healthy controls and 58 BCG-vaccinated subjects). Then combined panel was established by logistic regression analysis based on OD values of potential biomarkers. Results: Multiple antigens elicited stronger serum IgG or IgM antibody responses in BCG vaccinated subjects than healthy subjects at 12 weeks post BCG vaccination; among the antigens, Rv0060, Rv2026c and Rv3379c were further verified using 137 serum samples and presented the moderate performance in assessment of the BCG vaccination response by receiver operating characteristic analysis. Furthermore, a combined panel exhibited an improved AUC of 0.923, and the sensitivity and specificity were 77.59 % and 91.14 %, respectively. In addition, the antibody response against Rv0060, Rv2026c and Rv3379c was related to the clinical background to a certain extent. Conclusions: The novel antigens identified in our study could offer better knowledge towards developing a more efficacious vaccine based on humoral immune responses, and they could be potential biomarkers in assessments of BCG vaccination responses.

An electron vortex beam (EVB) carrying orbital angular momentum (OAM) plays a key role in a series of fundamental scientific researches, such as chiral energy-loss spectroscopy and magnetic dichroism spectroscopy. So far, almost all the experimentally created EVBs manifest isotropic doughnut intensity patterns. Here, based on the correlation between local divergence angle of electron beam and phase gradient along azimuthal direction, we show that free electrons can be tailored to EVBs with customizable intensity patterns independent of the carried OAM. As proof-of-concept, by using computer generated hologram and designing phase masks to shape the incident free electrons in the transmission electron microscope, three structured EVBs carrying identical OAM are tailored to exhibit completely different intensity patterns. Furthermore, through the modal decomposition, we quantitatively investigate their OAM spectral distributions and reveal that structured EVBs present a superposition of a series of different eigenstates induced by the locally varied geometries. These results not only generalize the concept of EVB, but also demonstrate an extra highly controllable degree of freedom for electron beam manipulation in addition to OAM.

Abstract We perform a high-precision computation of the three-loop three-point form factor of the stress-tensor supermultiplet in N $$ \mathcal{N} $$ = 4 SYM. Both the leading-color and sub-leading-color form factors are expanded in terms of simple integrals. We compute the complete set of integrals at a special kinematic point with very high precision using AMFlow. The high-precision leading-color result enables us to obtain the analytic form of a numerical constant in the three-loop BDS ansatz, which is previously known only numerically. The high-precision values of the non-leading-color finite remainder as well as all integrals are also presented, which can be valuable for future use.

Abstract Background Computed tomography (CT) plays a great role in characterizing and quantifying changes in lung structure and function of chronic obstructive pulmonary disease (COPD). This study aimed to explore the performance of CT-based whole lung radiomic in discriminating COPD patients and non-COPD patients. Methods This retrospective study was performed on 2785 patients who underwent pulmonary function examination in 5 hospitals and were divided into non-COPD group and COPD group. The radiomic features of the whole lung volume were extracted. Least absolute shrinkage and selection operator (LASSO) logistic regression was applied for feature selection and radiomic signature construction. A radiomic nomogram was established by combining the radiomic score and clinical factors. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were used to evaluate the predictive performance of the radiomic nomogram in the training, internal validation, and independent external validation cohorts. Results Eighteen radiomic features were collected from the whole lung volume to construct a radiomic model. The area under the curve (AUC) of the radiomic model in the training, internal, and independent external validation cohorts were 0.888 [95% confidence interval (CI) 0.869–0.906], 0.874 (95%CI 0.844–0.904) and 0.846 (95%CI 0.822–0.870), respectively. All were higher than the clinical model (AUC were 0.732, 0.714, and 0.777, respectively, P

Abstract The next generation of high-capacity, multi-task optical informatics requires sophisticated manipulation of multiple degrees of freedom (DoFs) of light, especially when they are coupled in a non-separable way. Vector beam, as a typical non-separable state between the spin and orbital angular momentum DoFs, mathematically akin to entangled qubits, has inspired multifarious theories and applications in both quantum and classical regimes. Although qubit rotation is a vital and ubiquitous operation in quantum informatics, its classical analogue is rarely studied. Here, we demonstrate the logical rotation of vectorial non-separable states via the uniform self-assembled chiral superstructures, with favorable controllability, high compactness and exemption from formidable alignment. Photonic band engineering of such 1D chiral photonic crystal renders the incident-angle-dependent evolution of the spatially-variant polarizations. The logical rotation angle of a non-separable state can be tuned in a wide range over 4π by this single homogeneous device, flexibly providing a set of distinguished logic gates. Potential applications, including angular motion tracking and proof-of-principle logic network, are demonstrated by specific configuration. This work brings important insight into soft matter photonics and present an elegant strategy to harness high-dimensional photonic states.

Abstract For classical waves, phase matching is vital for enabling efficient energy transfer in many scenarios, such as waveguide coupling and nonlinear optical frequency conversion. Here, we propose a temporal quasi-phase matching method and realize robust and complete acoustical energy transfer between arbitrarily detuned cavities. In a set of three cavities, A, B, and C, the time-varying coupling is established between adjacent elements. Analogy to the concept of stimulated Raman adiabatic passage, amplitudes of the two couplings are modulated as time-delayed Gaussian functions, and the couplings’ signs are periodically flipped to eliminate temporal phase mismatching. As a result, robust and complete acoustic energy transfer from A to C is achieved. The non-reciprocal frequency conversion properties of our design are demonstrated. Our research takes a pivotal step towards expanding wave steering through time-dependent modulations and is promising to extend the frequency conversion based on state evolution in various linear Hermitian systems to nonlinear and non-Hermitian regimes.

Abstract Endowing flexible and adaptable fiber devices with light-emitting capabilities has the potential to revolutionize the current design philosophy of intelligent, wearable interactive devices. However, significant challenges remain in developing fiber devices when it comes to achieving uniform and customizable light effects while utilizing lightweight hardware. Here, we introduce a mass-produced, wearable, and interactive photochromic fiber that provides uniform multicolored light control. We designed independent waveguides inside the fiber to maintain total internal reflection of light as it traverses the fiber. The impact of excessive light leakage on the overall illuminance can be reduced by utilizing the saturable absorption effect of fluorescent materials to ensure light emission uniformity along the transmission direction. In addition, we coupled various fluorescent composite materials inside the fiber to achieve artificially controllable spectral radiation of multiple color systems in a single fiber. We prepared fibers on mass-produced kilometer-long using the thermal drawing method. The fibers can be directly integrated into daily wearable devices or clothing in various patterns and combined with other signal input components to control and display patterns as needed. This work provides a new perspective and inspiration to the existing field of fiber display interaction, paving the way for future human–machine integration.

Abstract Branched flows occur ubiquitously in various wave systems, when the propagating waves encounter weak correlated scattering potentials. Here we report the experimental realization of electrical tuning of the branched flow of light using a nematic liquid crystal (NLC) system. We create the physical realization of the weakly correlated disordered potentials of light via the inhomogeneous orientations of the NLC. We demonstrate that the branched flow of light can be switched on and off as well as tuned continuously through the electro-optical properties of NLC film. We further show that the branched flow can be manipulated by the polarization of the incident light due to the optical anisotropy of the NLC film. The nature of the branched flow of light is revealed via the unconventional intensity statistics and the rapid fidelity decay along the light propagation. Our study unveils an excellent platform for the tuning of the branched flow of light which creates a testbed for fundamental physics and offers a new way for steering light.

Bound states in the continuum (BICs) with exceptionally high quality factors ($Q$ factors) have become focal points in photonic device research, finding applications in nonlinear enhancement, laser generation, sensing, and beyond. In this study, we systematically investigate the intricate relationship between the in-plane symmetry groups of photonic crystals and symmetry-protected BICs (SP-BICs) using a rigorous group theory approach. By modifying the spatial distribution of refractive indices to perturb the $C_{2}$ and $C_{3}$ symmetries within a $C_{6v}$ photonic crystal slab, we introduce a novel method to enable precise tuning of BIC resonances, including the BIC frequency, $Q$ factor, and polarization state. The proposed group theory approach and tuning mechanism establish a pioneering pathway for the design and tunability of BICs, opening avenues for the development of advanced photonic devices with tailored functionalities such as tunable lasers and optical sensors with enhanced performance.

Abstract Liquid crystals are a vital component of modern photonics, and recent studies have demonstrated the exceptional sensing properties of stimuli-responsive cholesteric liquid crystals. However, existing cholesteric liquid crystal-based sensors often rely on the naked eye perceptibility of structural color or the measurement of wavelength changes by spectrometric tools, which limits their practical applications. Therefore, developing a platform that produces recognizable sensing signals is critical. In this study, we present a visual sensing platform based on geometric phase encoding of stimuli-responsive cholesteric liquid crystal polymers that generates real-time visual patterns, rather than frequency changes. To demonstrate this platform’s effectiveness, we used a humidity-responsive cholesteric liquid crystal polymer film encoded with a q-plate pattern, which revealed that humidity causes a shape change in the vortex beam reflected from the encoded cholesteric liquid crystal polymers. Moreover, we developed a prototype platform towards remote humidity monitoring benefiting from the high directionality and long-range transmission properties of laser beams carrying orbital angular momentum. Our approach provides a novel sensing platform for cholesteric liquid crystals-based sensors that offers promising practical applications. The ability to generate recognizable sensing signals through visual patterns offers a new level of practicality in the sensing field with stimuli-responsive cholesteric liquid crystals. This platform might have significant implications for a broad readership and will be of interest to researchers working in the field of photonics and sensing technology.

Abstract The iron oxide nanoparticles (IONPs), possessing both magnetic behavior and semiconductor property, have been extensively used in multifunctional biomedical fields due to their biocompatible, biodegradable and low toxicity, such as anticancer, antibacterial, cell labelling activities. Nevertheless, there are few IONPs in clinical use at present. Some IONPs approved for clinical use have been withdrawn due to insufficient understanding of its biomedical applications. Therefore, a systematic summary of IONPs’ preparation and biomedical applications is crucial for the next step of entering clinical practice from experimental stage. This review summarized the existing research in the past decade on the biological interaction of IONPs with animal/cells models, and their clinical applications in human. This review aims to provide cutting-edge knowledge involved with IONPs’ biological effects in vivo and in vitro, and improve their smarter design and application in biomedical research and clinic trials. Graphical Abstract

Objective To preliminarily summarize the epidemiological and clinical characteristics of functional movement disorder (FMD) based on movement disorders clinic in China. Methods and Results A total of 593 patients with movement disorders newly diagnosed in movement disorders clinic of 22 clinical medical centers from August to September in 2023 were included, including 37 patients (6.24%) with FMD and 556 patients (93.76%) with organic movement disorder. Comparison of the epidemiological characteristics of the 2 groups, the proportions of corona virus disease (COVID⁃19) infection (χ2 = 4.217, P = 0.040) and psychopsychological symptoms (χ2 = 18.694, P = 0.000) in the FMD group were higher than those in the organic movement disorder group, while age (t = 3.757, P = 0.000), age of onset (t = 3.720, P = 0.000) and proportion of hypertension (χ2 = 4.736, P = 0.030) were lower than those in the organic movement disorder group. Comparison of the clinical characteristics of the 2 groups, the FMD group had higher proportions of tremor (χ2 = 3.955, P = 0.047) and myoclonus (Fisher′s exact probability: P = 0.011) than the organic movement disorder group, and the proportions of parkinsonism (χ2 = 8.491, P = 0.004) and gait disorder (χ2 = 5.028, P = 0.025) were lower than those in the organic movement disorder group. Conclusions The age and age of onset, as well as the proportions of COVID⁃19 infection, hypertension, psychopsychological symptoms, tremor, myoclonus, parkinsonism and gait disorder with FMD were different from those with organic movement disorder in China.

Inflammatory bowel disease (IBD) is a systemic disorder affecting intestinal tract and other organs outside the gut, known as extraintestinal manifestations (EIMs). These EIMs are complex and diverse, and early treatment may reduce teratogenic rates and improve quality of life. However, our understanding of EIMs in IBD is currently limited by a lack of mechanistic insight. Fortunately, advances in our understanding of intestinal microecology are allowing us to uncover the underlying mechanisms of EIMs. The gut microbiota can drive aberrant immune activation and intestinal inflammation. Intriguingly, chronic inflammation can also shape the microbiome in reverse and aggravate dysbiosis. Recent research has revealed that microbiome-derived signal molecules play a crucial role in catalyzing enterocolitis and altering mucosal barrier function. Furthermore, gut microbiota-associated antigens can translocate from the intestine to extraintestinal sites, leading to systemic inflammatory responses. The microbiome is showing its potential in treating IBD and EIMs, and microbial engineering approaches, such as probiotic engineering and engineered fecal microbiota transplantation, are exhibiting great promise for IBD therapeutics.

ObjectiveTo investigate the clinical characteristics and risk factors of patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases.MethodsA retrospective analysis of general clinical data was conducted on patients with SARS-CoV-2 omicron infection complicated with hypertension, coronary heart disease, and heart failure admitted to one hospital in Guangdong Province from December 1, 2022, to February 28, 2023. Clinical symptoms, laboratory tests, imaging examinations, treatment, and clinical outcomes were collected. Multivariate logistic regression analysis was used to analyze the risk factors for mortality in patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases. ROC curves were drawn to evaluate the predictive value of CRP, D-dimer, and CK-MB in predicting the risk of death.ResultsA total of 364 confirmed cases were included, divided into the asymptomatic group, mild to moderate group, and severe to critically ill group based on the symptoms of COVID-19. There were 216 males (59.34%) and 148 females (40.66%), with a median age of 75 years. The differences between the three groups in terms of sex and age were statistically significant (p

Fast motion and high adaptability are crucial for the practical applications of miniature robots. However, combining these capabilities into a single robot skillfully is challenging, particularly in the domain of miniature structural design. Inspired by the amphibious motion of crocodiles in nature, a hollow piezoelectric miniature robot (HPMR) is proposed. The key benefit of the HPMR is to concurrently output the oscillating motion of the driving foot (oscillating mode) and the rotating motion of the internal rotor (rotating mode). That is, the mode of single‐energy‐input‐multimotion output allows the robot to balance the requirements of speed and adaptability. In the oscillating mode, HPMR can run at speeds of up to 12.3 BL s−1 and realize a displacement resolution of 0.3 μm. Following the conical rotor assembly, the rotor can operate at a speed of 890 rpm, with a displacement resolution of 7.28 mrad. In the rotating mode, the robot demonstrates its multitasking ability in moving amphibiously, carrying loads, running on surfaces with varying roughness, crossing obstacles, and resisting shocks. The results show that the HPMR is capable of fast, high‐resolution moving combined with high adaptability, opening up the possibility of using it for mobile detection tasks in real‐world settings.

Abstract Background Single-cell RNA sequencing (scRNA-seq) measurements of gene expression show great promise for studying the cellular heterogeneity of rice roots. How precisely annotating cell identity is a major unresolved problem in plant scRNA-seq analysis due to the inherent high dimensionality and sparsity. Results To address this challenge, we present NRTPredictor, an ensemble-learning system, to predict rice root cell stage and mine biomarkers through complete model interpretability. The performance of NRTPredictor was evaluated using a test dataset, with 98.01% accuracy and 95.45% recall. With the power of interpretability provided by NRTPredictor, our model recognizes 110 marker genes partially involved in phenylpropanoid biosynthesis. Expression patterns of rice root could be mapped by the above-mentioned candidate genes, showing the superiority of NRTPredictor. Integrated analysis of scRNA and bulk RNA-seq data revealed aberrant expression of Epidermis cell subpopulations in flooding, Pi, and salt stresses. Conclusion Taken together, our results demonstrate that NRTPredictor is a useful tool for automated prediction of rice root cell stage and provides a valuable resource for deciphering the rice root cellular heterogeneity and the molecular mechanisms of flooding, Pi, and salt stresses. Based on the proposed model, a free webserver has been established, which is available at https://www.cgris.net/nrtp .

Abstract We study the dissociation effect of $$J/\Psi $$ J / Ψ in magnetized, rotating QGP matter at finite temperature and chemical potential using gauge/gravity duality. By incorporating angular velocity into the holographic magnetic catalysis model, we analyze the influence of temperature, chemical potential, magnetic field, and angular velocity on the properties of $$J/\Psi $$ J / Ψ meson. The results reveal that temperature, chemical potential, and rotation enhance the dissociation effect and increase the effective mass in the QGP phase. However, the magnetic field suppresses dissociation, and its effect on the effective mass is non-trivial. Additionally, we explore the interplay between magnetic field and rotation, identifying a critical angular velocity that determines the dominant effect. As a parallel study, we also examine the rotation effect in the holographic inverse magnetic catalysis model, although the magnetic field exhibits distinctly different behaviors in these two models, the impact of rotation on the dissociation effect of $$J/\Psi $$ J / Ψ is similar. Finally, we investigate the influence of electric field and demonstrate that it also speeds up the $$J/\Psi $$ J / Ψ dissociation.

The study of high-energy and low-vulnerability propellants is important for the power performance and safety of solid propellant rocket motors. The modified split Hopkinson pressure bar (SHPB) tests are performed on two kinds of propellant with different crosslinking density to study the dynamic mechanical responses and damage-ignition mechanism. SHPB apparatus is equipped with a high-performance infrared camera and high-speed camera to capture the deformation, damage-ignition feature and temperature evolution images in the impact process. The results suggested that the mechanical responses and damage-ignition mechanism of the propellants were affected by the strain rates and crosslinking density. The damage-ignition degree is more intense and the reaction occurs earlier with the increase of strain rates. For propellant 1 with higher crosslinking density, the critical ignition strain rate is 4500 s−1. Two kinds of propellants show different ignition mechanism, i.e. crack generation, propagation and final fracture for propellant 1 while viscous shear flow for propellant 2. Meanwhile, the SEM images also reveal the difference of damage-ignition mechanism of the two kinds of propellants. Finally, the ignition mechanism under different strain rates and critical ignition strain rate of propellants are further explained by the theoretical calculation of temperature variations.

Abstract Astrocytes contribute to chronic neuroinflammation in a variety of neurodegenerative diseases, including Parkinson's disease (PD), the most common movement disorder. However, the precise role of astrocytes in neuroinflammation remains incompletely understood. Herein, we show that regulator of G-protein signaling 5 (RGS5) promotes neurodegenerative process through augmenting astrocytic tumor necrosis factor receptor (TNFR) signaling. We found that selective ablation of Rgs5 in astrocytes caused an inhibition in the production of cytokines resulting in mitigated neuroinflammatory response and neuronal survival in animal models of PD, whereas overexpression of Rgs5 had the opposite effects. Mechanistically, RGS5 switched astrocytes from neuroprotective to pro-inflammatory property via binding to the receptor TNFR2. RGS5 also augmented TNFR signaling-mediated pro-inflammatory response by interacting with the receptor TNFR1. Moreover, interrupting RGS5/TNFR interaction by either RGS5 aa 1–108 or small molecular compounds feshurin and butein, suppressed astrocytic cytokine production. We showed that the transcription of astrocytic RGS5 was controlled by transcription factor early B cell factor 1 whose expression was reciprocally influenced by RGS5-modulated TNF signaling. Thus, our study indicates that beyond its traditional role in G-protein coupled receptor signaling, astrocytic RGS5 is a key modulator of TNF signaling circuit with resultant activation of astrocytes thereby contributing to chronic neuroinflammation. Blockade of the astrocytic RGS5/TNFR interaction is a potential therapeutic strategy for neuroinflammation-associated neurodegenerative diseases.

Abstract Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an RNA-binding protein, is associated with tumorigenesis and progression. However, the exact molecular mechanisms of IGF2BP3 in colorectal cancer (CRC) oncogenesis, progression, and drug resistance remain unclear. This study found that IGF2BP3 was upregulated in CRC tissues. Clinically, the elevated IGF2BP3 level is predictive of a poor prognosis. Functionally, IGF2BP3 enhances CRC tumorigenesis and progression both in vitro and in vivo. Mechanistically, IGF2BP3 promotes epidermal growth factor receptor (EGFR) mRNA stability and translation and further activates the EGFR pathway by serving as a reader in an N6-methyladenosine (m6A)-dependent manner by cooperating with METTL14. Furthermore, IGF2BP3 increases the drug resistance of CRC cells to the EGFR-targeted antibody cetuximab. Taken together, our results demonstrated that IGF2BP3 was a functional and clinical oncogene of CRC. Targeting IGF2BP3 and m6A modification may therefore offer rational therapeutic targets for patients with CRC.

Nanostructured bismuth oxide bromide (BiOBr) has attracted considerable attention as a visible light catalyst. However, its photocatalytic degradation efficiency is limited by its low specific surface area. In this study, a solvothermal approach was employed to synthesize BiOBr, which was subsequently loaded onto cellulose nanofibers (CNFs) to obtain a bismuth halide composite catalyst. The performance of this catalyst in the removal of refractory organic pollutants such as tetracycline (TC) from solutions under visible light excitation was examined. Our results indicate that BiOBr/CNF effectively removes TC from the solution under light conditions. At a catalyst dosage of 100 mg/L, the removal efficiency for TC (with an initial concentration of 100 mg/L) was 94.2%. This study elucidates the relationship between the microstructure of BiOBr/CNF composite catalysts and their improved photocatalytic activity, offering a new method for effectively removing pollutants from water.

This paper proposes a deep learning (DL)-assisted high-pass-filter (HPF)-based fixed-threshold decision (FTD) for free-space optical (FSO) communication. HPF is applied to reduce the scintillation effect by filtering out the low-frequency components of the received signal. However, the performance is limited owing to the signal distortion from HPF and remnant scintillation effect due to insufficient filtering. Therefore, the DL model is adopted to improve the performance of HPF-based scintillation effect compensation. The multilayer perceptron (MLP) model is used to adaptively select the peak frequency component of the received signal as the optimized cutoff frequency of HPF. Furthermore, recurrent neural network (RNN) and long short-term memory (LSTM) models are cascaded after HPF to compensate for the remnant scintillation effect and recover the signal distortion without the optimization of HPF cutoff frequency. The simulation was conducted under different turbulence channels and data rates. Simulation results showed that MLP-assisted adaptive optimized cutoff frequency and cascaded LSTM and HPF methods were close to the adaptive-threshold decision with precise channel state information under various turbulence channel degrees.

Objectives: The prevalence of G6PD deficiency has not been reported in Yangjiang, a western city in Guangdong province. This study aims to investigate the molecular characteristics of G6PD deficiency in this region.Methods: Blood samples were collected from adults at a local hospital to screen for G6PD deficiency. The deficient samples were subjected to further analysis using PCR and reverse dot blot to determine the specific G6PD variants.Results: Among the 3314 male subjects, 250 cases of G6PD deficiency were found using the G6PD enzyme quantitative assay, resulting in a prevalence of 7.54% (250/3314) in the Yangjiang region. The prevalence of G6PD deficiency in females was 3.42% (176/5145). Out of the 268 cases of G6PD deficiency tested for G6PD mutations, reverse dot blot identified 20 different G6PD variants. The most common G6PD variant was c.1388G>A (81/268), followed by c.1376G>T (48/268), c.95A>G (32/268), c.1024C>T (9/268), c.392G>T (7/268), and c.871G>A/c.1311C>T (6/268). It was observed that c.871G>A was always linked to the polymorphism of c.1311C>T in this population.Conclusion: This investigation into G6PD deficiency in this area is expected to significantly improve our understanding of the prevalence and molecular characterization of this condition.

To better understand the effects of strong coupling and QCD at high temperature in QGP, by using holographic model, we investigate the dissociation effect of bottomonium under the higher-order curvature corrections to the supergravity action corresponding to the corrections of large N expansion of boundary CFT in the side of field theory. The results show that effective potential is not a good physical quantity to estimate the dissociation strength of bottomonium in the case of finite wave number and considering the higher-order curvature corrections. Therefore, we calculate the quasinormal spectra (QNMs) and the differential configuration entropy (DCE). It is found that the dissociation effect is stronger for the stronger coupling.

Sparganosis is a rare parasitic infection caused by plerocercoid tapeworm larvae. We described a case of a 27-year-old man presenting with numbness in both legs and masses in the right lung and spine, initially thought to have spinal metastasis from lung cancer. However, after pathological and parasitological examinations, the patient was found to have spinal sparganosis, likely due to a history of consuming raw frogs. The patient was successfully treated with praziquantel, resulting in the recovery of muscle strength in his legs. This case highlights the importance of considering spinal sparganosis as a differential diagnosis in patients with spinal masses, especially those with a history of consuming raw or undercooked frogs. Accurate diagnosis and early treatment are crucial for managing this infection.

Abstract Background IgA vasculitis nephritis (IgAVN) and IgA nephropathy (IgAN) share several clinical and pathological characteristics, though distinctions also exist. Their interrelation, however, remains undefined. This study investigates the clinicopathological divergences and prognostic disparities in pediatric patients with IgAVN and IgAN. Methods Our study encompasses 809 pediatric patients with IgAVN and 236 with IgAN, all of whom underwent kidney biopsy. We utilized the Semiquantitative Classification (SQC) scoring system to juxtapose the pathologies of the two conditions, and performed a COX regression analysis to examine factors influencing their prognoses. Results Both patient groups demonstrated a predominance of males. A seasonality was observed, with a higher incidence of IgAN in the summer, and IgAVN in the fall (P

Abstract Objectives Microcephaly is caused by reduced brain volume and most usually associated with a variety of neurodevelopmental disorders (NDDs). To provide an overview of the diagnostic yield of whole exome sequencing (WES) and promote novel candidates in genetically unsolved families, we studied the clinical and genetic landscape of an unselected Chinese cohort of patients with microcephaly. Methods We performed WES in an unselected cohort of 103 NDDs patients with microcephaly as one of the features. Full evaluation of potential novel candidate genes was applied in genetically undiagnosed families. Functional validations of selected variants were conducted in cultured cells. To augment the discovery of novel candidates, we queried our genomic sequencing data repository for additional likely disease-causing variants in the identified candidate genes. Results In 65 families (63.1%), causative sequence variants (SVs) and clinically relevant copy number variants (CNVs) with a pathogenic or likely pathogenic (P/LP) level were identified. By incorporating coverage analysis to WES, a pathogenic or likely pathogenic CNV was detected in 15 families (16/103, 15.5%). In another eight families (8/103, 7.8%), we identified variants in newly reported gene (CCND2) and potential novel neurodevelopmental disorders /microcephaly candidate genes, which involved in cell cycle and division (PWP2, CCND2), CDC42/RAC signaling related actin cytoskeletal organization (DOCK9, RHOF), neurogenesis (ELAVL3, PPP1R9B, KCNH3) and transcription regulation (IRF2BP1). By looking into our data repository of 5066 families with NDDs, we identified additional two cases with variants in DOCK9 and PPP1R9B, respectively. Conclusion Our results expand the morbid genome of monogenic neurodevelopmental disorders and support the adoption of WES as a first-tier test for individuals with microcephaly.

Abstract Objective and design An accumulating body of evidence has shown that gut microbiota is involved in regulating inflammation; however, it remains undetermined if and how gut microbiota plays an important role in modulating deep venous thrombosis (DVT), which is an inflammation-involved thrombotic event. Subjects Mice under different treatments were used in this study. Methods and treatment We induced stenosis DVT in mice by partially ligating the inferior vena cava. Mice were treated with antibiotics, prebiotics, probiotics, or inflammatory reagents to modulate inflammatory states, and their effects on the levels of circulating LPS and DVT were examined. Results Antibiotic-treated mice or germ-free mice exhibited compromised DVT. Treatment of mice with either prebiotics or probiotics effectively suppressed DVT, which was accompanied with the downregulation of circulating LPS. Restoration of circulating LPS in these mice with a low dose of LPS was able to restore DVT. LPS-induced DVT was blocked by a TLR4 antagonist. By performing proteomic analysis, we identified TSP1 as one of the downstream effectors of circulating LPS in DVT. Conclusion These results suggest that gut microbiota may play a nonnegligible role in modulating DVT by leveraging the levels of LPS in circulation, thus shedding light on the development of gut microbiota-based strategies for preventing and treating DVT.

C20H22Cu3N8O10, monoclinic, C2/c (no. 15), a = 12.0766(11) Å, b = 16.2778(14) Å, c = 14.7605(13) Å, β = 97.8580(10)∘, V = 2874.4(4) Å3, Z = 4, R gt(F) = 0.0420, wR ref (F 2) = 0.0988, T = 298.15 K.

At present, casein can be isolated from skim milk by membrane filtration technology, and micellar casein concentrate could be obtained by concentration, sterilization, drying. In this paper, the factors affecting the composition of micellar casein concentrate and its application in cheese production were reviewed. It was found that pH value, temperature and diafiltrant during membrane filtration all affected the composition of micellar casein concentrate, resulting in different concentrations of casein, whey protein, lactose and calcium. It is also possible to standardize raw milk by micellar casein concentrate to produce cheese with the same composition and quality. It is also possible to obtain different raw milk compositions by micellar casein concentrate having different components to produce cheese with desired quality and function. In conclusion, the addition of micellar casein concentrate could affect the composition, texture and flavor of cheese during cheese production, but these problems could be solved by adjusting the process parameters of membrane filtration and cheesemaking. Further research will be still required to find an economic way to preserve micellar casein concentrate and give it extended shelf life, good rennet properties to ensure cheese quality and yield.

Abstract The motional consensus of self-propelled particles is studied in both noise-free cases and cases with noise by the standard Vicsek model. In the absence of noise, we propose a simple method, using grid-based technique and defining the normalized variance of the ratio of the number of particles locally to globally, to quantitatively study the movement pattern of the system by the spatial distribution of the particles and the degree of aggregation of particles. It is found that the weaker correlation of velocity leads to larger degree of aggregation of the particles. In the cases with noise, we quantify the competition between velocity alignment and noise by considering the difference of the variety of order parameter result from the velocity alignment and noise. The variation of the effect of noise on motional consensus is non-monotonic for the change of the probability distribution of noise from uniform to non-uniform. Our results may be useful and encourage further efforts in exploring the basic principles of collective motion.

The human eye has various axes and angles, of which the angle Kappa is an important indicator of the centrality of the human eye and is widely used in ophthalmic surgery. Proper preoperative evaluation and application of the angle Kappa facilitated the achievement of optimal postoperative visual quality. Chord mu is a new term that has emerged recently to better express the angle Kappa. The two concepts are not well understood clinically, limiting their usefulness. Therefore, to better understand the angle Kappa and chord mu, the definitions and connections between them are presented separately in this paper. Meanwhile, the application of angle Kappa in strabismus surgery was summarized, the method for compensating large angle Kappa in corneal refractive surgery and the clinical significance of angle Kappa in predicting postoperative centrality of multifocal intraocular lens(MIOL)in phacoemulsification combined with MIOL implantation were discussed, with a view to providing references for clinical work.

To study the effect of interface behaviour on the mechanical properties and damage evolution of PBX under combined tension–shear loading, the present work establishes the numerical model of a PBX three-phase hybrid system, which introduces a nonlinear plastic damage cohesion model to study the mechanical response and damage process. The parameters in the model were fitted and calibrated. Taking the crack growth rate as the feature, the damage state in each stage was determined, and the damage instability criterion was given. The effects of interfacial tensile strength and shear strength on the damage process of PBX were studied. On this basis, serrated and hemispherical structures interface of PBX has been developed, which affects the damage process and instability during the loading process. The results indicate that damage state response of PBX experiences the process of stable load bearing, unstable propagation, and complete failure. At the critical moment of instability, the overall equivalent effective strain of material reaches 3024 με and instability loading displacement reaches 0.39 mm. The increase of interfacial tensile strength and shear strength significantly inhibits the damage of PBX. The effect of interfacial shear strength on critical instability of PBX is approximately 1.7 times that of the interfacial tensile strength. Further, interface opening along the normal direction is the main damage form at the interface. Serrated and hemispherical rough interfaces can significantly inhibit propagation of cracks, and the load bearing capacity is improved by 22% and 9.7%, respectively. Appropriate improvement of the roughness of the interface structure can effectively improve the mechanical properties. It is significantly important to have a better understanding of deformation, damage and failure mechanisms of PBX and to improve our predictive ability.

Abstract We study the rotation effects of the hot and dense QCD matter in a non-perturbative regime by the gauge/gravity duality. We use the gravitational model that is designated to match the state-of-the-art lattice data on the thermal properties of (2+1)-flavor QCD and predict the location of the critical endpoint and the first-order phase transition line at large baryon chemical potential without rotation. After introducing the angular velocity via a local Lorentz boost, we investigate the thermodynamic quantities for the system under rotation in a self-consistent way. We find that the critical temperature and baryon chemical potential associated with the QCD phase transition decrease as the angular velocity increases. Moreover, some interesting phenomena are observed near the critical endpoint. We then construct the 3-dimensional phase diagram of the QCD matter in terms of temperature, baryon chemical potential, and angular velocity. As a parallel investigation, we also consider the gravitational model of SU(3) pure gluon system, for which the 2-dimensional phase diagram associated with temperature and angular velocity has been predicted. The corresponding thermodynamic quantities with rotation are investigated.

Abstract In this phase I study, the safety, pharmacokinetics, and antitumour activity of the HER2-targeted antibody–drug conjugate A166 were evaluated in patients with HER2-expressing advanced solid tumours. Patients with advanced solid tumours refractory to standard therapies received A166 at doses of 0.1, 0.3, 0.6, 1.2, 2.4, 3.6, 4.8 or 6.0 mg/kg Q3W in a standard “3 + 3” design. Dose cohorts were expanded at 4.8 and 6.0 mg/kg Q3W. Primary endpoints were assessment of the safety and tolerability of A166 and identification of the maximum tolerated dose or recommended phase II dose. In total, 81 patients were enroled and received A166 (n = 1 for 0.1 mg/kg; n = 3 for each of 0.3, 0.6, 1.2, 2.4 and 3.6 mg/kg doses; n = 27 for 4.8 mg/kg; n = 38 for 6.0 mg/kg). No dose-limiting toxicity or drug-related deaths occurred. The most common treatment-related adverse events at grade 3 or higher were corneal epitheliopathy (30.9%), blurred vision (18.5%), dry eyes (7.4%), and peripheral sensory neuropathy (6.2%). The Cmax and area under the curve of Duo-5, its free payload, were approximately 0.1% and 0.2% of those of the ADC, respectively. For all assessable HER2-positive breast cancer patients enroled in the 4.8 mg/kg and 6.0 mg/kg cohorts, the corresponding ORRs were 73.9% (17/23) and 68.6% (24/35), respectively, and the median PFS was 12.3 and 9.4 months, respectively. A166 has a recommended phase II dose of 4.8 mg/kg Q3W, manageable toxicity, good stability in the circulation and promising antitumour activities in HER2-positive breast cancer patients.

Abstract Applying the system of linear partial differential equations derived from the Mellin–Barnes representation and the Miller transformation, we present the GKZ-system of the Feynman integral of the 2-loop self energy diagram with 4 propagators. The codimension of the derived GKZ-system equals the number of independent dimensionless ratios among the external momentum squared and virtual mass squared. In total 536 hypergeometric functions are obtained in the neighborhoods of the origin and infinity, in which 30 linearly independent hypergeometric functions whose convergent regions have nonempty intersection constitute a fundamental solution system in a proper subset of the whole parameter space.