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The growing interest to develop modern digital displays and colour printing has driven the advancement of colouration technologies with remarkable speed. In particular, metasurface-based structural colouration shows a remarkable high colour saturation, wide gamut palette, chiaroscuro presentation and polarization tunability. However, previous approaches cannot simultaneously achieve all these features. Here, we design and experimentally demonstrate a surface-relief plasmonic metasurface consisting of shallow nanoapertures that enable the independent manipulation of colour hue, saturation and brightness by individually varying the geometric dimensions and orientation of the nanoapertures. We fabricate microscale artworks using a reusable template-stripping technique that features photorealistic and stereoscopic impressions. In addition, through the meticulous arrangement of differently oriented nanoapertures, kaleidoscopic information states can be decrypted by particular combinations of incident and reflected polarized light.

It's well-known that multiple metal elements can lead to the change of oxidative stress response levels in vivo. However, their relationship with age-related cataract (ARC) had not been well studied. We designed a case-control study including 210 individuals with ARC and 210 matched control group. The metal levels in their urine specimens were measured using graphite furnace atomic absorption spectrometry (GFAAS) and inductively coupled plasma optical emission spectrometry (ICP-OES). Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to select representative metals into the multi-element model and reduce dimension. Multivariate logic analysis and Bayesian kernel machine regression (BKMR) were subsequently used to explore the association of ARC risk with multiple metal elements. We found that magnesium (Mg), chromium (Cr), arsenic (As), manganese (Mn), and selenium (Se) were positively associated with ARC in the single-element model. The multiple exposure model indicated a positive association between Mg and As, in which the OR in their highest quartile were 3.32 (95% CI: 1.24-8.89) and 7.09 (95% CI: 2.56-19.63). The BKMR model also showed the effect of As increased monotonically with its increasing concentration, and high levels of Mg and As had a significant positive effect on ARC risk. In conclusion, we found that exposure to multiple metals was associated with increased ARC risk. Further research is needed to verify these findings in the future.

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.

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.

Objective The accurate preoperative differentiation of benign and malignant adnexal masses, especially those with complex ultrasound morphology, remains a great challenge for junior sonographers. The purpose of this study was to develop and validate a nomogram based on the Ovarian-Adnexal Reporting and Data System (O-RADS) for predicting the malignancy risk of adnexal masses with complex ultrasound morphology. Methods A total of 243 patients with data on adnexal masses with complex ultrasound morphology from January 2019 to December 2020 were selected to establish the training cohort, while 106 patients with data from January 2021 to December 2021 served as the validation cohort. Univariate and multivariate analyses were used to determine independent risk factors for malignant tumors in the training cohort. Subsequently, a predictive nomogram model was developed and validated in the validation cohort. The calibration, discrimination, and clinical net benefit of the nomogram model were assessed separately by calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). Finally, we compared this model to the O-RADS. Results The O-RADS category, an elevated CA125 level, acoustic shadowing and a papillary projection with color Doppler flow were the independent predictors and were incorporated into the nomogram model. The area under the ROC curve (AUC) of the nomogram model was 0.958 (95% CI, 0.932–0.984) in the training cohort. The specificity and sensitivity were 0.939 and 0.893, respectively. This nomogram also showed good discrimination in the validation cohort (AUC = 0.940, 95% CI, 0.899–0.981), with a sensitivity of 0.915 and specificity of 0.797. In addition, the nomogram model showed good calibration efficiency in both the training and validation cohorts. DCA indicated that the nomogram was clinically useful. Furthermore, the nomogram model had higher AUC and net benefit than the O-RADS. Conclusion The nomogram based on the O-RADS showed a good predictive ability for the malignancy risk of adnexal masses with complex ultrasound morphology and could provide help for junior sonographers.

Pain is a common symptom of an illness. For decades, pain treatments such as non-steroidal anti-inflammatory drugs, opioids, and surgical nerve blocking have been widely used, but each method has its limitations. Photobiomodulation is a recently developed method for pain management, with light-emitting diodes (LEDs) being a more recent development used in pain management because of their low cost, low side effects, and high safety. Here, we reviewed the phototherapeutic effects of LEDs on different pain conditions. We also discussed possible physicochemical and neurobiological mechanisms underlying LED therapy, especially its effects on inflammatory pain.

Background Patients with unilateral cleft lip and palate were associated with different nasomaxillary complex from the normal population. Although the biomechanical effects of conventional rapid palatal expansion (Hyrax expansion) and bone-borne rapid palatal expansion (micro-implant-assisted expansion) in non-cleft patients have been identified by multiple studies, little is known in patients with unilateral cleft lip and palate. The purpose of this study was to investigate and compare the biomechanical effects of the conventional and bone-borne palatal expanders in a late adolescence with unilateral cleft lip and palate. Methods A cone beam CT scan of a late adolescence with unilateral cleft lip and palate was selected to construct the three-dimensional finite element models of teeth and craniofacial structures. The models of conventional and born-borne palatal expanders were established to simulate the clinical maxillary expansion. The geometric nonlinear theory was applied to evaluate the Von Mises stress distribution and displacements in craniofacial structures and teeth. Results Bone-borne palatal expander achieved more transverse movement than conventional palatal expander in the whole mount of craniofacial regions, and the maximum amount of expansion was occurred anteriorly along the alveolar ridge on cleft-side. The expanding force from born-borne palatal expander resulted in more advancement in nasomaxillary complex than it in conventional palatal expander, especially in the anterior area of the minor segment of maxilla. Stresses from the both expanders distributed in similar patterns, but larger magnitudes and ranges were generated using the bone-borne expander around the maxillary buttresses and pterygoid plates of sphenoid bone. The maximum expanding stresses from born-borne palatal expander were concentrated on palatal slope supporting minscrews, whereas those from conventional palatal expander were concentrated on the anchoring molars. In addition, the buccal tipping effect of teeth generated using the bone-borne expander was less than it using the conventional palatal expander. Conclusion Bone-borne expander generated enhanced skeletal expansion at the levels of alveolar and palate in transversal direction, where the miniscrews contributed increased expanding forces to maxillary buttresses and decreased forces to buccal alveolar. Bone-borne expanders presented a superiority in correcting the asymmetric maxilla without surgical assistant in late adolescence with unilateral cleft lip and palate.

Objectives Esophageal cancer is a high-mortality disease. Esophagectomy is the most effective method to treat esophageal cancer, accompanied with a high incidence of post-operation complications. The anastomosis has a close connection to many severe post-operation complications. However, it remains controversial about the choice of intrathoracic anastomosis (IA) or cervical anastomosis (CA). The study was conducted to compare the clinical outcomes between the two approaches. Methods We searched databases for both randomized controlled trials (RCTs) and cohort studies comparing post-operation outcomes between IA and CA. Primary outcomes were the incidences of anastomotic leakage and mortality. Secondary outcomes were the incidences of anastomotic stenosis, pneumonia and re-operation. Results Twenty studies with a total of 7,479 patients (CA group: n = 3,183; IA group: n = 4296) were included. The results indicated that CA group had a higher incidence of anastomotic leakage than IA group (odds ratio [OR] = 2.05, 95% confidence intervals [CI] = 1.61–2.60, I2 = 53.31%, P 2 = 0.00%, P = 0.04) and type II (OR = 2.75, 95%CI = 1.95–3.88, I2 = 1.80%, P 2 = 20.92%, P = 0.31). The 90-day mortality (OR = 1.66, 95%CI = 1.11–2.47, I2 = 0.0%, P = 0.01) in IA group were lower than that in CA group. No difference was found in in-hospital mortality (OR = 1.31, 95%CI = 0.91–1.88, I2 = 0.00%, P = 0.15) and 30-day mortality (OR = 1.08, 95%CI = 0.69–1.70, I2 = 0.00%, P = 0.74). Conclusions IA might be a better anastomotic approach than CA, with a lower incidence of anastomosis leakage and no increase in short-term mortality. Significant heterogeneity and publication bias might limit the reliability of the results. More high-quality studies are needed to verify and update our findings.

By using gauge/gravity duality, we calculate the spectral function of the heavy vector mesons with the presence of an intense magnetic field in a hot and dense medium. The results show that, a general conclusion, as the increases of magnetic field, chemical potential and temperature, the height of the peak of the spectral function decreases and the width increases. A nontrivial result is the change from the peak position of spectral function. We explain this non-trivial behavior by the interplay of the interaction between the two heavy quarks and the interaction between the medium with each of the heavy quarks.

For the non-destructive interrogation purpose, the present work studies the flexural wave propagation characteristics in submerged pipes conveying viscous flowing fluid. The internal fluid-pipe and external fluid-pipe coupling effects are both considered. The internal fluid is assumed to be viscous, irrotational, and isotropic; and the external fluid is treated as ideal and irrotational. The pressures exerted on the pipe by the internal and external fluid can be derived via the Navier–Stokes equation. The pipe is modeled based on the first-order shear deformation shell theory. The motion equations of the submerged fluid-conveying pipe are given by the Hamilton’s Principle. The coupled equations of wave motion of the pipes are obtained based on the first-order shear deformation shell theory. The wave propagation relations of submerged pipes conveying viscous flowing fluid are given. Increasing internal fluid velocity, external fluid velocity, or reducing internal fluid mass density can result in an increase in phase velocity of the first flexural mode. In addition, the phase velocities of the first three flexural modes are almost constant under a large axial wave number.

The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.0198) and less time required for symptoms remission (P = 0.0194) than those who received placebo. Based on chest images, both severe and critical patients treated with MSCs showed improvement by day 7 (P = 0.0099) and day 21 (P = 0.0084). MSC-treated patients had fewer adverse events. MSC infusion reduced the levels of C-reactive protein, proinflammatory cytokines, and neutrophil extracellular traps (NETs) and promoted the maintenance of SARS-CoV-2-specific antibodies. To explore how MSCs modulate the immune system, we employed single-cell RNA sequencing analysis on peripheral blood. Our analysis identified a novel subpopulation of VNN2+ hematopoietic stem/progenitor-like (HSPC-like) cells expressing CSF3R and PTPRE that were mobilized following MSC infusion. Genes encoding chemotaxis factors — CX3CR1 and L-selectin — were upregulated in various immune cells. MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro. In addition, an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling. Together, our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis.

Somatosensory autonomic reflexes allow electroacupuncture stimulation (ES) to modulate body physiology at distant sites1–6 (for example, suppressing severe systemic inflammation6–9). Since the 1970s, an emerging organizational rule about these reflexes has been the presence of body-region specificity1–6. For example, ES at the hindlimb ST36 acupoint but not the abdominal ST25 acupoint can drive the vagal–adrenal anti-inflammatory axis in mice10,11. The neuroanatomical basis of this somatotopic organization is, however, unknown. Here we show that PROKR2Cre-marked sensory neurons, which innervate the deep hindlimb fascia (for example, the periosteum) but not abdominal fascia (for example, the peritoneum), are crucial for driving the vagal–adrenal axis. Low-intensity ES at the ST36 site in mice with ablated PROKR2Cre-marked sensory neurons failed to activate hindbrain vagal efferent neurons or to drive catecholamine release from adrenal glands. As a result, ES no longer suppressed systemic inflammation induced by bacterial endotoxins. By contrast, spinal sympathetic reflexes evoked by high-intensity ES at both ST25 and ST36 sites were unaffected. We also show that optogenetic stimulation of PROKR2Cre-marked nerve terminals through the ST36 site is sufficient to drive the vagal–adrenal axis but not sympathetic reflexes. Furthermore, the distribution patterns of PROKR2Cre nerve fibres can retrospectively predict body regions at which low-intensity ES will or will not effectively produce anti-inflammatory effects. Our studies provide a neuroanatomical basis for the selectivity and specificity of acupoints in driving specific autonomic pathways. Neuroanatomical findings demonstrate why electroactupuncture at only specific acupoints can drive the vagal–adrenal axis and treat inflammation in mice.

This work analyzes the free vibration of a spinning functionally graded graphene platelet-reinforced metal foam (FG-GPLRMF) beam. The differential transformation method is extended to analyze flap-wise bending vibration and chordwise bending vibration with Coriolis force effect for the first time. The beam is modeled using the Euler–Bernoulli beam theory. The Halpin–Tsai micromechanics model is utilized to predict effective material properties. Various types of graphene platelet (GPL) and porosity distributions are considered. The governing equations and corresponding boundary conditions of the FG-GPLRMF beam are obtained via Hamilton’s principle. Results show that the vibration characteristics of the FG-GPLRMF beam are affected by the GPL geometry size, types of porosity, and GPL distributions. Among different types of porosity, the Porosity-A causes the highest fundamental natural frequency, while the Porosity-B corresponds to the lowest one of the spinning FG-GPLRMF beam in most cases. Moreover, the GPL pattern and porosity distribution have a coupled effect on the bending vibration of the spinning FG-GPLRMF beam.

Two new isobenzofuranone derivatives (1 and 2) together with six known compounds (3–8) were isolated from the roots of Phlomis betonicoides, a highly sweet plant in China. Their structures were determined by means of HR-ESI-MS and extensive 1D and 2D NMR spectroscopic studies. Compounds 1–8 were tested for their anti-rotavirus activity. The results showed that compounds 1–8 exhibited potent anti-rotavirus activity with therapeutic index value 7.5–16.4.

Background C1q/TNF-related protein 9 (CTRP9) and adiponectin (APN) have beneficial metabolic regulatory and vasoprotective effects. This study explored alteration of CTRP9 and APN multimers during onset of ischemic stroke and development, to provide novel clinical and experimental basis for recognition and prevention of ischemic stroke. Methods There were 269 patients with ischemic stroke and 182 control subjects included in this study. Serum levels of CTRP9 and APN multimers in different disease stages were measured. Results Serum CTRP9, total APN (tAPN), and high-molecular weight (HMW) APN decreased gradually in stage I (acute stage, within 72 h of onset) of ischemic stroke and increased during stage III (11th day to one month) and stage IV (1 month after), compared to control. In the non-hyperlipidemia group, serum CTRP9, tAPN, and HMW were decreased in ischemic stroke patients compared to control (P r = 0.992, 0.991). Serum CTRP9 are protective against ischemic stroke (OR = 0.400, 95% CI 0.197–0.810, P Conclusions Lower serum CTRP9, tAPN, LMW, and HMW are significantly associated with increased ischemic stroke risk in non-hyperlipidemia subjects. CTRP9, tAPN, and HMW isoforms may be valuable clinical indicators for patients with ischemic stroke.

We study the mass spectra of $\bar{Q}Q\bar{Q}Q\ (Q=c,b)$ systems in QCD sum rules with the complete next-to-leading order (NLO) contribution to the perturbative QCD part of the correlation functions. Instead of meson-meson or diquark-antidiquark currents, we use diagonalized currents under operator renormalization. We find that differing from conventional mesons $\bar qq$ and baryons $qqq$, a unique feature of the multiquark systems like $\bar{Q}Q\bar{Q}Q$ is the operator mixing or color configuration mixing induced by NLO corrections, which is crucial to understand the color structure of the states. Our numerical results show that the NLO corrections are very important for the $\bar{Q}Q\bar{Q}Q$ system, because they not only give significant contributions but also reduce the scheme and scale dependence and make Borel platform more distinct, especially for the $\bar{b}b\bar{b}b$ in the $\overline{\rm{MS}}$ scheme. We use currents that have good perturbation convergence in our phenomenological analysis. With the $\overline{\rm{MS}}$ scheme, we get three $J^{PC}=0^{++}$ states, with masses $6.35^{+0.20}_{-0.17}$ GeV, $6.56^{+0.18}_{-0.20}$ GeV and $6.95^{+0.21}_{-0.31}$ GeV, respectively. The first two seem to agree with the broad structure around $6.2\sim6.8$ GeV measured by the LHCb collaboration in the $J/\psi J/\psi$ spectrum, and the third seems to agree with the narrow resonance $X(6900)$. For the $2^{++}$ states we find one with mass $7.03^{+0.22}_{-0.26}$ GeV, which is also close to that of $X(6900)$, and another one around $7.25^{+0.21}_{-0.35}$ GeV, which has good scale dependence but slightly large scheme dependence., Comment: 60 pages, 53 figures, nonrelativistic (NR) reductions of some operators are illustrated

Self-assembled architectures of soft matter have fascinated scientists for centuries due to their unique physical properties originated from controllable orientational and/or positional orders, and diverse optic and photonic applications. If one could know how to design, fabricate, and manipulate these optical microstructures in soft matter systems, such as liquid crystals (LCs), that would open new opportunities in both scientific research and practical applications, such as the interaction between light and soft matter, the intrinsic assembly of the topological patterns, and the multidimensional control of the light (polarization, phase, spatial distribution, propagation direction). Here, we summarize recent progresses in self-assembled optical architectures in typical thermotropic LCs and bio-based lyotropic LCs. After briefly introducing the basic definitions and properties of the materials, we present the manipulation schemes of various LC microstructures, especially the topological and topographic configurations. This work further illustrates external-stimuli-enabled dynamic controllability of self-assembled optical structures of these soft materials, and demonstrates several emerging applications. Lastly, we discuss the challenges and opportunities of these materials towards soft matter photonics, and envision future perspectives in this field.

Aberrant topological organization of whole-brain networks has been inconsistently reported in studies of patients with major depressive disorder (MDD), reflecting limited sample sizes. To address this issue, we utilized a big data sample of MDD patients from the REST-meta-MDD Project, including 821 MDD patients and 765 normal controls (NCs) from 16 sites. Using the Dosenbach 160 node atlas, we examined whole-brain functional networks and extracted topological features (e.g., global and local efficiency, nodal efficiency, and degree) using graph theory-based methods. Linear mixed-effect models were used for group comparisons to control for site variability; robustness of results was confirmed (e.g., multiple topological parameters, different node definitions, and several head motion control strategies were applied). We found decreased global and local efficiency in patients with MDD compared to NCs. At the nodal level, patients with MDD were characterized by decreased nodal degrees in the somatomotor network (SMN), dorsal attention network (DAN) and visual network (VN) and decreased nodal efficiency in the default mode network (DMN), SMN, DAN, and VN. These topological differences were mostly driven by recurrent MDD patients, rather than first-episode drug naive (FEDN) patients with MDD. In this highly powered multisite study, we observed disrupted topological architecture of functional brain networks in MDD, suggesting both locally and globally decreased efficiency in brain networks.

Post-heat treatment takes a key role for the enhancement of mechanical properties in selective laser melting (SLM) additive manufacturing (AM) of 6xxx series aluminum alloy. To understand the basic mechanism for changes of mechanical properties in the SLM process and the following post-heat treatment, the finite element model and the precipitate evolution (PE) model of SLM AM were established and combined. Results show that the hardness of the fabricated AM component can reach 91.47 HV at 170 °C for 18.8 h, which is 63.1% higher than the as-fabricated state. The comparison of hardness in as-fabricated AM component with experiments shows the validity of the proposed models. Further work on chemical composition shows that the selection of powder particle can greatly affect the hardness of the fabricated AM component. In the selection of 6xxx series aluminum alloy powder, higher Mg and Si contents in their solubility domains lead to higher generation of Mg2Si nano-size precipitates and then cause higher hardness of AM specimen. After the optimal post-heat treatment, the maximum hardness can exceed 100 HV.

The theoretical modeling of a functionally graded (FG) graphene nanoplatelet (GPL)-reinforced assembled beam–plate structure resting on elastic supports is presented for the first time, and its free vibration analysis is performed. Herein, the assembled structure is modeled according to the Kirchhoff plate theory and the Rayleigh beam theory. The graphene nanoplatelets (GPLs) gradiently distribute in the beam’s radial direction and in the plate’s thickness direction, respectively. By adopting the rule of mixture and the Halpin–Tsai model, the effective material properties can be obtained. By employing the Lagrange’s equation and considering the effects of Coriolis force and centrifugal force, the coupled governing equations of the assembled structure are determined. Furthermore, the assumed modes method and substructure modal synthesis method are applied to obtain the frequencies of the assembled beam–plate structure. A comprehensive numerical investigation is carried out to discuss the influence of the structural and material parameters on the vibration behavior of the beam–plate structure.

Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood–air barrier, blood–testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.

Background Malaria is a devastating infectious disease that disproportionally threatens hundreds of millions of people in developing countries. In the history of anti-malaria campaign, chloroquine (CQ) has played an indispensable role, however, its mechanism of action (MoA) is not fully understood. Methods We used the principle of photo-affinity labeling and click chemistry-based functionalization in the design of a CQ probe and developed a combined deconvolution strategy of activity-based protein profiling (ABPP) and mass spectrometry-coupled cellular thermal shift assay (MS-CETSA) that identified the protein targets of CQ in an unbiased manner in this study. The interactions between CQ and these identified potential protein hits were confirmed by biophysical and enzymatic assays. Results We developed a novel clickable, photo-affinity chloroquine analog probe (CQP) which retains the antimalarial activity in the nanomole range, and identified a total of 40 proteins that specifically interacted and photo-crosslinked with CQP which was inhibited in the presence of excess CQ. Using MS-CETSA, we identified 83 candidate interacting proteins out of a total of 3375 measured parasite proteins. At the same time, we identified 8 proteins as the most potential hits which were commonly identified by both methods. Conclusions We found that CQ could disrupt glycolysis and energy metabolism of malarial parasites through direct binding with some of the key enzymes, a new mechanism that is different from its well-known inhibitory effect of hemozoin formation. This is the first report of identifying CQ antimalarial targets by a parallel usage of labeled (ABPP) and label-free (MS-CETSA) methods.

The nucleus accumbens (NAc) is considered a hub of reward processing and a growing body of evidence has suggested its crucial role in the pathophysiology of major depressive disorder (MDD). However, inconsistent results have been reported by studies on reward network-focused resting-state functional MRI (rs-fMRI). In this study, we examined functional alterations of the NAc-based reward circuits in patients with MDD via meta- and mega-analysis. First, we performed a coordinated-based meta-analysis with a new SDM-PSI method for all up-to-date rs-fMRI studies that focused on the reward circuits of patients with MDD. Then, we tested the meta-analysis results in the REST-meta-MDD database which provided anonymous rs-fMRI data from 186 recurrent MDDs and 465 healthy controls. Decreased functional connectivity (FC) within the reward system in patients with recurrent MDD was the most robust finding in this study. We also found disrupted NAc FCs in the DMN in patients with recurrent MDD compared with healthy controls. Specifically, the combination of disrupted NAc FCs within the reward network could discriminate patients with recurrent MDD from healthy controls with an optimal accuracy of 74.7%. This study confirmed the critical role of decreased FC in the reward network in the neuropathology of MDD. Disrupted inter-network connectivity between the reward network and DMN may also have contributed to the neural mechanisms of MDD. These abnormalities have potential to serve as brain-based biomarkers for individual diagnosis to differentiate patients with recurrent MDD from healthy controls.

In the present study, we analyze the nonlinear forced vibration of thin-walled metal foam cylindrical shells reinforced with functionally graded graphene platelets. Attention is focused on the 1:1:1:2 internal resonances, which is detected to exist in this novel nanocomposite structure. Three kinds of porosity distribution and different kinds of graphene platelet distribution are considered. The equations of motion and the compatibility equation are deduced according to the Donnell’s nonlinear shell theory. The stress function is introduced, and then, the four-degree-of-freedom nonlinear ordinary differential equations (ODEs) are obtained via the Galerkin method. The numerical analysis of nonlinear forced vibration responses is presented by using the pseudo-arclength continuation technique. The present results are validated by comparison with those in existing literature for special cases. Results demonstrate that the amplitude–frequency relations of the system are very complex due to the 1:1:1:2 internal resonances. Porosity distribution and graphene platelet (GPL) distribution influence obviously the nonlinear behavior of the shells. We also found that the inclusion of graphene platelets in the shells weakens the nonlinear coupling effect. Moreover, the effects of the porosity coefficient and GPL weight fraction on the nonlinear dynamical response are strongly related to the porosity distribution as well as graphene platelet distribution.

A structure-based modeling of the CaO−‘FeO’−MgO−Al2O3−SiO2 system and its subsystems was investigated based on iron extraction from nickel slag by aluminum dross. Parameters optimization in the present model indicated that the coefficient of free O2− in FeO, $$a_{{{\text{O}}_{{{\text{FeO}}}}^{{2 - }} }}$$ , on the lengths of network linkage had the largest value and $${\text{O}}_{{{\text{FeO}}}}^{{2 - }}$$ (free O2− in FeO) had the largest mobility. The coefficients of bridging oxygen (aSi−O−Al and aAl−O−Al) were lower than those of non-bridging oxygen and free oxygen (O2−). Viscosity prediction for the CaO−‘FeO’−(8 wt.%) MgO−Al2O3−SiO2 system was conducted at a fixed slag basicity, which indicated that the predicted viscosity changed monotonously with the FeO content. However, the non-monotonous evolution with Al2O3 content reflected the amphoteric behavior of Al2O3. In addition, the performances of the present model in predicting viscosity from binary (‘FeO’−SiO2) to quinary (CaO−‘FeO’−MgO−Al2O3−SiO2) system were analyzed and a comparison with the established models was made.

Background Freshwater planarians of the genus Dugesia (Platyhelminthes, Tricladida, Dugesiidae) are distributed in a major part of the Old World and Australia, although until recently only very few species were known from China. Results Two new species of Dugesia from Southern China are described on the basis of an integrative taxonomic approach. BI and ML phylogenetic trees based on the independent genes and on the concatenated dataset had similar topologies, only differing in some nodes that were weakly supported. Phylogenetic trees based on the concatenated dataset revealed that D. adunca Chen & Sluys, sp. nov. and D. tumida Chen & Sluys, sp. nov. are not closely related and belong to different clades. The two new species occupy separate long branches with high support values and, thus, are well-differentiated from their congeners. Separate species status of D. adunca and D. tumida is supported also by the genetic distances between the species included in our analysis, albeit that COI distances varied greatly among species. Dugesia adunca from Guangxi Province is characterized by the following features: living mature animals rather small; asymmetrical openings of the oviducts into the bursal canal; penis papilla with shape of an aquiline bill, albeit with a blunt tip; asymmetrical penis papilla, with a large antero-dorsal lip and a much smaller ventro-posterior lip; very large seminal vesicle, provided with trabeculae; small diaphragm; mixoploid karyotype with diploid complements of 2n = 2x = 16 and triploid complements of 2n = 3x = 24, with all chromosomes being metacentric. Dugesia tumida from Guangdong Province is characterized by a penis papilla provided with a large, symmetrical penial valve from the middle of which arises the small, distal section of the papilla; a duct intercalated between the seminal vesicle and the small diaphragm; ventrally displaced ejaculatory duct curving upwards before opening to the exterior; penis papilla highly asymmetrical, having a slim and long ventral portion and a short and stubby dorsal part; vasa deferentia separately opening into antero-dorsal portion of seminal vesicle; oviducts openings symmetrically into ventral portion of the bursal canal, near its opening into the atrium; mixoploid karyotype, with diploid chromosome portraits of 2n = 2x = 16, and triploid complements of 2n = 3x = 24, with all chromosomes being metacentric. In the context of the various kinds of mixoploidy and the sexualization of specimens, reproductive modalities within the genus Dugesia are shortly discussed. Conclusion Molecular, morphological, and karyological markers show that the two populations examined represent members of the genus Dugesia and constitute two new, distinct species.

The accumulating evidence revealed that gut microbiota plays an important role in pathological process of disease including obesity, type 2 diabetes mellitus, heart failure, and non-alcoholic fatty liver disease. Polysaccharides extracted from Chinese medicine (CM) can not only alleviate pathological status but also promote health by anti-inflammatory, regulating immunity, lowering blood glucose and lipids, anti-cancer, and anti-oxidation. The alterations of gut microbiota composition and metabolism pathways are the potential mechanisms of CM polysaccharides treatment. In addition, they exert functions through gut-organ axis or play an indirect role by synergistic actions with other drugs or components mediated by gut microbiota. This review summarizes the molecular mechanisms of CM polysaccharides interacted with intestinal microbial inhabitants as potential prebiotics for promoting health.

Three ester-containing gemini surfactants (CmDEGs) were used to construct UV-responsive micellar systems with sodium trans-ortho-methoxycinnamate (trans-NaOMCA) as photo-sensitive additive. The effect of tail-chain length and spacer chain length on the UV-responsive ability was preliminarily explored. Longer tail chain and shorter spacer chain are favorable factors for enhancing UV-responsive ability. The addition of trans-NaOMCA into N,N′-bis(2-(dodecanoyloxy)ethyl)-N,N,N′,N′-tetramethyl-1,3-propane diammonium dibromide (C12DEG3) aqueous solution leads to a peak in zero-shear viscosity (η0) versus composition curve, and its further addition induces aqueous two-phase separation. For the C12DEG3/trans-NaOMCA/H2O mixed micellar systems, the UV responsiveness of significant decrease in η0 ascribes to microstructural transitions arising from the changes in counterion binding modes due to the trans-cis photoisomerization of NaOMCA. In comparison with the gemini surfactant 12-3-12, C12DEG3 has ester groups introduced in its tail chains. The introduction of ester groups leads to a significant effect on enhancing the photo-responsive ability in viscosity decrease of the constructed UV-responsive micellar systems. Furthermore, the effect of the addition of an amino acid–based surfactant sodium lauroylglutamate (SLGlu) into the C12DEG3/trans-NaOMCA/H2O mixed system on the UV-responsive behaviors was explored. In addition to UV-induced significant decrease in η0 and phase transition from aqueous two-phase systems (ATPS) to isotropic single-phase systems, the addition of SLGlu can also cause UV-induced increase in η0 and lead to richer UV-induced phase transition behaviors. The reason leading to these differences due to the presence of SLGlu was discussed based on 1H NMR spectra, molecular dynamics (MD) simulation, and molecular electrostatic potential (MEP) analysis.

Neck pain is very common, but most of the causes are unknown, making diagnosis and treatment extremely challenging. Current studies have found that one of the main problems in patients with neck pain is the impairment of cervical proprioception, which subsequently leads to cervical sensorimotor control disturbances. Cervical spine has a very delicate proprioceptive system that plays a crucial role in controlling posture and balance. Cervical proprioceptive impairment in neck pain occurs through a variety of mechanisms. Experimental neck muscle pain induced by injection of hypertonic saline results in inhibition of the activation of painful muscle; chronic neck pain causes structural and functional impairment of cervical muscles; excessive activation of mechanoreceptors in degenerative cervical discs and facet joints produces a large number of erroneous sensory signals. Clinical examinations to assess the link between structural pathology and neck pain have been unsuccessful, opening the way for the development of function-based tests. To date, eight neck sensorimotor control tests have been reported to evaluate patients with chronic neck pain. Although some tests may involve different subsystems (such as oculomotor system and vestibular system), all tests measure sensorimotor control in the neck, and the most commonly used is cervical joint position error (JPE) test. Current studies support the effectiveness of exercises targeting different aspects of sensorimotor function, in particular retraining aimed at improving cervical proprioception and muscle coordination. Based on the available evidence, it is recommended that patients with neck pain should be assessed and managed for cervical proprioceptive impairment and sensorimotor control disturbances.

An efficient method is developed to investigate the vibration and stability of moving plates immersed in fluid by applying the Kirchhoff plate theory and finite element method. The fluid is considered as an ideal fluid and is described with Bernoulli’s equation and the linear potential flow theory. Hamilton’s principle is used to acquire the dynamic equations of the immersed moving plate. The mass matrix, stiffness matrix, and gyroscopic inertia matrix are determined by the exact analytical integration. The numerical results show that the fundamental natural frequency of the submersed moving plates gradually decreases to zero with an increase in the axial speed, and consequently, the coupling phenomenon occurs between the first- and second-order modes. It is also found that the natural frequency of the submersed moving plates reduces with an increase in the fluid density or the immersion level. Moreover, the natural frequency will drop obviously if the plate is located near the rigid wall. In addition, the developed method has been verified in comparison with available results for special cases.

In this study, the dynamic response of buried fluid-conveying pipelines subjected to blast loading using the Love shell theory has been investigated. The fluid is considered as ideal fluid, and the velocity potential is used to describe the fluid pressure acting on the pipeline. The governing equations of the buried fluid-conveying pipelines are derived through Hamilton’s principle. The modal superposition method and the Newmark integral method are used to analyze the dynamic response of the pipelines under blast loading. Results show that the displacement amplitudes of the pipelines are larger in the soil with a higher acoustic impedance. The Winkler foundation can enhance the stiffness of the pipelines. Moreover, the increase in the scaled distance leads to the decrease in the displacement amplitudes of the pipelines. The increase in the fluid velocity results in the rise of the displacement amplitudes of the pipelines. In addition, the maximum displacement increases first and then decreases with the increase in length-to-radius ratio of the pipelines. With the increase in thickness-to-radius ratio, the maximum displacement of the pipelines tends to decrease.

Place attachment has been a research focus in the fields of park and recreation management. Place attachment plays an important role in promoting sustainable development of parks and mountain tourism destination, however, there are limited studies that identified the spatial patterns of place attachment, especially in the context of mountain tourism destinations in China. Also, the geospatial spectrum of visitors is usually broad, examining the multivariate relationships among spatial proximity, perceived authenticity, and place attachment are essential for mountain tourism destinations to promote destination image and strengthen emotional bonding with targeted visitor groups. In this study, we selected an iconic and highly visited park, Jiuzhai Valley National Park in China, as our study site and conducted an on-site visitor survey to collect 557 samples. Study uses factor analysis and the structure equation model to analyze the relationship among spatial proximity, perceived authenticity, and place attachment. Results validate the two-dimension structure of place attachment and perceived authenticity. Study findings suggest that spatial proximity has significant impacts on existential authenticity and place identity, but has no significant impacts on place dependence. Perceived authenticity has a positive impact on place attachment. Study results advance the theories of place attachment and provide effective strategies to enhance emotional attachment between visitors and mountain tourism destinations.

Herein, lignin derived hierarchical porous carbon (LHPC) supported Pd nanoparticles (Pd/LHPC) were synthesized and developed as advanced electrocatalysts for ethanol oxidation. In the Pd/LHPC, the special hierarchical porous carbon with the interconnected micropores and mesopores uniformly distribute on the surface and walls of macropores can provide facile transport for electroactive species and more reaction available surface. The Pd/LHPC exhibits larger specific electrochemically active surface area, higher electrocatalytic activity and better stability toward the oxidation of ethanol than the black carbon (Vulcan XC-72) supported Pd (Pd/XC-72) and commercial Pd/C electrocatalysts. The strategy reported will open a new road to effectively use industrial waste to synthesize advanced carbon material for efficient electrocatalysts and other electrochemical energy-conversion devices.

Two new coumarins, 6-hydroxymethyl-3-prenyl-7-methoxycoumarin (1) and 6-hydroxyethyl-3-prenyl-7- methoxycoumarin (2), together with three known coumarins (3–5), were isolated from the roots and stems of Yunyan-300, a variety of Nicotiana tabacum L. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1 and 2 were tested for their anti-methicillinresistant Staphylococcus aureus (anti-MRSA) activity and their antioxidant activity. The results revealed that compounds 1 and 2 showed good anti-MRSA inhibitions with IZD of 12.2 ± 1.8 and 11.8 ± 1.5 mm, respectively, and antioxidant activity with an IC50 value of 4.65 and 4.85 μg/mL, respectively.

A series of novel quinolinyl imidazolidin-2-imine nickel complexes with different substituents on the imidazolidin-2-imine ligand were synthesized and characterized. The complexes in the presence of methylaluminoxane (MAO) as a cocatalyst catalyzed the copolymerization of norbornene (N) and styrene (S) or para-chlorostyrene (CS) with high activity (up to 1070 kg·mol−1·h−1). The installation of sterically bulky substituents on the imidazolidine-2-imine ligand was effective for the increase of the molecular weight and the comonomer content, affording high molecular weight copolymers with tunable CS content (0.57 mol%–11.7 mol%), in which the existence of Cl group can provide reaction site for the further functionalization of copolymers as well as the synthesis of graft or cross-linked polymers. The linear relationship between the comonomer content and the glass transition temperature of the copolymers and the monomer reactivity ratios in the copolymerization indicated the formation of the expected functionalized cyclic olefin copolymers (COC).

Two new anti-tobacco mosaic virus (anti-TMV) xanthones, 4,7-dimethoxy-5-hydroxymethyl-1-methylxanthone (1) and 7-hydroxy-5-hydroxymethyl-4-methoxy-1-methylxanthone (2), were isolated from the whole plants of Comastoma pedunculatum. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1 and 2 showed high anti-TMV activity with inhibition rates of 48.5 and 63.6%, respectively. These rates are higher than that of positive control.

We study the fragmentation function of the gluon to color-octet 3S1 heavy quark-antiquark pair using the soft gluon factorization (SGF) approach, which expresses the fragmentation function in a form of perturbative short-distance hard part convoluted with one-dimensional color-octet 3S1 soft gluon distribution (SGD). The short distance hard part is calculated to the next-to-leading order in αs and all orders in velocity expansion. By deriving and solving the renormalization group equation of the SGD, threshold logarithms are resummed to all orders in perturbation theory. The comparison with gluon fragmentation function calculated in NRQCD factorization approach indicates that the SGF formula resums a series of velocity corrections in NRQCD which are important for phenomenological study.

Besides the normal hearing pathway known as air conduction (AC), sound can also transmit to the cochlea through the skull, known as bone conduction (BC). During BC stimulation, the cochlear walls demonstrate rigid body motion (RBM) and compressional motion (CPM), both inducing the basilar membrane traveling wave (TW). Despite numerous measuring and modeling efforts for the TW phenomenon, the mechanism remains unclear, especially in the case of BC. This paper proposes a 3D finite element cochlea model mimicking the TW under BC. The model uses a traditional “box model” form, but in a spiral shape, with two fluid chambers separated by the long and flexible BM. The cochlear fluid was enclosed by bony walls, the oval and round window membranes. Contingent boundary conditions and stimulations are introduced according to the physical basis of AC and BC. Particularly for BC, both RBM and CPM of the cochlea walls are simulated. Harmonic numerical solutions are obtained at multiple frequencies among the hearing range. The BM vibration amplitude ( $$U_{{{\text{BM}}}}$$ ) and its relation with volume displacement difference between the oval and round windows $$(\Delta {\text{Vol}})$$ , as well as the pressure difference at the base of the cochlea ( $$P_{{{\text{SV}}}} \left( 0 \right) - P_{{{\text{ST}}}} \left( 0 \right)$$ ), are analyzed. The simulated BM response at 12 mm from the base is peaked at about 3 k Hz, which is consistent with published experimental data. The TW properties under AC and BC are the same and have a common mechanism. (1) $$U_{{{\text{BM}}}}$$ is proportional to $${\Delta }Vol$$ at low frequencies. (2) $$U_{{{\text{BM}}}}$$ is also proportional to $$P_{{{\text{SV}}}} \left( 0 \right) - P_{{{\text{ST}}}} \left( 0 \right)$$ , within 5 dB error at high frequencies such as 16 k Hz. This study partly reveals the common quantitative relations between the TW and related factors under AC and BC hearing.

In this paper, free vibration of a metal foam core sandwich (MFCS) beam embedded in Winkler–Pasternak elastic foundation is studied using the Chebyshev collocation method (CCM). This method can achieve high precision within the range allowed by the effective number of bits of computers. Three foam distribution types along the thickness direction are considered for the core. The Timoshenko beam theory is adopted and Hamilton’s principle is utilized to derive the boundary conditions and governing equations of the model. The numerical results show that natural frequencies of the sandwich beam initially increase and then decrease with the rise in thickness of metal foam core. By arranging the foam distribution in the core, natural frequencies of the sandwich beam can be significantly changed. Moreover, natural frequencies of the uniform foam distribution beam are insensitive to the foam coefficient. For the beam with non-uniform foam distribution, however, the natural frequencies increase or decrease with the foam coefficient, depending closely on the foam type. In addition, the present method is validated by comparing with the published ones for special cases.