BIGH3 mediates apoptosis and gap junction failure in osteocytes during renal cell carcinoma bone metastasis progression.

Renal cell carcinoma (RCC) bone metastatis progression is driven by crosstalk between tumor cells and the bone microenvironment, which includes osteoblasts, osteoclasts, and osteocytes. RCC bone metastases (RCCBM) are predominantly osteolytic and resistant to antiresorptive therapy. The molecular mechanisms underlying pathologic osteolysis and disruption of bone homeostasis remain incompletely understood. We previously reported that BIGH3/TGFBI (transforming growth factor-beta-induced protein ig-h3, shortened to BIGH3 henceforth) secreted by colonizing RCC cells drives osteolysis by inhibiting osteoblast differentiation, impairing healing of osteolytic lesions, which is reversible with osteoanabolic agents. Here, we report that BIGH3 induces osteocyte apoptosis in both human RCCBM tissue specimens and in a preclinical mouse model. We also demonstrate that BIGH3 reduces Cx43 expression, blocking gap junction (GJ) function and osteocyte network communication. BIGH3-mediated GJ inhibition is blocked by the lysosomal inhibitor hydroxychloroquine (HCQ), but not osteoanabolic agents. Our results broaden the understanding of pathologic osteolysis in RCCBM and indicate that targeting the BIGH3 mechanism could be a combinational strategy for the treatment of RCCBM-induced bone disease that overcomes the limited efficacy of antiresorptives that target osteoclasts.

Stable Inverted Perovskite Solar Cells with Efficiency over 23.0% via Dual-Layer SnO2 on Perovskite.

Perovskite solar cells (PSCs) have shown great potential for reducing costs and improving power conversion efficiency (PCE). One effective method to achieve the latter is to use an all-inorganic charge transport layer (ICTL). However, traditional methods for crystallizing inorganic layers often result in the formation of a powder instead of a continuous film. To address this issue, we designed a dual-layer inorganic electron transport layer (IETL). This dual-layer structure consists of a layer of SnO2 nanocrystals (SnO2 NCs) deposited via a solution process and a dense SnO2 layer deposited through atomic layer deposition (ALD SnO2) to fill the cracks and gaps between the SnO2 NCs. PSCs having these dual-layer SnO2 ETLs achieved a high efficiency of 23.0%. This efficiency surpasses the recorded performance of ICTLs deposited on the perovskite. Furthermore, the PCE is comparable to that achieved with a C60 ETL. Moreover, the high-density structure of the ALD SnO2 layer inhibits the vertical migration of ions, resulting in improved thermal stability. After continuous heating at 85 °C in 10% humidity for 1000 h, the PCE of the dual-layer SnO2 structure decreased by 18%, whereas that of the C60/BCP structure decreased by 36%. The integration of dual-layer SnO2 into PSCs represents a significant advancement in achieving high-performance, commercially viable inverted monolithic PSCs or tandem solar cells.

Ceftazidime-Avibactam Combination Therapy versus Monotherapy for the Treatment Carbapenem-Resistant Gram-Negative Bacterial Infections: A Retrospective Observational Study.

Purpose: Since the introduction of ceftazidime-avibactam (CZA) in the Chinese market, accumulating clinical evidence has substantiated its efficacy in the treatment of infections caused by carbapenem-resistant gram-negative bacteria (CR-GNB). Nevertheless, an ongoing debate persists concerning the choice between monotherapy and combination therapy when devising clinical anti-infection protocols. Patients and Methods: This retrospective, single-center observational study enrolled patients with CR-GNB infections who received CZA treatment between December 2019 and August 2023. The primary outcome assessed was 30-day mortality, and the secondary outcome measured was 14-day bacterial clearance. A multivariate Cox regression model was used to identify variables that were independently associated with 30-day mortality rate. Results: Eighty-three patients were enrolled in the study; of which, 45 received CZA monotherapy, whereas 38 received combination therapy. The overall 30-day mortality rate was 31.3%, and no significant difference was observed in the 30-day mortality rates between the CZA combination therapy and monotherapy groups (31.6% vs 31.1%, p=0.963). After adjustment by propensity score matching, the 30-day mortality rate was not significantly different between the two groups (28.6% vs 31.4%, p=0.794). Multivariate COX analysis revealed that age and SOFA score were independent predictors of 30-day mortality. Conclusion: Combination therapy with CZA and other antimicrobials was not found to have an advantage over monotherapy in reducing the 30-day mortality rate.

On-chip optical wavefront shaping by transverse-spin-induced Pancharatanam-Berry phase.

Pancharatnam-Berry (PB) metasurfaces can be applied to manipulate the phase and polarization of light within subwavelength thickness. The underlying mechanism is attributed to the geometric phase originating from the longitudinal spin of light. Here, we demonstrate, to the best of our knowledge, a new type of PB geometric phase derived from the intrinsic transverse spin of guided light. Using full-wave numerical simulations, we show that the rotation of a metallic nano-bar sitting on a metal substrate can induce a geometric phase covering 2π full range for the surface plasmons carrying an intrinsic transverse spin. Especially, the geometric phase is different for the surface plasmons propagating in opposite directions due to spin-momentum locking. We apply the geometric phase to design metasurfaces to manipulate the wavefront of surface plasmons to achieve steering and focusing. Our work provides a new mechanism for on-chip light manipulations with potential applications in designing ultra-compact optical devices for imaging and sensing.

Comparison of the safety and effectiveness of the four-hook needle and hook wire for the preoperative positioning of localization ground glass nodules.

BACKGROUND: With the implementation of lung cancer screening programs, an increasing number of pulmonary nodules have been detected.Video-assisted thoracoscopic surgery (VATS) could provide adequate tissue specimens for pathological analysis, and has few postoperative complications.However, locating the nodules intraoperatively by palpation can be difficult for thoracic surgeons. The preoperative pulmonary nodule localization technique is a very effective method.We compared the safety and effectiveness of two methods for the preoperative localization of pulmonary ground glass nodules. METHODS: From October 2020 to April 2021, 133 patients who underwent CT-guided single pulmonary nodule localization were retrospectively reviewed. All patients underwent video-assisted thoracoscopic surgery (VATS) after successful localization. Statistical analysis was used to evaluate the localization accuracy, safety, information related to surgery and postoperative pathology information. The aim of this study was to evaluate the clinical effects of the two localization needles. RESULTS: The mean maximal transverse nodule diameters in the four-hook needle and hook wire groups were 8.97 ± 3.85 mm and 9.00 ± 3.19 mm, respectively (P = 0.967). The localization times in the four-hook needle and hook wire groups were 20.58 ± 2.65 min and 21.43 ± 3.06 min, respectively (P = 0.09). The dislodgement rate was significantly higher in the hook wire group than in the four-hook needle group (7.46% vs. 0, P = 0.024). The mean patient pain scores based on the visual analog scale in the four-hook needle and hook wire groups were 2.87 ± 0.67 and 6.10 ± 2.39, respectively (P = 0.000). All ground glass nodules (GGNs) were successfully resected by VATS. CONCLUSIONS: Preoperative pulmonary nodule localization with both a four-hook needle and hook wire is safe, convenient and effective.

Enhanced optical forces on coupled chiral particles at arbitrary order exceptional points.

Exceptional points (EPs)-non-Hermitian degeneracies at which eigenvalues and eigenvectors coalesce-can give rise to many intriguing phenomena in optical systems. Here, we report a study of the optical forces on chiral particles in a non-Hermitian system at EPs. The EPs are achieved by employing the unidirectional coupling of the chiral particles sitting on a dielectric waveguide under the excitation of a linearly polarized plane wave. Using full-wave numerical simulations, we demonstrate that the structure can give rise to enhanced optical forces at the EPs. Higher order EPs in general can induce stronger optical forces. In addition, the optical forces exhibit an intriguing "skin effect": the force approaches the maximum for the chiral particle at one end of the lattice. The results contribute to the understanding of optical forces in non-Hermitian systems and can find applications in designing novel optical tweezers for on-chip manipulations of chiral particles.

Evaluation of Tibial Hemodynamic Response to Glucose Tolerance Test in Young Healthy Males and Females.

The relationship between glucose metabolism and bone health remains underexplored despite its clinical relevance. This study utilized the oral glucose tolerance test (OGTT) and near-infrared spectroscopy (NIRS) to probe gender-specific disparities in tibial hemodynamic responses among young healthy adults. Twenty-eight healthy participants (14 males) aged 18-28 years old were recruited for this study. After ingesting a 75 g glucose solution, tibial hemodynamic responses were captured using NIRS in combination with a 5 min ischemic reperfusion technique, both before and at 30 min intervals for two hours post-glucose ingestion. Parameters measured included oxidative metabolic rate (via tissue saturation index [TSI]), immediate recovery slope after occlusion release (TSI10), and total recovery magnitude (ΔTSI). Post-glucose ingestion, both genders demonstrated a surge in blood glucose concentrations at every time point compared to baseline (p < 0.001, 0.002, 0.009, and 0.039 for males; p < 0.001, < 0.001, = 0.002, and 0.017 for females). Baseline tibial metabolic rate, TSI10, and ΔTSI did not significantly differ between males and females (p = 0.734, 0.839, and 0.164, respectively), with no discernible temporal effects in any hemodynamic parameters within each gender (p = 0.864, 0.308, and 0.399, respectively, for males; p = 0.973, 0.453, and 0.137, respectively, for females). We found comparable tibial hemodynamic responses to OGTT between genders. This study demonstrated the utility of NIRS in evaluating tibial hemodynamic responses to glucose ingestion through OGTT, enriching our understanding of the body's metabolic responses to glucose intake.

A multi-channel UNet framework based on SNMF-DCNN for robust heart-lung-sound separation.

Cardiopulmonary and cardiovascular diseases are fatal factors that threaten human health and cause many deaths worldwide each year, so it is essential to screen cardiopulmonary disease more accurately and efficiently. Auscultation is a non-invasive method for physicians' perception of the disease. The Heart Sounds (HS) and Lung Sounds (LS) recorded by an electronic stethoscope consist of acoustic information that is helpful in the diagnosis of pulmonary conditions. Still, inter-interference between HS and LS presented in both the time and frequency domains blocks diagnostic efficiency. This paper proposes a blind source separation （BSS）strategy that first classifies Heart-Lung-Sound (HLS) according to its LS features and then separates it into HS and LS. Sparse Non-negative Matrix Factorization (SNMF) is employed to extract the LS features in HLS, then proposed a network constructed by Dilated Convolutional Neural Network (DCNN) to classify HLS into five types by the magnitude features of LS. Finally, Multi-Channel UNet (MCUNet) separation model is utilized for each category of HLS. This paper is the first to propose the HLS classification method SNMF-DCNN and apply UNet to the cardiopulmonary sound separation domain. Compared with other state-of-the-art methods, the proposed framework in this paper has higher separation quality and robustness.

Directional dipole dice enabled by anisotropic chirality.

Directional radiation and scattering play an essential role in light manipulation for various applications in integrated nanophotonics, antenna and metasurface designs, quantum optics, etc. The most elemental system with this property is the class of directional dipoles, including the circular dipole, Huygens dipole, and Janus dipole. A unified realization of all three dipole types and a mechanism to freely switch among them are previously unreported, yet highly desirable for developing compact and multifunctional directional sources. Here, we theoretically and experimentally demonstrate that the synergy of chirality and anisotropy can give rise to all three directional dipoles in one structure at the same frequency under linearly polarized plane wave excitations. This mechanism enables a simple helix particle to serve as a directional dipole dice (DDD), achieving selective manipulation of optical directionality via different "faces" of the particle. We employ three "faces" of the DDD to realize face-multiplexed routing of guided waves in three orthogonal directions with the directionality determined by spin, power flow, and reactive power, respectively. This construction of the complete directionality space can enable high-dimensional control of both near-field and far-field directionality with broad applications in photonic integrated circuits, quantum information processing, and subwavelength-resolution imaging.

Hydrothermal Synthesis of Ni3TeO6 and Cu3TeO6 Nanostructures for Magnetic and Photoconductivity Applications.

Despite great attention toward transition metal tellurates especially M3TeO6 (M = transition metal) in magnetoelectric applications, control on single phasic morphology-oriented growth of these tellurates at the nanoscale is still missing. Herein, a hydrothermal synthesis is performed to synthesize single-phased nanocrystals of two metal tellurates, i.e., Ni3TeO6 (NTO with average particle size ∼37 nm) and Cu3TeO6 (CTO ∼ 140 nm), using NaOH as an additive. This method favors the synthesis of pure NTO and CTO nanoparticles without the incorporation of Na at pH = 7 in MTO crystal structures such as Na2M2TeO6, as it happens in conventional synthesis approaches such as solid-state reaction and/or coprecipitation. Systematic characterization techniques utilizing in-house and synchrotron-based characterization methods for the morphological, structural, electronic, magnetic, and photoconductivity properties of nanomaterials showed the absence of Na in individual particulate single-phase MTO nanocrystals. Prepared MTO nanocrystals also exhibit slightly higher antiferromagnetic interactions (e.g., T N-NTO = 57 K and T N-CTO = 68 K) compared to previously reported MTO single crystals. Interestingly, NTO and CTO show not only a semiconducting nature but also photoconductivity. The proposed design scheme opens the door to any metal tellurates for controllable synthesis toward different applications. Moreover, the photoconductivity results of MTO nanomaterials prepared serve as a preliminary proof of concept for potential application as photodetectors.

Case Report: Clinical benefit from multi-target tyrosine kinase inhibitor and PARP inhibitor in a patient with cancer of unknown primary with BRCA1 large genomic rearrangement.

Background: Cancer of unknown primary (CUP), which accounts for 3%-5% of new cancer cases every year, involves the presence of a type of histologically confirmed metastatic tumors whose primary site cannot be confirmed by conventional diagnostic methods. This difficulty in identifying the primary site means that CUP patients fail to receive precisely targeted therapy. Most patients are treated with empiric chemotherapy, with a median survival of 6 months and even poorer prognosis within an unfavorable subset of CUP. Case report: An 80-year-old woman presented with masses in the abdomen. Following comprehensive imagological and immunohistochemical examinations, she was diagnosed with CUP. She emphatically declined chemotherapy; thus, anlotinib has been administered with patient consent since 02/07/2019, and stable disease (SD) was observed for 2 years. During subsequent treatment, a large genomic rearrangement in BRCA1 was identified in the patient via NGS, and SD was observed for a further 6 months following olaparib treatment. The type of LGR identified in this patient was discovered to be BRCA1 exon 17-18 inversion (inv), which has never been previously reported. Conclusion: For CUP patients, a chemo-free regimen seems to be acceptable as a first-line treatment, and NGS-guided targeted treatment could improve patient outcomes.

Co-precipitation of Mg-doped Ni0.8Co0.1Mn0.1(OH)2: effect of magnesium doping and washing on the battery cell performance.

Co-precipitation of Ni0.8Co0.1Mn0.1(OH)2 (NCM811) and Mg-doped (0.25 wt% and 0.5 wt%) NCM811 precursors is carried out from concentrated metal sulphate solutions. In this paper, the aim is to study the role of magnesium dopant in the co-precipitation step of NCM811, the cathode active material and further the Li-ion battery cell performance. Based on the results, magnesium was fully co-precipitated in the NCM811 precursors, as expected from thermodynamic calculations. The presence of magnesium in these precursors was also confirmed by several characterization methods and magnesium was evenly distributed in the sample. It was observed that tapped density decreased and surface area increased with an expected increase in Mg content. Surprisingly, Mg doping did not improve the cyclability of coin cells, due to the stable crystal structure of NCM811. However, a slight improvement in cyclability was seen in pouch cells after 1000 cycles. A washing effect was clearly seen in lattice parameters and washing also decreased the capacity retention after 62 cycles for all samples.

Method to Inhibit Perovskite Solution Aging: Induced by Perovskite Microcrystals.

The main feature of perovskite solar cells (PSCs) is that the perovskite layer can be fabricated by the solution method, while the long-time stability of the precursor solution is critical. During the fabrication of formamidinium (FA)-based PSCs, the introduction of methylammonium cations (MA+) in the precursor solution can accelerate the crystallization process of the perovskite layer, stabilize the perovskite structure, and passivate defects. However, MA+ is easy to deprotonate to generate MA molecules, and it then condensates with formamidinium iodide (FAI) to form adverse byproducts. Herein, perovskite microcrystals (MCs) for preparing perovskite precursor solution were investigated in details, which can improve the long-term stability of the precursor solution and the perovskite film. We found that FA+ in MC solution was confined in the three-dimensional scaffold, preventing it from reacting with MA+. Meanwhile, MCs can effectively promote nucleation to form large grains in perovskite films. The photoelectric conversion efficiency (PCE) of the device with 3 week-aged MC solution remains at 90% and is only reduced by 10% after 160 h of continuous operation, which far exceeds the performance of the PCE of those based on mixed monomer powder (MP) solution. Therefore, perovskite MCs, an effective reactive inhibitor to improve the stability of perovskite precursor solutions, are of great significance for large-scale commercial fabrication.

Light funneling by spin-orbit-coupled chiral particles on an arbitrary order exceptional surface.

Optical systems at non-Hermitian exceptional points (EPs) have intriguing properties that promise novel applications in light manipulations. Here, we realize an arbitrary order exceptional surface (ES), i.e., a surface of arbitrary order EPs, in chiral particles that couple with each other via the photonic spin-orbit interaction mediated by a dielectric waveguide. The chirality of the particles enables selective excitation of the chiral dipole modes by linearly polarized light. The unidirectional coupling of the chiral dipole modes gives rise to the ES in the parameter space defined by the material loss and coupling distance of the particles. We apply the system to realize a light funnel that can convert free-space plane waves to guided waves and funnel the incident light energy into a ring resonator. The results can find applications in designing optical switches, on-chip conversion of guided waves, and harvest of light energy.

Stable optical lateral forces from inhomogeneities of the spin angular momentum.

Transverse spin momentum related to the spin angular momentum (SAM) of light has been theoretically studied recently and predicted to generate an intriguing optical lateral force (OLF). Despite extensive studies, there is no direct experimental evidence of a stable OLF resulting from the dominant SAM rather than the ubiquitous spin-orbit interaction in a single light beam. Here, we theoretically unveil the nontrivial physics of SAM-correlated OLF, showing that the SAM is a dominant factor for the OLF on a nonabsorbing particle, while an additional force from the canonical (orbital) momentum is exhibited on an absorbing particle due to the spin-orbit interaction. Experimental results demonstrate the bidirectional movement of 5-µm-diameter particles on both sides of the beam with opposite spin momenta. The amplitude and sign of this force strongly depend on the polarization. Our optofluidic platform advances the exploitation of exotic forces in systems with a dominant SAM, facilitating the exploration of fascinating light-matter interactions.

Nonreciprocal light propagation induced by a subwavelength spinning cylinder.

Nonreciprocal optical devices have broad applications in light manipulations for communications and sensing. Non-magnetic mechanisms of optical nonreciprocity are highly desired for high-frequency on-chip applications. Here, we investigate the nonreciprocal properties of light propagation in a dielectric waveguide induced by a subwavelength spinning cylinder. We find that the chiral modes of the cylinder can give rise to unidirectional coupling with the waveguide via the transverse spin-orbit interaction, leading to different transmissions for guided wave propagating in opposite directions and thus optical isolation. We reveal the dependence of the nonreciprocal properties on various system parameters including mode order, spinning speed, coupling distance, and various losses. The results show that higher-order chiral modes and larger spinning speed generally give rise to stronger nonreciprocity, and there exists an optimal cylinder-waveguide coupling distance where the optical isolation reaches the maximum. The properties are sensitive to the material loss of the cylinder but show robustness against surface-roughness-induced loss in the waveguide. Our work contributes to the understanding of nonreciprocity in subwavelength moving structures and can find applications in integrated photonic circuits, topological photonics, and novel metasurfaces.

Fused Cycloheptatriene-BODIPY Is a High-Performance Near-Infrared Probe to Image Tau Tangles.

Neurofibrillary tangles (NFTs), which are composed of abnormally hyperphosphorylated Tau, are one of the main pathologic hallmarks of Alzheimer's disease and other tauopathies. The fluorescent imaging probes currently used to target NFTs cannot distinguish them well from ß-amyloid plaques, thus limiting their utility to diagnose diseases. Here, we developed a fused cycloheptatriene-BODIPY derivative (TNIR7-1A) that displays properties favorable for near-infrared (NIR) imaging with high affinity and specificity to NFTs in vitro. In addition, TNIR7-1A effectively penetrated the blood-brain barrier and clearly distinguished tauopathy in transgenic mice (rTg4510) from control mice using NIR fluorescence imaging in vivo. The sensitivity and specificity of TNIR7-1A for NFTs were confirmed ex vivo by fluorescence staining of the tauopathy mouse model, while molecular docking studies indicated that TNIR7-1A bound to NFTs through hydrophobic interactions. These results suggest that TNIR7-1A can act as a high-performance probe to detect NFTs in vitro and in vivo selectively.

Optical force and torque on small particles induced by polarization singularities.

Optical forces in the near fields have important applications in on-chip optical manipulations of small particles and molecules. Here, we report a study of optical force and torque on small particles induced by the optical polarization singularities of a gold cylinder. We show that the scattering of the cylinder generates both electric and magnetic C lines (i.e., lines of polarization singularities) in the near fields. The intrinsic spin density of the C lines can induce complex optical torque on a dielectric/magnetic particle, and the near-field evolutions of the C lines are accompanied by a gradient force on the particle. The force and torque manifest dramatic spatial variations, providing rich degrees of freedom for near-field optical manipulations. The study, for the first time to our knowledge, uncovers the effect of optical polarization singularities on light-induced force and torque on small particles. The results contribute to the understanding of chiral light-matter interactions and can find applications in on-chip optical manipulations and optical sensing.

Topological near fields generated by topological structures.

The central idea of metamaterials and metaoptics is that, besides their base materials, the geometry of structures offers a broad extra dimension to explore for exotic functionalities. Here, we discover that the topology of structures fundamentally dictates the topological properties of optical fields and offers a new dimension to exploit for optical functionalities that are irrelevant to specific material constituents or structural geometries. We find that the nontrivial topology of metal structures ensures the birth of polarization singularities (PSs) in the near field with rich morphologies and intriguing spatial evolutions including merging, bifurcation, and topological transition. By mapping the PSs to non-Hermitian exceptional points and using homotopy theory, we extract the core invariant that governs the topological classification of the PSs and the conservation law that regulates their spatial evolutions. The results bridge singular optics, topological photonics, and non-Hermitian physics, with potential applications in chiral sensing, chiral quantum optics, and beyond photonics in other wave systems.

Intratumoral CD8+ T cells as a potential positive predictor of chemoimmunotherapy response in PD-L1-negative advanced gastric cancer patients: a retrospective cohort study.

Background: Previous studies have shown that PD-L1-positive advanced gastric cancer (GC) patients could achieve clinical benefit after receiving immune checkpoint inhibitors (ICI) in initial or subsequent therapy. A number of prospective studies such as Keynote-158 have demonstrated that PD-L1-negative patients who tested as microsatellite instability-high (MSI-H) or tumor mutational burden-high (TMB-H) can benefit from ICIs. In the search for more biomarker for immunotherapy, some studies showed that patients with a specific characteristic to tumor microenvironment (TME) were associated with better prognosis. This study aimed to explore the association between the TME and immunotherapy in PD-L1 negative GC patients. Methods: This study was a retrospective cohort study. Twenty-six CPS PD-L1 negative stage IV advanced GC patients treated with chemoimmunotherapy in Shenzhen Hospital of Peking University were retrospectively enrolled according to the inclusion criteria. Their clinical characteristics were assessed and recorded by independent clinicians. Follow-up data was conducted through the Internet or visit. Respond to treatment was evaluated by RECIST 1.1. The primary outcome was progression-free survival (PFS). The level of tumor-infiltrating lymphocytes (TILs) was measured by multiplex immunofluorescence (mIF) among these patients. Cox proportional hazards analysis was performed to analyzed the correlation between PFS and clinical characteristics including TILs. Results: Among 26 patients, 5 patients (19.2%) were on complete response (CR) and 9 patients (34.6%) were in partial response (PR), while 7 patients (26.9%) experienced stable disease (SD). Intratumoral CD8+ T cells were obviously increased in CPS PD-L1 negative patients who responded to chemoimmunotherapy, compared with patients who did not respond (P=0.011). And higher level of CD8+ TILs was demonstrated to associate with better PFS in CPS PD-L1-negative patients treated with chemoimmunotherapy (HR =23.70, 95% CI: 1.15-488.30, P=0.04). Conclusions: Intratumoral CD8+ TILs may be a potential positive predictive factor of clinical response for chemoimmunotherapy in PD-L1-negative advanced GC. However, the results need to be further confirmed in a cohort with more subjects due to a limited sample sizes in present study.