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The accurate identification of pulmonary nodules is critical for the early diagnosis of lung diseases; however, this task remains challenging due to inadequate feature representation and limited localization sensitivity. Current methodologies often utilize channel attention mechanisms and intersection over union (IoU)-based loss functions. Yet, they frequently overlook spatial context and struggle to capture subtle variations in aspect ratios, which hinders their ability to detect small objects. In this study, we introduce an improved YOLOV11 framework that addresses these limitations through two primary components: a spatial squeeze-and-excitation (SSE) module that concurrently models channel-wise and spatial attention to enhance the discriminative features pertinent to nodules and explicit aspect ratio penalty IoU (EAPIoU) loss that imposes a direct penalty on the squared differences in aspect ratios to refine the bounding box regression process. Comprehensive experiments conducted on the LUNA16, LungCT, and Node21 datasets reveal that our approach achieves superior precision, recall, and mean average precision (mAP) across various IoU thresholds, surpassing previous state-of-the-art methods while maintaining computational efficiency. Specifically, the proposed SSE module achieves a precision of 0.781 on LUNA16, while the EAPIoU loss boosts mAP@50 to 92.4% on LungCT, outperforming mainstream attention mechanisms and IoU-based loss functions. These findings underscore the effectiveness of integrating spatially aware attention mechanisms with aspect ratio-sensitive loss functions for robust nodule detection.

Joint pain is the defining symptom of osteoarthritis (OA) but its origin and mechanisms remain unclear. Here, we investigated an unprecedented role of osteoclast-initiated subchondral bone remodeling in sensory innervation for OA pain. We show that osteoclasts secrete netrin-1 to induce sensory nerve axonal growth in subchondral bone. Reduction of osteoclast formation by knockout of receptor activator of nuclear factor kappa-B ligand (Rankl) in osteocytes inhibited the growth of sensory nerves into subchondral bone, dorsal root ganglion neuron hyperexcitability, and behavioral measures of pain hypersensitivity in OA mice. Moreover, we demonstrated a possible role for netrin-1 secreted by osteoclasts during aberrant subchondral bone remodeling in inducing sensory innervation and OA pain through its receptor DCC (deleted in colorectal cancer). Importantly, knockout of Netrin1 in tartrate-resistant acid phosphatase-positive (TRAP-positive) osteoclasts or knockdown of Dcc reduces OA pain behavior. In particular, inhibition of osteoclast activity by alendronate modifies aberrant subchondral bone remodeling and reduces innervation and pain behavior at the early stage of OA. These results suggest that intervention of the axonal guidance molecules (e.g., netrin-1) derived from aberrant subchondral bone remodeling may have therapeutic potential for OA pain.

Whether coupling auxiliary information (except for conventional rainfall–runoff and temperature data) into hydrological models can improve model performance and transferability is still an open question. In this study, we chose a glacier catchment to test the effect of auxiliary information, i.e., distributed forcing input, topography, snow-ice accumulation and melting on model calibration–validation and transferability. First, we applied the point observed precipitation and temperature as forcing data, to test the model performance in calibration–validation and transferability. Second, we took spatial distribution of forcing data into account, and did the same test. Third, the aspect was involved to do an identical experiment. Finally, the snow–ice simulation was used as part of the objective function in calibration, and to conduct the same experiment. Through stepwisely accounting these three pieces of auxiliary information, we found that a model without involving forcing data distribution, local relief, or snow–ice data can also perform well in calibration, but adding forcing data distribution and topography can dramatically increase model validation and transferability. It is also remarkable that including the snow–ice simulation into objective function did not improve model performance and transferability in this study. This may be because the well-gauged hydro-meteorological data are sufficient to constrain a well-designed hydrological model.

Exogenous growth factors could accelerate the process of wound healing. However, the underlying mechanisms have not been clearly clarified. The aim of the present study was to investigate the effect of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) on the expression of type I collagen (cola1), type III collagen (cola3), and Elastin in fibroblasts, which are widely expressed in fibroblasts and promote the function of fibroblasts. We measured the levels of cola1 and cola3 in human fibroblast cells cultured in medium containing EGF or bFGF at concentrations ranging from 0.1 to 1000 μg/L by Western blotting and RT-PCR assays, and found that EGF or bFGF enhanced the expression of cola1 and cola3 in a concentration-dependent manner. We further discovered that after stimulation with EGF or bFGF in human fibroblast cells, mitogen-activated protein kinases (MAPK) family members were generally activated, whose expression trend was consistent with that of cola1, cola3, and Elastin. In summary, in this study, we uncovered that exogenous growth factors enhance the expression of cola1, cola3, and Elastin, which is probably regulated via activating MAPK signaling pathway.

Degenerative disc disease (DDD) is associated with intervertebral disc degeneration of spinal instability. Here, we report that the cilia of nucleus pulposus (NP) cells mediate mechanotransduction to maintain anabolic activity in the discs. We found that mechanical stress promotes transport of parathyroid hormone 1 receptor (PTH1R) to the cilia and enhances parathyroid hormone (PTH) signaling in NP cells. PTH induces transcription of integrin αvβ6 to activate the transforming growth factor (TGF)-β-connective tissue growth factor (CCN2)-matrix proteins signaling cascade. Intermittent injection of PTH (iPTH) effectively attenuates disc degeneration of aged mice by direct signaling through NP cells, specifically improving intervertebral disc height and volume by increasing levels of TGF-β activity, CCN2, and aggrecan. PTH1R is expressed in both mouse and human NP cells. Importantly, knockout PTH1R or cilia in the NP cells results in significant disc degeneration and blunts the effect of PTH on attenuation of aged discs. Thus, mechanical stress-induced transport of PTH1R to the cilia enhances PTH signaling, which helps maintain intervertebral disc homeostasis, particularly during aging, indicating therapeutic potential of iPTH for DDD.

Joint pain is the defining symptom of osteoarthritis (OA) but its origin and mechanisms remain unclear. Here, we investigated an unprecedented role of osteoclast-initiated subchondral bone remodeling in sensory innervation for OA pain. We show that osteoclasts secrete netrin-1 to induce sensory nerve axonal growth in subchondral bone. Reduction of osteoclast formation by knockout of receptor activator of nuclear factor kappa-B ligand (Rank!) in osteocytes inhibited the growth of sensory nerves into subchondral bone, dorsal root ganglion neuron hyperexcitability, and behavioral measures of pain hypersensitivity in OA mice. Moreover, we demonstrated a possible role for netrin-1 secreted by osteoclasts during aberrant subchondral bone remodeling in inducing sensory innervation and OA pain through its receptor DCC (deleted in colorectal cancer). Importantly, knockout of Netrin1 in tartrate-resistant acid phosphatase-positive (TRAP- positive) osteoclasts or knockdown of Dcc reduces OA pain behavior. In particular, inhibition of osteoclast activity by alendronate modifies aberrant subchondral bone remodeling and reduces innervation and pain behavior at the early stage of OA. These results suggest that intervention of the axonal guidance molecules (e.g., netrin-1) derived from aberrant subchondral bone remodeling may have therapeutic potential for OA pain.

Electrical conductivity (EC) in aerosols, snow, and meltwater were evaluated at the headwater of the Urumqi River during the ablation seasons of 2003–2008. The results show that EC in meltwater can indicate the intensity of glacier ablation, which negatively correlated with air temperature and discharge. During the early ablation period, EC presents a fluctuation trend and runoff may be primarily from snow, frozen soil, and groundwater. EC decreases to the lowest level during the peak-flow period and runoff flows rapidly through a hydrological system predominantly in ice-walled conduits. EC increases to the highest level during the late ablation period, and runoff transports slowly through a distributed hydrological system at the ice-rock interface. EC in meltwater is far greater than in aerosols, surface snow, and precipitation, which are closely related to atmospheric circulation and dust loading. EC in snow pits denote the spatial variation of snow melting, the enrichment and loss of dissolved ions, and are affected by air temperature. The key ions to determine EC in meltwater are HCO3-, Ca2+ and SO42-, and its dominant control might be biogeochemical pyrite oxidation coupled with calcite and/or dolomite dissolution.

We assemble the most complete and clean red supergiant (RSG) sample (2,121 targets) so far in the Small Magellanic Cloud (SMC) with 53 different bands of data to study the MLR of RSGs. In order to match the observed spectral energy distributions (SEDs), a theoretical grid of 17,820 Oxygen-rich models (``normal'' and ``dusty'' grids are half-and-half) is created by the radiatively-driven wind model of the DUSTY code, covering a wide range of dust parameters. We select the best model for each target by calculating the minimal modified chi-square and visual inspection. The resulting MLRs from DUSTY are converted to real MLRs based on the scaling relation, for which a total MLR of \\(6.16\\times10^{-3}\\) \\(M_\\odot\\) yr\\(^{-1}\\) is measured (corresponding to a dust-production rate of \\(\\sim6\\times10^{-6}\\) \\(M_\\odot\\) yr\\(^{-1}\\)), with a typical MLR of \\(\\sim10^{-6}\\) \\(M_\\odot\\) yr\\(^{-1}\\) for the general population of the RSGs. The complexity of mass-loss estimation based on the SED is fully discussed for the first time, indicating large uncertainties based on the photometric data (potentially up to one order of magnitude or more). The Hertzsprung-Russell and luminosity versus median absolute deviation diagrams of the sample indicate the positive relation between luminosity and MLR. Meanwhile, the luminosity versus MLR diagrams show a ``knee-like'' shape with enhanced mass-loss occurring above \\(\\log_{10}(L/L_\\odot)\\approx4.6\\), which may be due to the degeneracy of luminosity, pulsation, low surface gravity, convection, and other factors. We derive our MLR relation by using a third-order polynomial to fit the sample and compare our result with previous empirical MLR prescriptions. Given that our MLR prescription is based on a much larger sample than previous determinations, it provides a more accurate relation at the cool and luminous region of the H-R diagram at low-metallicity compared to previous studies.