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Abstract Background Osteoporosis and its primary complication, fragility fractures, contribute to substantial global morbidity and mortality. Gaucher disease (GD) is caused by glucocerebrosidase (GBA1) deficiency, leading to skeletal complications. This study aimed to investigate the impact of the GBA1 gene on osteoporosis progression in GD patients and the specific populations. Methods We selected 8115 patients with osteoporosis (T-score ≤ − 2.5) and 55,942 healthy individuals (T-score > − 1) from a clinical database (N = 95,223). Monocytes from GD patients were evaluated in relation to endoplasmic reticulum (ER) stress, inflammasome activation, and osteoclastogenesis. An in vitro model of GD patient’s cells treated with adeno-associated virus 9 (AAV9)-GBA1 to assess GBA1 enzyme activity, chitotriosidase activity, ER stress, and osteoclast differentiation. Longitudinal dual-energy X-ray absorptiometry (DXA) data tracking bone density in patients with Gaucher disease (GD) undergoing enzyme replacement therapy (ERT) over an extended period. Results The GBA1 gene variant rs11264345 was significantly associated [P

Abstract Ligand-induced receptor dimerization or oligomerization is a widespread mechanism for ensuring communication specificity, safeguarding receptor activation, and facilitating amplification of signal transduction across the cellular membrane. However, cell-surface antigen-induced multimerization (dubbed AIM herein) has not yet been consciously leveraged in chimeric antigen receptor (CAR) engineering for enriching T cell-based therapies. We co-developed ciltacabtagene autoleucel (cilta-cel), whose CAR incorporates two B-cell maturation antigen (BCMA)-targeted nanobodies in tandem, for treating multiple myeloma. Here we elucidated a structural and functional model in which BCMA-induced cilta-cel CAR multimerization amplifies myeloma-targeted T cell-mediated cytotoxicity. Crystallographic analysis of BCMA–nanobody complexes revealed atomic details of antigen–antibody hetero-multimerization whilst analytical ultracentrifugation and small-angle X-ray scattering characterized interdependent BCMA apposition and CAR juxtaposition in solution. BCMA-induced nanobody CAR multimerization enhanced cytotoxicity, alongside elevated immune synapse formation and cytotoxicity-mediating cytokine release, towards myeloma-derived cells. Our results provide a framework for contemplating the AIM approach in designing next-generation CARs.

In recent 10 years, an integrated rice-crayfish farming (IRF) has been developing rapidly in the middle and lower reaches of the Yangtze River in China, and produced significant economic and ecological benefits. However, the IRF mode consumes a large amount of water and brought a great risk of water shortage. In Jianghan Plain, Hubei province, China, there are 4 IRF modes, referring to rotation of rice and crayfish (RRC), rice-crayfish symbiosis (RCS), year-round crayfish farming in paddy fields (YRC), and continuous operation of rice planting and crayfish farming (COR). This study selected the 4 IRF modes to calculate and compare the precipitation suitable degree (PSD) of 17 counties with larger scale of IRF. The results showed that, annual PSD for different IRF modes varied greatly for same county and among different counties, the annually averaged PSD was from 0.52 to 1.06 from the northern to southern Jianghan Plain. Annually averaged PSD from large to small was ranked as RCS>COR>RRC>YRC. The PSD values of IRF was different among different months, and the highly suitable period for PSD was from March to July, and the precipitation of each county (city) fully meet the water demand of rice growth and crayfish farming. In August thorogh November, the spatial distribution of PSD showed largely variation, and the monthly PSD was lower in the northern Plain, and slightly higher in the southern. From December to the next February, the PSD was obviously lower than other stages, even in the south of Jianghan Plain, with high risk of water deficit at the stage. According to the water demand regulation of the 4 IRF modes, the suitable IRF mode was RRC and YRC for the south, and RCS and COR for the north of Jianghan Plain in China. Considering long term negative affects for flooded paddy field, the paddy field used for RCS or COR mode should be changed to other farming system for 1 year or 2 years, such as IRF replaces with rice and wheat (oilseed rape) rotation for 1 year or 2 years after IRF was conducted for 5 years, so as to avoid exacerbating soil gleying.

The excessive pumping of fines in saturated roadbed surface layer, which is induced by the fluid-solid interaction under dynamic loads from high-speed train, is a special form of high-speed railway subgrade defect reported recently. This can deteriorate the interface between nonballasted track structure bottom layer and roadbed surface layer and therefore lead to associated contact variation with the moving of trains. According to the dynamic Biot’s equations known as u-p formulation and the vehicle-track coupling dynamics theory, a vertical vehicle-slab track-subgrade coupling vibration model is developed to investigate the aforementioned contact variation-induced dynamic behavior of the whole system considering the fluid-solid interaction. Dynamic measurements from a field case study are adopted to verify the computation model proposed. Based on the numerical model validated, the effects of three contact variation statuses (continuous contact, vibrating contact, and contact loss) on dynamic responses of track subsystem and subgrade subsystem, such as dynamic pore-water pressure, vertical accelerations, and dynamic displacements both in time and frequency domains, are investigated. Also, a sensitivity analysis involving rail speeds and lengths of contact loss zone is performed, and the critical length of contact loss zone is suggested.

This work proposes the first hot-polymer fiber Fabry–Perot interferometer (HPFFPI) anemometer for sensing airflow. The proposed HPFFPI is based on a single-mode fiber (SMF) endface that is attached to a UV-cured polymer to form an ultracompact fiber Fabry–Perot microcavity. The proposed polymer microcavity was heated using a low-cost chip resistor with a controllable dc driving power to achieve a desired polymer’s steady-state temperature (T) that exceeds the T of the surrounding environment. The polymer is highly sensitive to variations of T with high repeatability. When the hot polymer was cooled by the measured flowing air, the wavelength fringes of its optical spectra shifted. The HPFFPI anemometers have been experimentally evaluated for different cavity lengths and heating power values. Experimental results demonstrate that the proposed HPFFPI responses well in terms of airflow measurement. A high sensitivity of 1.139 nm/(m/s) and a good resolution of 0.0088 m/s over the 0~2.54 m/s range of airflow were achieved with a cavity length of 10 μm and a heating power of 0.402 W.

As the development of tight gas fields enters the stable production stage, condensate oil forms a complex oil--water emulsifying system under the action of bubble drainage agent, corrosion inhibitor, hydrate inhibitor, and other additives to increase and stabilize production, as well as the formation of particulate matter. A new demulsification and flocculation agent suitable for condensate emulsifying system is developed to make the system unstable and the oil beads coalesce. In this paper, a polyether--quaternary ammonium salt reverse demulsifier (PPA) was synthesized by grafting a cationic group onto a five-membered block polyether X-75. A new type of demulsification--flocculation agent (CQ) was obtained through the complex modification of PPA and inorganic coagulant polyaluminum ferric chloride. Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, and gel chromatograph were used to characterize the group and molecular structure. The reaction parameters were optimized by single-factor experiment and the response surface method, and the demulsification--flocculation mechanism was determined by zeta potential, interfacial tension, and fractal dimension. Results showed the PPA demulsifier has active groups (block polyether) and cationic groups (polyquaternary ammonium salt) at the oil--water interface at the same time and can play a synergistic role between them. Single-factor experiment and response surface optimization showed CQ concentration and temperature were key factors affecting the demulsification-- flocculation effect. When CQ concentration was 547 mg/L, settling temperature was 27.9°C and PPA accounted for 71%. After settling for 30 min, the oil content and the concentration of total suspended solids (TSS) in the water decreased to 21.26 and 7.0 mg/L, respectively, which met the water quality requirements of reinjection (oil content ≤ 30 mg/L, TSS concentration ≤ 15 mg/L). By neutralizing and displacing active substances at the oil--water interface and sweeping by net trapping, CQ can coagulate oil beads and suspended particles to form large flocs and realize the efficient separation of oil beads, suspended particles, and water. [ABSTRACT FROM AUTHOR]

Background/Aim: Gaucher disease (GD) is a rare lysosomal storage disorder that can involve the lungs and pulmonary vasculature. The long-term effects of GD on respiratory health remain unclear due to limited data on the natural history of this disease. We analyzed electronic health records for 11,004 patients with GD over 10-20 years to determine the incidence of pulmonary hypertension (PH), lung disease, and other respiratory comorbidities and better understand disease course to guide management. Patients and Methods: We conducted a retrospective cohort study using the TriNetX research database of 130 million international patients. The incidence of primary/secondary PH, pulmonary heart disease, interstitial/obstructive/restrictive lung disease, pulmonary hemorrhage, and pulmonary embolism was assessed in patients with GD from 2000-2020. Results: Incidence rates of all conditions assessed increased from 10 to 20 years of follow-up. Excess risk of PH, lung disease, and pulmonary hemorrhage was significantly higher in GD patients after 20 versus 10 years. Conclusion: Extended follow-up in GD is associated with substantially higher risks of PH, lung disease and other respiratory comorbidities, highlighting the need for close monitoring and early intervention to mitigate long-term pulmonary decline. Improved understanding of mechanisms driving respiratory deterioration can support the development of novel treatments to optimize outcomes in this population at high risk of pulmonary morbidity and mortality. [ABSTRACT FROM AUTHOR]

We incidentally observed a case of clear cell papillary renal cell carcinoma of an 81-year-old woman, presenting with intermittent left flank pain. It is a recently described rare renal parenchymal tumor. [ABSTRACT FROM AUTHOR]

Aims Angiomatoid fibrous histiocytoma (AFH) is histologically typified by nodules of histiocytoid spindle cells with pseudoangiomatoid spaces, fibrous pseudocapsules and lymphocytic cuffs. The principal goal was to expand the spectrum of AFHs through clinicopathological and molecular characterisation. Methods Thirteen AFHs, including 11 with confirmed hallmark translocation, were reappraised for classic features, reactive osteoclasts, mitoses and stromal, architectural and cytomorphological variations, with CD99, desmin and EMA stained in available cases. Results Seven male and six female patients ranged in age from 4 to 63 years (median, 13), including 4 older than 20 years. Tumours were located on the extremities (n=6), trunk (n=4) and scalp (n=3). Although fibrous pseudocapsules were observed in all cases, four showed solid histology without pseudoangiomatoid spaces and another one lacked peripheral lymphoid infiltrates. Nuclear pleomorphism was striking in two cases, moderate in seven and absent in four, with osteoclasts seen in two cases. In three AFHs with sclerotic matrix, one exhibited perivascular hyalinisation and nuclear palisading, reminiscent of a schwannoma. In three varyingly myxoid tumours, one closely resembled a myoepithelioma with prominent reticular arrangement of spindle cells in an abundant myxoid stroma. Besides EWSR1 gene rearrangement detected in four cases by fluorescence in situ hybridisation (FISH), EWSR1-CREB1 fusion was confirmed in nine cases, including a schwannoma-like AFH, and EWSR1-ATF1 fusion detected in a myoepithelioma-like AFH. Immunohistochemically, 56% of AFHs were positive for EMA, 78% for desmin and 100% for CD99. Conclusions Molecular testing is diagnostic of variant AFHs displaying diverse histomorphological alterations in the architectural patterns, cytomorphology and extracellular matrix. [ABSTRACT FROM AUTHOR]

Clear cell adenocarcinoma (CCA) in the urinary tract is a rare neoplasmmorphologically identical to the Müllerian counterpart. Clear cell adenocarcinoma is extremely rare in the upper urinary tract. We present a case with CCA of the renal pelvis. Microscopically, the tumor exhibited exophytic growth with predominantly tubulocystic structures, as well as solid and papillary patterns. The neoplastic cells were cuboidal with clear to pale eosinophilic cytoplasm and abundant intracellular and extracellular eosinophilic hyaline globules. By immunohistochemically, the tumor was labeled by cytokeratins and hepatocyte nuclear factor-1β. The patient was still alive without evidence of recurrence in the follow-up period of nineteen months after diagnosis. [ABSTRACT FROM AUTHOR]

We report a rare case of melanotic oncocytic metaplasia of the nasopharynx in a 63-year-old man, presenting as several black nodules up to several millimeters at the nasopharynx. It is a benign mimicker of malignant melanoma. [ABSTRACT FROM AUTHOR]