Fabrication of Rhenium Disulfide/Mesoporous Silica Core-Shell Nanoparticles for a pH-Responsive Drug Release and Combined Chemo-Photothermal Therapy.

A stimuli-responsive drug delivery nanocarrier with a core-shell structure combining photothermal therapy and chemotherapy for killing cancer cells was constructed in this study. The multifunctional nanocarrier ReS2@mSiO2-RhB entails an ReS2 hierarchical nanosphere coated with a fluorescent mesoporous silica shell. The three-dimensional hierarchical ReS2 nanostructure is capable of effectively absorbing near-infrared (NIR) light and converting it into heat. These ReS2 nanospheres were generated by a hydrothermal synthesis process leading to the self-assembly of few-layered ReS2 nanosheets. The mesoporous silica shell was further coated on the surface of the ReS2 nanospheres through a surfactant-templating sol-gel approach to provide accessible mesopores for drug uploading. A fluorescent dye (Rhodamine B) was covalently attached to silica precursors and incorporated during synthesis in the mesoporous silica walls toward conferring imaging capability to the nanocarrier. Doxorubicin (DOX), a known cancer drug, was used in a proof-of-concept study to assess the material's ability to function as a drug delivery carrier. While the silica pores are not capped, the drug molecule loading and release take advantage of the pH-governed electrostatic interactions between the drug and silica wall. The ReS2@mSiO2-RhB enabled a drug loading content as high as 19.83 mg/g doxorubicin. The ReS2@mSiO2-RhB-DOX nanocarrier's cumulative drug release rate at pH values that simulate physiological conditions showed significant pH responsiveness, reaching 59.8% at pH 6.8 and 98.5% and pH 5.5. The in vitro testing using HeLa cervical cancer cells proved that ReS2@mSiO2-RhB-DOX has a strong cancer eradication ability upon irradiation with an NIR laser owing to the combined drug delivery and photothermal effect. The results highlight the potential of ReS2@mSiO2-RhB nanoparticles for combined cancer therapy in the future.

Preoperative Anxiolytic and Sedative Effects of Intranasal Remimazolam and Dexmedetomidine: A Randomized Controlled Clinical Study in Children Undergoing General Surgeries.

Purpose: Remimazolam, an ultra-short-acting and fast-metabolized sedative, has only been sporadically investigated in children. This study was performed to determine the beneficial effects of intranasal remimazolam or dexmedetomidine on preoperative anxiety in children undergoing general surgeries. Patients and Methods: Ninety children were randomly and equally assigned to Group R (intranasal remimazolam 1.5mg kg-1), Group D (intranasal dexmedetomidine 2 mcg kg-1), and Group C (intranasal distilled water). The primary outcomes were the preoperative anxiety scores using the modified Yale preoperative anxiety scale (m-Ypas). The secondary outcomes included the cooperation behaviour of intranasal drug application, preoperative sedation levels, parental separation anxiety scores (PSAS), and mask acceptance scores (MAS). Results: Group R showed a significant low anxiety at 10 min after intranasal premedication (vs group C, P=0.010; vs group D, P = 0.002) and at anaesthesia induction (vs group C, P = 0.004). Group D showed a significantly low anxiety score only prior to anaesthesia induction (vs group C, P = 0.005). Most children in group R achieved mild sedation at 10 min (vs group C, P < 0.001; vs group D, P < 0.001), with a few progressing to deep sedation afterwards, while group D tended toward deep sedation. Compared to Group C, patients in Group R performed significantly better on the MAS (P = 0.014) and PSAS (P = 0.008). However, remimazolam did cause poor cooperation behavior to the intranasal application due to its mucosal irritation (vs group C, P = 0.001; vs group D, P = 0.010). Conclusion: Both intranasal remimazolam and dexmedetomidine can effectively alleviate preoperative anxiety in children. While intranasal remimazolam has a rapid onset, it produces only mild sedation and causes substantial nasal irritation. Trial Registration: NCT04720963, January 22, 2021, ClinicalTrials.Gov.

Leafhopper salivary carboxylesterase suppresses JA-Ile synthesis to facilitate initial arbovirus transmission in rice phloem.

Plant jasmonoyl-L-isoleucine (JA-Ile) is a major defense signal against insect feeding, but whether or how insect salivary effectors suppress JA-Ile synthesis and thus facilitate viral transmission in plant phloem remains elusive. Insect carboxylesterases (CarEs) are the third major family of detoxification enzymes. Here, we identify a new leafhopper CarE10 that specifically expressed in salivary glands and is secreted into rice phloem as the saliva component. Leafhopper CarE10 directly binds and promotes rice Jasmonate resistant 1 (JAR1) degradation by the proteasome system. Moreover, the direct association of CarE10 with JAR1 obviously impairs JAR1 enzyme activity for JA conversion to JA-Ile in in-vitro JA-Ile synthesis system. A devastating rice reovirus activates and promotes co-secretion of virions and CarE10 by virus-induced vesicles into saliva-stored salivary cavities of leafhopper vectors and ultimately into rice phloem to establish initial infection. Furthermore, virus-mediated increase of CarE10 secretion or overexpression of CarE10 in transgenic rice plants causes the reduced levels of JAR1 and thus suppresses JA-Ile synthesis, thereby promoting host attractiveness to insect vectors and facilitating initial viral transmission. Our findings provide insights into how insect salivary protein CarE10 suppresses host JA-Ile synthesis to benefit initial virus transmission in rice phloem.

Displacement-pressure biparametrically regulated softness sensory system for intraocular pressure monitoring.

High intraocular pressure (IOP) is one of the high-risk pathogenic factors of glaucoma. Existing methods of IOP measurement are based on the direct interaction with the cornea. Commercial ophthalmic tonometers based on snapshot measurements are expensive, bulky, and their operation requires trained personnel. Theranostic contact lenses are easy to use, but they may block vision and cause infection. Here, we report a sensory system for IOP assessment that uses a soft indentor with two asymmetrically deployed iontronic flexible pressure sensors to interact with the eyelid-eyeball in an eye-closed situation. Inspired by human fingertip assessment of softness, the sensory system extracts displacement-pressure information for soft evaluation, achieving high accuracy IOP monitoring (>96%). We further design and custom-make a portable and wearable ophthalmic tonometer based on the sensory system and demonstrate its high efficacy in IOP screening. This sensory system paves a way towards cost-effective, robust, and reliable IOP monitoring.

Sodium halide solid state electrolyte of Na3YBr6 with low activation energy.

Halide solid-state electrolytes (SSEs) are considered promising candidates for practical applications in all-solid-state batteries (ASSBs), due to their outstanding high voltage stability and compatibility with electrode materials. However, Na+ halide SSEs suffer from low ionic conductivity and high activation energy, which limit their applications in sodium all-solid-state batteries. Here, sodium yttrium bromide solid-state electrolytes (Na3YBr6) with a low activation energy of 0.15 eV is prepared via solid state reaction. Structure characterization using X-ray diffraction reveals a monoclinic structure (P21/c) of Na3YBr6. First principle calculations reveal that the low migration activation energy comes from the larger size and vibration of Br- anions, both of which expand the Na+ ion migration channel and reduce its activation energy. The electrochemical window of Na3YBr6 is determined to be 1.43 to 3.35 V vs. Na/Na+, which is slightly narrower than chlorides. This work indicates bromides are a good catholyte candidate for sodium all solid-state batteries, due to their low ion migration activation energy and relatively high oxidation stability.

Flexible SERS sensor based on the photodecoration of Au-NPs on Co3O4 NWs/carbon fiber cloth for the ultrasensitive detection of methylene blue in the curved fish surfaces.

BACKGROUND: Development of flexible platform via the surface-enhanced Raman spectroscopy (SERS) technique has gained enormous attention as a low-cost and portable substrate for a wide range application. In particular, the fabrication of semiconductors and tuning their surface morphologies with plasmonic nanoparticles are considered to be a fascinating strategy to create numerous hotspots to yield superior SERS enhancement. RESULTS: This work involved fabricating a flexible SERS active substrate using the carbon fiber cloth (CFC), which is hydrothermally grown with cobalt oxide nanowires (Co3O4 NWs) and photodecorated with plasmonic gold nanoparticles (Au-NPs) for the ultrasensitive detection of organic dye, methylene blue (MB). The proposed substrate exhibits high enhancement factor (4.5 × 1010), low limit of detection (1.42 × 10-10 M), good uniformity (6.27 %), superior reproducibility (6.30 %) and demonstrate an excellent mechanical strength up to 40 cycles towards the MB detection. The residues of the MB are directly detected on the fish surfaces by adopting a facile swab-sampling technique. Additionally, the proposed flexible SERS sensor exhibit a successful photodegradation of MB at 90 min under UVC light irradiation. SIGNIFICANCE AND NOVELTY: The proposed flexible SERS methodology for detecting MB in the curved surfaces exhibited a superior SERS enhancement owing to the synergistic effect raised from the Co3O4 NWs (chemical enhancement) and Au NPs (electromagnetic enhancement). These findings indicate that the CFC-based flexible SERS sensor is a promising candidate for detecting various organic pollutants in real-time and on non-planar surfaces.

Urinary non-albumin protein-creatinine ratio is an independent predictor of mortality in patients with type 2 diabetes: a retrospective cohort study.

Albuminuria is a well-known predictor of chronic kidney disease in patients with type 2 diabetes mellitus (DM). However, proteinuria is associated with chronic complications in patients without albuminuria. In this retrospective cohort study, we explored whether non-albumin proteinuria is associated with all-cause mortality and compared the effects of non-albumin proteinuria on all-cause mortality between patients with and without albuminuria. We retrospectively collected data from patients with type 2 DM for whom we had obtained measurements of both urinary albumin-to-creatinine ratio (UACR) and urinary protein-to-creatinine ratio (UPCR) from the same spot urine specimen. Urinary non-albumin protein-creatinine ratio (UNAPCR) was defined as UPCR-UACR. Of the 1809 enrolled subjects, 695 (38.4%) patients died over a median follow-up of 6.4 years. The cohort was separated into four subgroups according to UACR (30 mg/g) and UNAPCR (120 mg/g) to examine whether these indices are associated with all-cause mortality. Compared with the low UACR and low UNAPCR subgroup as the reference group, multivariable Cox regression analyses indicated no significant difference in mortality in the high UACR and low UNAPCR subgroup (hazard ratio [HR] 1.189, 95% confidence interval [CI] 0.889-1.589, P = 0.243), but mortality risks were significantly higher in the low UACR and high UNAPCR subgroup (HR 2.204, 95% CI 1.448-3.356, P < 0.001) and in the high UACR with high UNAPCR subgroup (HR 1.796, 95% CI 1.451-2.221, P < 0.001). In the multivariable Cox regression model with inclusion of both UACR and UNAPCR, UNAPCR ≥ 120 mg/g was significantly associated with an increased mortality risk (HR 1.655, 95% CI 1.324-2.070, P < 0.001), but UACR ≥ 30 mg/g was not significantly associated with mortality risk (HR 1.046, 95% CI 0.820-1.334, P = 0.717). In conclusion, UNAPCR is an independent predictor of all-cause mortality in patients with type 2 DM.

A keratinocyte-adipocyte signaling loop is reprogrammed by loss of BTG3 to augment skin carcinogenesis.

Obesity is endemic to many developed countries. Overweight or obesity is associated with an increased risk of developing cancer. Dysfunctional adipose tissue alters cancer cell proliferation and migration; however, whether and how neoplastic epithelial cells communicate with adipose tissue and the underlying mechanism are less clear. BTG3 is a member of the anti-proliferative BTG/Tob family and functions as a tumor suppressor. Here, we demonstrated that BTG3 levels are downregulated in basal cell carcinoma and squamous cell carcinoma compared to normal skin tissue, and Btg3 knockout in mice augmented the development of papilloma in a mouse model of DMBA/TPA-induced skin carcinogenesis. Mechanistically, BTG3-knockout keratinocytes promoted adipocyte differentiation mainly through the release of IL1α, IL10, and CCL4, as a result of elevated NF-κB activity. These adipocytes produced CCL20 and FGF7 in a feedback loop to promote keratinocyte migration. Thus, our findings showcased the role of BTG3 in guarding the interplay between keratinocytes and adjacent adipocytes, and identified the underlying neoplastic molecular mediators that may serve as possible targets in the treatment of skin cancer.

Miniaturized inkjet-printed flexible ion-selective sensing electrodes with the addition of graphene in PVC layer for fast response real-time monitoring applications.

In this letter, we propose a miniaturization scheme of inkjet printed ionic sensing electrodes by adding graphene into the ion-selective PVC film not only to reduce the impedance of the ionic liquid layer of the electrode but also to increase the electrode capacitance for the reduction of the response time. Based on the scheme, we present a fully inkjet-printed electrochemical ion-selective sensor comprising a working electrode and reference electrode, which are inkjet-printed Ag NPs/PEDOT:PSS-graphene/PVC-graphene and Ag/AgCl(s)/ionic liquid PVC-graphene layer structures, respectively. The printed ion-selective working electrode has been miniaturized to a size of 22,400 µm2 equivalent to a square shape of ∼150 × 150 µm2 comparable to the size of a human cell. By adding graphene to the ion selective PVC film, more than 90 % charge transfer resistance reduction can be achieved and the shunt capacitance is increased by 3.4-fold in shunt capacitance compared to the film without graphene, thereby more than 33 % reduction of the response time required to reach equilibrium. Meanwhile, these miniaturized potassium sensors using the working electrodes with/without adding graphene have been integrated with in-lab signal-processing and wireless-transmission module to yield similar results to the one measured by commercial electrochemical workstation showing a great potential for real-time monitoring in portable clinical trials. Specifically, the proposed sensor utilizing graphene-enhanced electrodes demonstrates a linearity uncertainty of 2.9 mV, which is approximately half of the uncertainty observed in the sensors lacking graphene integration.

Comparative Analysis of Out-of-Hospital Cardiac Arrest Outcomes in Health Clinics, Nursing Homes, and Public Places: Implications for Optimizing Automated External Defibrillator Strategies.

Purpose: Various factors, such as event location and response time, influence the outcomes of out-of-hospital cardiac arrest (OHCA). Very few studies have explored the delivery of basic life support (BLS) to patients having OHCA at health clinics or nursing homes-settings with professional BLS providers. Thus, in this study, we compared prognostic and survival outcomes between health clinics, nursing homes, and other public places (eg, workplaces and sports facilities/recreational areas) to offer insights for optimizing OHCA outcomes. Patients: This study included adults who had nontraumatic OHCA in Taoyuan City between January 2017 and December 2022. Methods: We collected data on patient characteristics, emergency medical service parameters, onsite patient management, automated external defibrillator (AED) locations, OHCA prognosis, and survival outcomes. Multivariate analyses were performed to predict survival to discharge (primary outcome) and neurological outcomes at discharge (secondary outcome). Results: During the study period, the numbers of OHCA events at health clinics, nursing homes, and other public places were 158, 208, and 1986, respectively. The mean age of OHCA in health medical clinics, nursing home and other public places were 63.4, 81.5 and 64.7, respectively (P value<0.001). The proportion of witnessed events, rate of bystander resuscitation, and frequency of AED utilization were the highest for health clinics (53.2% (84/158), 83.4% (132/158), and 13.3% (21/158), respectively, P value<0.001). The average AED-scene distances and response times were the lowest for health clinics (388.8 m and 5.4 min, respectively). In initial shockable rhythm group, the probabilities of survival to discharge at discharge were the highest for health clinics (aOR=1.41, 95% CI=1.04-1.81, P value=0.041)) and lowest for nursing homes (aOR=0.84, 95% CI=0.76-0.93, P value=0.024). Conclusion: Our research shows that OHCA patients at medical health clinics have higher rates of witnessing and bystander CPR and AED usage than other public places. However, while survival rates for patients with shockable rhythms are slightly better at health clinics, the neurological outcomes are not significantly different. The AED-scene distances are too far to be used effectively.

Catalytically Relevant Organocopper(III) Complexes Formed through Aryl-Radical-Enabled Oxidative Addition.

Stepwise oxidative addition of copper(I) complexes to form copper(III) species via single electron transfer (SET) events has been widely proposed in copper catalysis. However, direct observation and detailed investigation of these fundamental steps remain elusive owing largely to the typically slow oxidative addition rate of copper(I) complexes and the instability of the copper(III) species. We report herein a novel aryl-radical-enabled stepwise oxidative addition pathway that allows for the formation of well-defined alkyl-CuIII species from CuI complexes. The process is enabled by the SET from a CuI species to an aryl diazonium salt to form a CuII species and an aryl radical. Subsequent iodine abstraction from an alkyl iodide by the aryl radical affords an alkyl radical, which then reacts with the CuII species to form the alkyl-CuIII complex. The structure of resultant [(bpy)CuIII(CF3)2(alkyl)] complexes has been characterized by NMR spectroscopy and X-ray crystallography. Competition experiments have revealed that the rate at which different alkyl iodides undergo oxidative addition is consistent with the rate of iodine abstraction by carbon-centered radicals. The CuII intermediate formed during the SET process has been identified as a four-coordinate complex, [CuII(CH3CN)2(CF3)2], through electronic paramagnetic resonance (EPR) studies. The catalytic relevance of the high-valent organo-CuIII has been demonstrated by the C-C bond-forming reductive elimination reactivity. Finally, localized orbital bonding analysis of these formal CuIII complexes indicates inverted ligand fields in σ(Cu-CH2) bonds. These results demonstrate the stepwise oxidative addition in copper catalysis and provide a general strategy to investigate the elusive formal CuIII complexes.

Arthroscopic debridement, synovectomy and thermal shrinkage for basal joint arthritis.

BACKGROUND: Ligamentous laxity, cartilage wear, and diffuse synovitis are frequently seen in thumb basal joint arthritis. Although these degenerative changes may be mild for the majority, they have the potential to cause discomfort during movement and compromised hand function. This study assesses the long-term outcomes of arthroscopic debridement, synovectomy, and thermal shrinkage in managing early-stage basal joint arthritis. METHODS: We retrospectively reviewed patients with basal joint arthritis who underwent arthroscopic debridement, synovectomy, and thermal shrinkage between November 2010 and January 2021 by a single surgeon at our medical institute. We assessed functional outcomes, thumb range of motion, perioperative nonsteroidal anti-inflammatory drug (NSAID) use, return to work and satisfaction level. RESULTS: A total of 12 patients (13 hands), with a mean follow-up of 72 months, were included in this study. Significant improvements were observed in pain scores and functional outcomes, along with a reduction in postoperative NSAID use. Patients also reported a relatively quick return to work and a high satisfaction level. CONCLUSION: The study highlights the benefits of arthroscopic intervention, providing a minimally invasive approach with favorable long-term outcomes for patients with symptomatic basal joint arthritis.

A phytoplasma effector destabilizes chloroplastic glutamine synthetase inducing chlorotic leaves that attract leafhopper vectors.

Leaf yellowing is a well-known phenotype that attracts phloem-feeding insects. However, it remains unclear how insect-vectored plant pathogens induce host leaf yellowing to facilitate their own transmission by insect vectors. Here, we report that an effector protein secreted by rice orange leaf phytoplasma (ROLP) inhibits chlorophyll biosynthesis and induces leaf yellowing to attract leafhopper vectors, thereby presumably promoting pathogen transmission. This effector, designated secreted ROLP protein 1 (SRP1), first secreted into rice phloem by ROLP, was subsequently translocated to chloroplasts by interacting with the chloroplastic glutamine synthetase (GS2). The direct interaction between SRP1 and GS2 disrupts the decamer formation of the GS2 holoenzyme, attenuating its enzymatic activity, thereby suppressing the synthesis of chlorophyll precursors glutamate and glutamine. Transgenic expression of SRP1 in rice plants decreased GS2 activity and chlorophyll precursor accumulation, finally inducing leaf yellowing. This process is correlated with the previous evidence that the knockout of GS2 expression in rice plants causes a similar yellow chlorosis phenotype. Consistently, these yellowing leaves attracted higher numbers of leafhopper vectors, caused the vectors to probe more frequently, and presumably facilitate more efficient phytoplasma transmission. Together, these results uncover the mechanism used by phytoplasmas to manipulate the leaf color of infected plants for the purpose of enhancing attractiveness to insect vectors.

PRDX1 Interfering Peptide Disrupts Amino Acids 70-90 of PRDX1 to Inhibit the TLR4/NF-κB Signaling Pathway and Attenuate Neuroinflammation and Ischemic Brain Injury.

Ischemic stroke ranks among the leading causes of death and disability in humans and is accompanied by motor and cognitive impairment. However, the precise mechanisms underlying injury after stroke and effective treatment strategies require further investigation. Peroxiredoxin-1 (PRDX1) triggers an extensive inflammatory cascade that plays a pivotal role in the pathology of ischemic stroke, resulting in severe brain damage from activated microglia. In the present study, we used molecular dynamics simulation and nuclear magnetic resonance to detect the interaction between PRDX1 and a specific interfering peptide. We used behavioral, morphological, and molecular experimental methods to demonstrate the effect of PRDX1-peptide on cerebral ischemia-reperfusion (I/R) in mice and to investigate the related mechanism. We found that PRDX1-peptide bound specifically to PRDX1 and improved motor and cognitive functions in I/R mice. In addition, pretreatment with PRDX1-peptide reduced the infarct area and decreased the number of apoptotic cells in the penumbra. Furthermore, PRDX1-peptide inhibited microglial activation and downregulated proinflammatory cytokines including IL-1ß, IL-6, and TNF-α through inhibition of the TLR4/NF-κB signaling pathway, thereby attenuating ischemic brain injury. Our findings clarify the precise mechanism underlying PRDX1-induced inflammation after ischemic stroke and suggest that the PRDX1-peptide can significantly alleviate the postischemic inflammatory response by interfering with PRDX1 amino acids 70-90 and thereby inhibiting the TLR4/NF-κB signaling pathway. Our study provides a theoretical basis for a new therapeutic strategy to treat ischemic stroke.

Machine learning-based longitudinal prediction for GJB2-related sensorineural hearing loss.

BACKGROUND: Recessive GJB2 variants, the most common genetic cause of hearing loss, may contribute to progressive sensorineural hearing loss (SNHL). The aim of this study is to build a realistic predictive model for GJB2-related SNHL using machine learning to enable personalized medical planning for timely intervention. METHOD: Patients with SNHL with confirmed biallelic GJB2 variants in a nationwide cohort between 2005 and 2022 were included. Different data preprocessing protocols and computational algorithms were combined to construct a prediction model. We randomly divided the dataset into training, validation, and test sets at a ratio of 72:8:20, and repeated this process ten times to obtain an average result. The performance of the models was evaluated using the mean absolute error (MAE), which refers to the discrepancy between the predicted and actual hearing thresholds. RESULTS: We enrolled 449 patients with 2184 audiograms available for deep learning analysis. SNHL progression was identified in all models and was independent of age, sex, and genotype. The average hearing progression rate was 0.61 dB HL per year. The best MAE for linear regression, multilayer perceptron, long short-term memory, and attention model were 4.42, 4.38, 4.34, and 4.76 dB HL, respectively. The long short-term memory model performed best with an average MAE of 4.34 dB HL and acceptable accuracy for up to 4 years. CONCLUSIONS: We have developed a prognostic model that uses machine learning to approximate realistic hearing progression in GJB2-related SNHL, allowing for the design of individualized medical plans, such as recommending the optimal follow-up interval for this population.

Age-dependent distribution of IgA and IgG antibody-secreting cells in the pharyngeal tonsil of the Bactrian camel.

The pharyngeal tonsil, located in the nasopharynx, can effectively defend against pathogens invading the body from the upper respiratory tract and play a crucial role in mucosal immunity of the respiratory tract. Immunoglobulin A (IgA) and Immunoglobulin G (IgG) serve as key effector molecules in mucosal immunity, exhibiting multiple immune functions. This study aimed to investigate the distribution patterns and age-related alterations of IgA and IgG antibody-secreting cells (ASCs) in the pharyngeal tonsils of Bactrian camels. Twelve Alashan Bactrian camels were categorized into four age groups: young (1-2 years, n=3), pubertal (3-5 years, n=3), middle-aged (6-16 years, n=3) and old (17-20 years, n=3). The distribution patterns of IgA and IgG ASCs in the pharyngeal tonsils of Bactrian camels of different ages were meticulously observed, analyzed and compared using immunohistochemical and statistical methods. The results revealed that IgA ASCs in the pharyngeal tonsils of all age groups were primarily clustered or diffusely distributed in the reticular epithelium and its subepithelial regions (region A) and around the glands (region C), scattered in the subepithelial regions of non-reticular epithelium (region B), and sporadically distributed in the interfollicular regions (region D). Interestingly, the distribution pattern of IgG ASCs in the pharyngeal tonsils closely mirrored that of IgA ASCs. The distribution densities of IgA and IgG ASCs in these four regions were significantly decreased in turn (P<0.05). However, IgA ASCs exhibited significantly higher densities than IgG ASCs in the same region (P<0.05). Age-related alterations indicated that the distribution densities of IgA and IgG ASCs in each region of the pharyngeal tonsils exhibited a trend of initially increasing and subsequently decreasing from young to old camels, reaching a peak in the pubertal group. As camels age, there was a significant decrease in the densities of IgA and IgG ASCs in all regions of the pharyngeal tonsils (P<0.05). The results demonstrate that the reticular epithelium and its subepithelial regions in the pharyngeal tonsils of Bactrian camels are the primary regions where IgA and IgG ASCs colonize and exert their immune functions. These regions play a pivotal role in inducing immune responses and defending against pathogen invasions in the pharyngeal tonsils. IgA ASCs may be the principal effector cells of the mucosal immune response in the pharyngeal tonsils of Bactrian camels. Aging significantly reduces the densities of IgA and IgG ASCs, while leaving their distribution patterns unaffected. These findings will provide valuable insights for further investigations into the immunomorphology, immunosenescence, and response mechanisms of the pharyngeal tonsils in Bactrian camels.

Novel CRTC1::MRTFB(MKL2) Gene Fusion detected in Myxoid Mesenchymal Neoplasms with Myogenic Differentiation involving Bone and Soft Tissue.

Appropriate classification of fusion-driven bone and soft tissue neoplasms continues to evolve, often relying on the careful integration of morphologic findings with immunohistochemical, molecular, and clinical data. Herein, we present three cases of a morphologically distinct myxoid mesenchymal neoplasm with myogenic differentiation and novel CRTC1::MRTFB (formerly MKL2) gene fusion. Three tumors occurred in 2 female and 1 male patient with a median age of 72 (range: 28-78). Tumors involved the left iliac bone, the right thigh, and the left perianal region with a median size of 4.0 cm (4.0-7.6 cm). While one tumor presented as an incidental finding, the other two tumors were noted given their persistent growth. At the time of last follow-up, one patient was alive with unresected disease at 6 months, one patient was alive without evidence of disease at 12 months after surgery and one patient died of disease 24 months after diagnosis. On histologic sections, the tumors showed multinodular growth and were composed of variably cellular spindle to round-shaped cells with distinct brightly eosinophilic cytoplasm embedded within a myxoid stroma. One tumor showed overt smooth muscle differentiation. Cytologic atypia and mitotic activity ranged from minimal (2 cases) to high (1 case). By immunohistochemistry, the neoplastic cells expressed focal smooth muscle actin, h-caldesmon, and desmin in all tested cases. Skeletal muscle markers were negative. Next-generation sequencing detected nearly identical CRTC1::MRTFB gene fusions in all cases. We suggest that myxoid mesenchymal tumors with myogenic differentiation harboring a CRTC1::MRTFB fusion may represent a previously unrecognized, distinctive entity that involves soft tissue and bone. Continued identification of these novel myxoid neoplasms with myogenic differentiation will be important in determining appropriate classification, understanding biologic potential, and creating treatment paradigms.

Pain prediction model based on machine learning and SHAP values for elders with dementia in Taiwan.

INTRODUCTION: Pain conditions are common in elderly individuals, including those with dementia. However, symptoms associated with dementia may lead to poor recognition, assessment and management of pain. In this study, we incorporated the variables based on questionnaires into a machine learning algorithm to build a prediction model for the pain index of elderly individuals with dementia. MATERIALS AND METHODS: In this study, 113 cases were collected through questionnaires and used to build prediction models for the patient's pain index. Three machine learning algorithms were incorporated for comparison in this study. To interpret the prediction model, SHapley additive explanations values were used to depict the ranking importance of variables and the relationship between features and pain index. RESULTS: In the comparison of models, random forests with feature selection outperformed in terms of root mean square error and mean absolute error. A total of 11 features were selected based on embedded method. The results showed that the Karnofsky scale played a key role in predicting pain index for elderly individuals with dementia and was positively associated with pain index. Arthritis is the most important disease to predicting the pain index. CONCLUSIONS: Our findings provided the key insights to predict the pain index of elderly patients with dementia. In the future, it can be used to develop an application system or webpage, which can reduce the use of labour and improve the efficiency.

Improvement of biotic nitrate reduction in constructed photoautotrophic biofilm-soil microbial fuel cells.

The biotic nitrate reduction rate in freshwater ecosystems is typically constrained by the scarcity of carbon sources. In this study, 'two-chambers' - 'two-electrodes' photoautotrophic biofilm-soil microbial fuel cells (P-SMFC) was developed to accelerate nitrate reduction by activating in situ electron donors that originated from the soil organic carbon (SOC). The nitrate reduction rate of P-SMFC (0.1341 d-1) improved by âˆ¼ 1.6 times on the 28th day compared to the control photoautotrophic biofilm. The relative abundance of electroactive bacterium increased in the P-SMFC and this bacterium contributed to obtain electrons from SOC. Biochar amendment decreased the resistivity of P-SMFC, increased the electron transferring efficiency, and mitigated anodic acidification, which continuously facilitated the thriving of putative electroactive bacterium and promoted current generation. The results from physiological and ecological tests revealed that the cathodic photoautotrophic biofilm produced more extracellular protein, increased the relative abundance of Lachnospiraceae, Magnetospirillaceae, Pseudomonadaceae, and Sphingomonadaceae, and improved the activity of nitrate reductase and ATPase. Correspondingly, P-SMFC in the presence of biochar achieved the highest reaction rate constant for nitrate reduction (kobs) (0.2092 d-1) which was 2.4 times higher than the control photoautotrophic biofilm. This study provided a new strategy to vitalize in situ carbon sources in paddy soil for nitrate reduction by the construction of P-SMFC.

Diatomite-incorporated hierarchical scaffolds for osteochondral regeneration.

Osteochondral regeneration involves the highly challenging and complex reconstruction of cartilage and subchondral bone. Silicon (Si) ions play a crucial role in bone development. Current research on Si ions mainly focuses on bone repair, by using silicate bioceramics with complex ion compositions. However, it is unclear whether the Si ions have important effect on cartilage regeneration. Developing a scaffold that solely releases Si ions to simultaneously promote subchondral bone repair and stimulate cartilage regeneration is critically important. Diatomite (DE) is a natural diatomaceous sediment that can stably release Si ions, known for its abundant availability, low cost, and environmental friendliness. Herein, a hierarchical osteochondral repair scaffold is uniquely designed by incorporating gradient DE into GelMA hydrogel. The adding DE microparticles provides a specific Si source for controlled Si ions release, which not only promotes osteogenic differentiation of rBMSCs (rabbit bone marrow mesenchymal stem cells) but also enhances proliferation and maturation of chondrocytes. Moreover, DE-incorporated hierarchical scaffolds significantly promoted the regeneration of cartilage and subchondral bone. The study suggests the significant role of Si ions in promoting cartilage regeneration and solidifies their foundational role in enhancing bone repair. Furthermore, it offers an economic and eco-friendly strategy for developing high value-added osteochondral regenerative bioscaffolds from low-value ocean natural materials.