Production of doubly charmed hadron Ξcc++\Xi_{cc}^{++} and Tcc+T_{cc}^+ in relativistic heavy ion collisions

Heavy ion collisions provide a unique opportunity for studying the properties of exotic hadrons with two charm quarks. The production of $T_{cc}^+$ is significantly enhanced in nuclear collisions compared to proton-proton collisions due to the creation of multiple charm pairs. In this study, we employ the Langevin equation in combination with the Instantaneous Coalescence Model (LICM) to investigate the production of $T_{cc}^+$ and $\Xi_{cc}^{++}$ which consists of two charm quarks. We consider $T_{cc}^+$ as molecular states composed of $D$ and $D^*$ mesons. The Langevin equation is used to calculate the energy loss of charm quarks and $D$ mesons in the hot medium. The hadronization process, where charm quarks transform into each $D$ state as constituents of $T_{cc}^+$ production, is described using the coalescence model. The coalescence probability between $D$ and $D^*$ is determined by the Wigner function, which encodes the information of the $T_{cc}^+$ wave function. Our results show that the $T_{cc}^+$ production varies by approximately one order of magnitude when different widths in the Wigner function, representing distinct binding energies of $T_{cc}^+$, are considered. This variation offers valuable insights into the nature of $T_{cc}^+$ through the analysis of its wave function. The $\Xi_{cc}^{++}$ is treated as a hadronic state produced at the hadronization of the deconfined matter. Its production is also calculated as a comparison with the molecular state $T_{cc}^+$.Comment: 7 pages, 5 figure

Curcumin-Loaded Mixed Micelles: Preparation, Characterization, and In Vitro

The objective of this study was to prepare curcumin-loaded mixed Soluplus/TPGS micelles (Cur-TPGS-PMs) for oral administration. The Cur-TPGS-PMs showed a mean size of 65.54 ± 2.57 nm, drug encapsulation efficiency over 85%, and drug loading of 8.17%. The Cur-TPGS-PMs were found to be stable in various pH media (pH 1.2 for 2 h, pH 6.8 for 2 h, and pH 7.4 for 6 h). The X-ray diffraction (XRD) patterns illustrated that curcumin was in the amorphous or molecular state within PMs. The In vitro release test indicated that Cur-TPGS-PMs possessed a significant sustained-release property. The cell viability in MCF-7 cells was found to be relatively lower in Cur-TPGS-PM-treated cells as compared to free Cur-treated cells. CLSM imaging revealed that mixed micelles were efficiently absorbed into the cytoplasm region of MCF-7 cells. Therefore, Cur-TPGS-PMs could have the significant value for the chronic breast cancer therapy

Rapamycin directly activates lysosomal mucolipin TRP channels independent of mTOR

Rapamycin (Rap) and its derivatives, called rapalogs, are being explored in clinical trials targeting cancer and neurodegeneration. The underlying mechanisms of Rap actions, however, are not well understood. Mechanistic target of rapamycin (mTOR), a lysosomelocalized protein kinase that acts as a critical regulator of cellular growth, is believed to mediate most Rap actions. Here, we identified mucolipin 1 (transient receptor potential channel mucolipin 1 [TRPML1], also known as MCOLN1), the principle Ca2+ release channel in the lysosome, as another direct target of Rap. Patch-clamping of isolated lysosomal membranes showed that micromolar concentrations of Rap and some rapalogs activated lysosomal TRPML1 directly and specifically. Pharmacological inhibition or genetic inactivation of mTOR failed to mimic the Rap effect. In vitro binding assays revealed that Rap bound directly to purified TRPML1 proteins with a micromolar affinity. In both healthy and disease human fibroblasts, Rap and rapalogs induced autophagic flux via nuclear translocation of transcription factor EB (TFEB). However, such effects were abolished in TRPML1-deficient cells or by TRPML1 inhibitors. Hence, Rap and rapalogs promote autophagy via a TRPML1-dependent mechanism. Given the demonstrated roles of TRPML1 and TFEB in cellular clearance, we propose that lysosomal TRPML1 may contribute a significant portion to the in vivo neuroprotective and anti-aging effects of Rap via an augmentation of autophagy and lysosomal biogenesis

Acupotomy Therapy for Chronic Nonspecific Neck Pain: A Systematic Review and Meta-Analysis

Objective. This review is to assess the efficacy and safety of acupotomy therapy in chronic nonspecific neck pain. Methods. We searched six computerised databases. Randomized controlled trials incorporating acupotomy therapy alone or combined with other conventional treatments for chronic nonspecific neck pain were included. Two reviewers screened each literature and extracted data independently according to Cochrane Reviews’ Handbook (5.1). The Cochrane Collaboration’s RevMan 5.3 software was applied for meta-analysis. Results. A total of ten trials involving 433 patients were enrolled. The pooled analysis indicated that acupotomy therapy showed a significant improving short-term and long-term effect on effective rate and cure rate. Meta-analysis demonstrated that acupotomy therapy group was superior to control group in restoring cervical lordosis and debasing VAS score. The result of continuous data did not support statistical significance of acupotomy therapy in adjusting clinical symptom score. For adverse events, acupotomy group did not reveal obvious superiority compared to control group. Conclusions. Acupotomy therapy may be beneficial to chronic nonspecific neck pain patients. To strengthen supportive evidence, future, more rigorously designed clinical trials, adequate adverse events, and follow-up project are recommended

Anticonvulsant activities of α-asaronol ((E)-3'-hydroxyasarone), an active constituent derived from α-asarone.

BACKGROUND: Epilepsy is one of chronic neurological disorders that affects 0.5-1.0% of the world's population during their lifetime. There is a still significant need to develop novel anticonvulsant drugs that possess superior efficacy, broad spectrum of activities and good safety profile. METHODS: α-Asaronol and two current antiseizure drugs (α-asarone and carbamazepine (CBZ)) were assessed by in vivo anticonvulsant screening with the three most employed standard animal seizure models, including maximal electroshock seizure (MES), subcutaneous injection-pentylenetetrazole (PTZ)-induced seizures and 3-mercaptopropionic acid (3-MP)-induced seizures in mice. Considering drug safety evaluation, acute neurotoxicity was assessed with minimal motor impairment screening determined in the rotarod test, and acute toxicity was also detected in mice. RESULTS: In our results, α-asaronol displayed a broad spectrum of anticonvulsant activity (ACA) and showed better protective indexes (PI = 11.11 in MES, PI = 8.68 in PTZ) and lower acute toxicity (LD50 = 2940 mg/kg) than its metabolic parent compound (α-asarone). Additionally, α-asaronol displayed a prominent anticonvulsant profile with ED50 values of 62.02 mg/kg in the MES and 79.45 mg/kg in the sc-PTZ screen as compared with stiripentol of ED50 of 240 mg/kg and 115 mg/kg in the relevant test, respectively. CONCLUSION: The results of the present study revealed α-asaronol can be developed as a novel molecular in the search for safer and efficient anticonvulsants having neuroprotective effects as well as low toxicity. Meanwhile, the results also suggested that α-asaronol has great potential to develop into another new aromatic allylic alcohols type anticonvulsant drug for add-on therapy of Dravet's syndrome

Endovascular Recanalization of Non-acute Symptomatic Middle Cerebral Artery Total Occlusion and Its Short-Term Outcomes

Background and Purpose: The optimal treatment for patients with non-acute symptomatic middle cerebral artery (MCA) total occlusion and a high risk of recurrent ischemic stroke despite medical management is not well-established. We aimed to assess the feasibility, safety, and short-term outcomes of angioplasty and stenting for these patients.Methods: Data of 22 patients with non-acute symptomatic MCA total occlusion who have failed medical management and undergone endovascular recanalization were retrospectively collected in our prospective database. All occlusive lesions were predilated with conventional balloons, followed by paclitaxel-coated coronary balloon inflation or not, and then a remedial stenting was performed or not, depending on the discretion of the operator. The rate of successful recanalization, perioperative outcomes, and short-term outcomes, such as restenosis and stroke recurrence, was analyzed.Results: Successful recanalization was achieved in 95.5% of patients, with 14 patients undergoing balloon angioplasty and 7 patients undergoing remedial stenting. Seven patients developed perioperative complications, including one patient with persistent neurological deficit. Over a median clinical follow-up duration of 5.0 months, only one patient had recurrent ischemic symptoms attributed to the cessation of antiplatelet treatment owing to postoperative intracranial hemorrhage. The proportion of patients who achieved favorable clinical outcome (modified ranking scale score of 0–2) was 85.7%. Post-procedural repeat vascular imaging was performed at 4.5 ± 1.84 months, with nine and one patient undergoing cerebral angiography and magnetic resonance angiography, respectively. One (10%) artery presented with asymptomatic reocclusion.Conclusions: Angioplasty and stenting may be feasible for the patients with non-acute symptomatic atherosclerotic MCA total occlusive disease who have failed medical management

A novel assay based on DNA melting temperature for multiplexed identification of SARS-CoV-2 and influenza A/B viruses

IntroductionThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and influenza viruses can cause respiratory illnesses with similar clinical symptoms, making their differential diagnoses challenging. Additionally, in critically ill SARS-CoV-2–infected patients, co-infections with other respiratory pathogens can lead to severe cytokine storm and serious complications. Therefore, a method for simultaneous detection of SARS-CoV-2 and influenza A and B viruses will be clinically beneficial.MethodsWe designed an assay to detect five gene targets simultaneously via asymmetric PCR-mediated melting curve analysis in a single tube. We used specific probes that hybridize to corresponding single-stranded amplicons at low temperature and dissociate at high temperature, creating different detection peaks representing the targets. The entire reaction was conducted in a closed tube, which minimizes the risk of contamination. The limit of detection, specificity, precision, and accuracy were determined.ResultsThe assay exhibited a limit of detection of <20 copies/μL for SARS-CoV-2 and influenza A and <30 copies/μL for influenza B, with high reliability as demonstrated by a coefficient of variation for melting temperature of <1.16% across three virus concentrations. The performance of our developed assay and the pre-determined assay showed excellent agreement for clinical samples, with kappa coefficients ranging from 0.98 (for influenza A) to 1.00 (for SARS-CoV-2 and influenza B). No false-positive, and no cross-reactivity was observed with six common non-influenza respiratory viruses.ConclusionThe newly developed assay offers a straightforward, cost-effective and nucleic acid contamination-free approach for simultaneous detection of the SARS-CoV-2, influenza A, and influenza B viruses. The method offers high analytical sensitivity, reliability, specificity, and accuracy. Its use will streamline testing for co-infections, increase testing throughput, and improve laboratory efficacy

Safety and efficacy of endovascular recanalization for symptomatic non-acute atherosclerotic intracranial large artery occlusion

Background and objectiveThe optimal treatment for patients with symptomatic non-acute atherosclerotic intracranial large artery occlusion (ILAO) despite medical treatment is not well established. We aimed to assess the safety, efficacy, and feasibility of angioplasty and stenting for these patients.MethodsA total of 251 consecutive patients with symptomatic non-acute atherosclerotic ILAO treated with interventional recanalization were retrospectively collected in our center from March 2015 to August 2021. The rate of successful recanalization, perioperative complications, and follow-up outcomes were evaluated.ResultsSuccessful recanalization was achieved in 88.4% (222/251) of the patients. A total of 24 (24/251, 9.6%) symptomatic complications occurred among 251 procedures. In the 193 patients with clinical follow-up during 19.0 ± 14.7 months, 11 (11/193, 5.7%) patients developed ischemic stroke and four (4/193, 2.1%) patients developed transient ischemic attack (TIA). In the 106 patients with vascular imaging follow-up during 6.8 ± 6.6 months, seven (7/106, 6.6%) patients had restenosis and 10 (10/106, 9.4%) patients had reocclusion.ConclusionThis study suggests that interventional recanalization may be a feasible, basically safe, and an effective alternative in carefully selected patients with symptomatic non-acute atherosclerotic ILAO who have failed medical management

Convergence of resistance and evolutionary responses in Escherichia coli and Salmonella enterica co-inhabiting chicken farms in China

Sharing of genetic elements among different pathogens and commensals inhabiting same hosts and environments has significant implications for antimicrobial resistance (AMR), especially in settings with high antimicrobial exposure. We analysed 661 Escherichia coli and Salmonella enterica isolates collected within and across hosts and environments, in 10 Chinese chicken farms over 2.5 years using novel data-mining methods. Most isolates within same hosts possessed same clinically relevant AMR-carrying mobile genetic elements (plasmids: 70.6%, transposons: 78%), which also showed recent common evolution. Machine learning revealed known and novel AMR-associated mutations and genes underlying resistance to 28 antimicrobials and primarily associated with resistance in E. coli and susceptibility in S. enterica. Many were essential and affected same metabolic processes in both species, albeit with varying degrees of phylogenetic penetration. Multi-modal strategies are crucial to investigate the interplay of mobilome, resistance and metabolism in cohabiting bacteria, especially in ecological settings where community-driven resistance selection occurs