Assuming the Multiple Point Principle (MPP) as a new law of Nature, we considered the existence of the two degenerate vacua of the Universe: a) the first Electroweak (EW) vacuum at $v_1\approx 246$ GeV—“true vacuum”, and b) the second Planck scale “false vacuum” at $v_2 \sim 10^{18}$ GeV. In these vacua, we investigated different topological defects. The main aim of the paper is an investigation of the black-hole-hedgehogs configurations as defects of the false vacuum. In the framework of the $f(R)$ gravity, described by the Gravi-Weak unification model, we considered a black-hole solution, which corresponds to a “hedgehog”—global monopole, that has been “swallowed” by the black-hole with mass core $M_{BH}\sim 10^{18}$ GeV and radius $\delta\sim 10^{-21}$ GeV$^{-1}$. Considering the results of the hedgehog lattice theory in the framework of the $SU(2)$ Yang-Mills gauge-invariant theory with hedgehogs in the Wilson loops, we have used the critical value of temperature for the hedgehogs’ confinement phase ($T_c\sim 10^{18}$ GeV). This result gave us the possibility to conclude that the SM shows a new physics (with contributions of the $SU(2)$-triplet Higgs bosons) at the scale $\sim 10$ TeV. This theory predicts the stability of the EW-vacuum and the accuracy of the MPP.

Abstract: Role of gut microbiome in human health is becoming apparent. The major functional impact of gut microbiome is transmitted through the microbial metabolites that are produced in the gut and interact with host cells either in the local gut environment or get absorbed in the circulation to impact distant cells/organs. Short chain fatty acids (SCFAs) are the major microbial metabolites that are produced in the gut through fermentation of non-digestible fibers. SCFAs are known to function through various mechanism, however, their signaling through free-fatty acid receptor 2 and 3 (FFAR2/3; type of G-coupled protein receptors) is new therapeutic approach. FFAR2/3 are widely expression in diverse cell types in human and mice, and functions as sensors of SCFAs to change several physiological and cellular functions. FFAR2/3 modulates neurological signaling, energy metabolism, intestinal cellular homeostasis, immune response and hormone synthesis. FFAR2/3 functions through Gi and/or Gq signaling, that is mediated through specific structural features of SCFAs-FFAR2/3 bindings and modulating specific signaling pathway. In this review, we discussed the wide-spread expression and structural homologies between human and mice FFAR2/3, and their role in different human health conditions. This information can unlock opportunities to weigh the potential of FFAR2/3 as drug target to prevent human diseases.

A ganglion cyst is a benign fluid-filled sac that typically appears on the dorsal aspect of the wrist, arising idiopathically near the joint capsule or tendon sheath. Diagnosis is primarily clinical, with MRI and ultrasound serving as confirmation tools. Treatment options range from immobilization, aspiration, hydrossection, steroid or hyaluronidase injection, to surgical intervention. Although relatively uncommon, Dorsal Ganglion Cysts (DGC) can lead to Dorsal Wrist Impingement (DWI) syndrome. This syndrome results from the thickening of the wrist capsule due to overuse, injury, or repetitive activities. This thickening can lead to the compression of the extensor carpi radialis brevis (ECRB) tendon during wrist extension and produce tenderness around the lunate. In some refractory cases, MRI findings may show recurrent ganglion cysts, while in others, they may appear "normal." Consequently, the diagnosis remains clinical, and imaging is primarily employed to rule out secondary causes. Management strategies encompass rest, immobilization, occupational therapy, non-steroidal anti-inflammatory drugs (NSAIDs), cortisone injections, and, in certain instances, surgical intervention. Despite the clinical significance of these conditions, limited studies have explored their interrelationship. In this context, we present a rare case involving a 23-year-old female with recurrent DGC accompanied by DWI syndrome. Initially, the patient reported idiopathic left dorsal wrist pain localized around the tendon sheath. Her initial X-ray did not reveal any abnormalities, but MRI identified two ganglion cysts. A series of treatments were initiated, including left tendon sheath hydrossection, corticosteroid injections into the left wrist, and the excision of ganglion cysts from the left wrist. Furthermore, occupational therapy, oral Meloxicam, and Voltaren gel treatments were integrated into the management plan. Subsequent imaging confirmed the resolution of the cysts and an overall enhancement in the range of motion and wrist strength. However, the patient experienced only minimal pain relief, and pain was still elicited during end-range wrist extension and upon dorsal wrist palpation. An electromyography (EMG) test ordered to rule out neuropathic causes did not yield any conclusive results. Nonetheless, a repeat X-ray revealed mild soft tissue swelling on the dorsal side of the wrist, and a follow-up MRI detected ganglion cysts on the dorsal aspect of the lunate and the ECRB tendons. These findings indicated a re-accumulation of dorsal ganglion cysts with a concurrent dorsal impingement syndrome component. Consequently, the patient was referred to an orthopedic surgeon for evaluation and potential revision surgery. This unique case underscores the possibility of developing DWI Syndrome after the removal of a DGC. The diagnosis of this syndrome can be elusive, particularly when X-rays, MRIs, and EMGs yield negative results. Trauma, such as repeated hand surgery or recurrent ganglion cysts, may exacerbate wrist pain despite improvements in range of motion and strength. Special consideration should be given to patients who undergo surgical cyst excisions, as this procedure heightens the risk of recurrence and can irritate the tendon sheath. Collaborative efforts between Physical Medicine and Rehabilitation (PM&R), Occupational Therapy (OT), and surgical teams may play a pivotal role in managing pain associated with these conditions. We propose that future research endeavors should focus on establishing guidelines for the management of this unique condition.

Gut microbiota and its metabolites like short chain fatty acids (SCFAs) are linked with pathology of Alzheimer’s disease (AD)- a debilitating public health problem in older adults. However, strategies to beneficially modulate gut microbiota and its sensing signaling pathways remain largely unknown. Here, we screened, validated and established the agonists of free fatty acid receptor 2 (FFAR2) signaling, which senses beneficial signals from SCFAs produced by microbiota in the gut. We demonstrated that inhibition of FFAR2 signaling increases amyloid-beta (Aβ) stimulated neuronal toxicity. Thus, we screened FFAR2 agonists, using in-silico library of more than 144,000 natural compounds, and 15 compounds were selected based on binding with FFAR2 agonist sites. Further, cell culture toxicity and FFAR2 stimulatory experiments demonstrated that Fenchol (a natural compound commonly present in basil) was potent FFAR2 agonist in neuronal cells. Interestingly, we also demonstrated that Fenchol protects Aβ-stimulated neurodegeneration in FFAR2 dependent manner. In addition, Fenchol reduced AD like phenotypes such as Aβ-accumulation and, learning and memory behaviors in Caenorhabditis (C.) elegans. Fenchol increased Aβ-clearance by increasing proteasome/lysosome activity and reduced senescence in neuronal cells. These results demonstrated that the inhibition of FFAR2 signaling promotes Aβ-induced neurodegeneration, while activating it by Fenchol as a natural agonist reverse it by promoting Aβ-clearance and reducing cellular senescence; thus stimulation of FFAR2 signaling can be a therapeutic approach to prevent/ treat AD.

Abstract: Background: COVID-19 is a respiratory disease that eventually became pandemic with 300 million people infected around the world. Alongside the improvement in COVID-19 management and vaccine development, identifying biomarkers for COVID-19 has recently reported to help in early prediction and managing severe cases which might improve outcome. The Aim of our study was to find out if there is any correlation between clinical severity and elevated hematological and biochemical markers in Covid-19 patients and its effect on the outcome Methods: We have collected data retrospectively of socio-demographic, medical history, biomarkers, and diseases outcome from five hospitals and health institutions in the Kingdom of Saudi Arabia. Results: Pneumonia was the most common presentation of COVID 19 in our cohort. All biomarkers (D-Dimer, CRP, troponin, LDH and ferritin) except for the mean lowest white blood cells were found to have significant correlation (p<0.05) with worse COVID-19 disease outcomes. There was a sig-nificant association between the inflammatory biomarkers and the disease severity of COVID 19 patients (p<0.001). Patients with evidence of severe respiratory disease particularly who required mechanical ventilation (MV) had higher biomarkers, when compared to those with stable respiratory condition (p<0.001). Conclusion: Identifying biomarkers predicts outcome for COVID-19 patients and may significantly help in the management.

Phosphate (Pi) deficiency reduces nodule formation and development in different legume species including common bean. Despite the significant progress in the understanding of the genetic responses underlying the adaptation of nodules to Pi deficiency, it is still unclear whether this nutritional deficiency interferes with the molecular dialog between legumes and rhizobia, if so, what part of the molecular dialog is impaired? In this study, we provide evidence demonstrating that Pi deficiency negatively affects critical early molecular and physiological responses required for a successful symbiosis between common bean and rhizobia. We demonstrated that the infection thread formation and the expression of PvNSP2, PvNIN, and PvFLOT2, genes controlling the nodulation process, were significantly reduced in Pi-deficient common bean seedlings. Further transcriptional analysis revealed that the expression of hormones-related genes is compromised in Pi-deficient seedlings inoculated with rhizobia. Additionally, we showed that regardless of the presence or absence of rhizobia, the expression of PvRIC1 and PvRIC2, two genes participating in the autoregulation of nodule number, was higher in Pi-deficient seedlings than in control seedlings. The data presented in this study shed light on the understanding of how Pi deficiency impacts the early steps of the symbiosis between common bean and rhizobia.

This report is on magneto-electric (ME) interactions in bulk composites with coaxial nanofibers of nickel zinc ferrite and PZT. Core-shell fibers of PZT and Ni1-x Znx Fe2 O4 (NZFO) with x = 0-0.5 were made by electrospinning. Both kind of fibers, either with ferrite- or PZT-core and with diameters in the range 1-3 m were made. Electron- and scanning probe microscopy images indicted well-formed fibers with uniform core and shell structures and defect free interface. X-ray diffraction data for fibers annealed at 700-900 C did not show any impurity phases. Magnetization, magnetostriction, ferromagnetic resonance, and polarization P versus electric field E measurements confirmed the ferroic nature of the fibers. For ME measurements the fibers were pressed into disks and rectangular platelets and then annealed at 900-1000 C for densification. Strengths of strain mediated ME coupling were measured by H-induced changes in remnant polarization Pr and by low-frequency ME voltage coefficient (MEVC). The fractional change in Pr under H increased in magnitude, from +3% for disks of NFO– PZT to -82% for NZFO (x=0.3)-PZT, and further increase in x resulted in a decrease to a value of -3% for x=0.5. Low-frequency MEVC measured in disks of the core-shell fibers ranged from 6 mV/cm Oe to 37 mV/cm Oe. The fractional changes in Pr and the MEVC values were an order of magnitude higher than for bulk samples containing mixed fibers with random distribution of NZFO and PZT. The bulk composites with coaxial fibers have the potential for use as magnetic field sensors and in energy harvesting applications.

Cellular senescence accumulates with age and has been shown to impact numerous physiological and pathological processes, including immune function. The role of cellular senescence in cancer is multifaceted, but the impact on immune checkpoint inhibitor response and toxicity has not been fully evaluated. In this review, we evaluate the impact of cellular senescence in various biological compartments, including the tumor, the tumor microenvironment, and the immune system on immune checkpoint inhibitor efficacy and toxicity. We provide an overview of the impact of cellular senescence in normal and pathological contexts and examine recent studies that have connected aging and cellular senescence to immune checkpoint inhibitor treatment in both the pre-clinical and clinical contexts. Overall, senescence plays a multi-faceted, context-specific role, and has been shown to modulate immune-related adverse event incidence as well as immune checkpoint inhibitor response.