查看更多>>摘要：The human immunity has a pivotal role in nutrition acquisition from the pathogens and damaged body tissue during the SARS-CoV-2 virus infection， which may lead to transient overnutrition in the patients， lead to lipotoxicity and further damage in non-adipose tissues， and cause hyperinflammation and cytokine storm in severe cases of COVID-19。 In view of this， high-quality clinical trials on restrictive eating should be designed to investigate the possible benefits of food intake restriction on patients' recovery from COVID-19 disease。
查看更多>>摘要：Cancer cells survive and grow despite various advanced anti-cancer therapy。 To overcome this antineoplastic resistance， adjuvant therapy is often required to prevent cancer cells' immunoescape capacity。 Established tumors build a stressful and hostile microenvironment in order to escape protective innate and adaptive immune responses。 Specific conditions and factors within tumors， including hypoxia， nutrient starvation， acidic pH， and increased levels of free radicals， provoke a state of "endoplasmic reticulum stress" in both malignant cells and infiltrating myeloid cells。 The stimulated endoplasmic reticulum stress can affect cancer progression via crosstalks with the innate immune system。 Recently， the immunosuppressive activities of myeloid cells in the development of antineoplastic resistance are gaining more attention。 Based on all these available data， we hypothesize that interruption of innate-immune recognition-mediated emergency myelopoiesis may be beneficial in halting cancer progression。
查看更多>>摘要：Some organophosphorus compounds (OPs) can cause a type of delayed neurotoxicity in human being， which is known as organophosphorus-induced delayed neuropathy (OPIDN)。 Signs and symptoms of the patients include tingling and sensory loss of the hands and feet， followed by progressive muscle weakness in the lower and upper limbs， and ataxia。 Pathologically， OPIDN are characterized by distal sensorimotor axonopathy due to the distal axonal degeneration of nerve tracts located in central and peripheral nervous systems。 The morphological pattern of the distal axonopathy is similar to Wallerian degeneration that occurs after nerve injury in vitro。 It is generally acknowledged that inhibition and subsequent aging of neuropathy target esterase (NTE) is required for the occurrence of OPIDN。 However， the underlying mechanisms through which NTE triggers axonal degeneration in OPIDN is still largely unclear。 Recently， sterile alpha and toll/interleukin receptor motif-containing protein 1 (SARM1) has been identified as a key player in Wallerian degeneration。 In physical and chemical transection of axons， SARM1 was found to promotes axon degeneration by hydrolyzing NAD+。 By contrast， SARM1 deficiency could prevent neuron degeneration in response to a wide range of insults。 Furthermore， SARM1 can also translocate to mitochondria and cause mitochondrial damage， thus triggering axon degeneration and neuron death。 These findings suggested the existence of a pathway in axonal degeneration that might be targeted therapeutically。 Here， we hypothesize that SARM1 activation after NTE inhibition and aging might be an etiological factor in OPIDN that regulates Wallerian-like degeneration。 Analysing SARM1 mediated NAD degeneration pathway and its upstream activators in OPIDN could contribute to the development of novel therapies to treat OPIDN。
查看更多>>摘要：Alterations within consciousness in schizophrenia can be evidenced by impediments in self-awareness and loss of agency。 Ned Block's definition of access consciousness is applied in order to further delineate cognitive deficits involving reflective thought and autonoetic thinking in persons with schizophrenia。 Current theories on the nature and functioning of consciousness are discussed， which include Global Workspace Theory and metarepresentational characterizations。 These describe a recursive， integrative quality to consciousness， contributed to by the functions of access consciousness， that is relevant in examining cognitive deficits in schizophrenia。 The integrative deficit that is described as operating in conscious process involves a failure to incorporate prior outputs from a separate cognitive task and integrate these into a novel working schema。 The alterations in access consciousness in persons with schizophrenia appear to be a consequence of disrupted integrative cognitive functions。 An anteceding problem with cortical circuits involving integrative functions related to access consciousness is therefore hypothesized to manifest as subsequent cognitive dysfunction that leads to symptoms of schizophrenia。 Constitutive failures to integrate information in schizophrenia could lead to an inability to create experiential unity and manage content in autonoetic consciousness。 Some of the aberrant reasoning manifested by persons with schizophrenia， including problems with hierarchical relational reasoning， model-based-learning， J-con， ipseity， and source monitoring， could also reflect alterations in access consciousness， and their investigation offers additional approaches for scientific inquiry。
查看更多>>摘要：Currently， a plethora of information has been accumulated concerning COVID-19， including the transmission pathway of SARs-CoV-2。 Thus， we retrieved targets associated with the development of COVID-19 via PubChem。 A total of 517 targets were identified， and signaling pathways responded after infection of SARs-CoV-2 in humans constructed a bubble chart using RPackage。 The bubble chart result suggested that the key signaling pathway against COVID-19 was the estrogen signaling pathway associated with AKT1， HSP90AB1， BCL2 targets。 The three targets have the strongest affinity with three ligands-Akti-1/2， HSP990， S55746， respectively。 In conclusion， this work provides three key elements to alleviate COVID-19 symptoms might be anti-inflammatory effects on SARsCoV-2-infected lung cells。
查看更多>>摘要：Blood pathogenic trypanosomatids as Trypanosoma cruzi， the causative agent of Chagas Disease， have specialized systems to export virulence factors into host cells。 Extracellular vesicles shed by T。 cruzi promote infection susceptibility of host cells。 Sterile inflammation is part of the innate immune response to molecules released upon tissue injury and is collectively indicated as damage-associated molecular patterns。 The complex regulatory pathways that modulate the generation and trafficking of damage-associated molecular patterns are being actively investigated， given their potential to provide a relevant understanding of the physiological and pathological conditions of various diseases that affect humans。 However， the common biochemical pathway in the generation of damage-associated molecular patterns and extracellular vesicles shed by T。 cruzi is unclear。 I propose the following hypothesis: some contents of extracellular vesicles from T。 cruzi-infected cells can act as damage-associated molecular patterns during T。 cruzi infection。 This hypothesis is based on two elements to support it: first， damage-associated molecular patterns can be secreted or exposed by living cells undergoing a life-threatening stress。 The second is the composition of extracellular vesicles shed by T。 cruzi and released by the host cells during T。 cruzi infection。 Additionally， we discuss the implications of extracellular vesicles shed by T。 cruzi and damage-associated molecular patterns in Chagas disease。
查看更多>>摘要：Two tiny muscles are attached to the ossicles of the middle ear: the stapedius， whose role as a protector of the inner ear against loud noise has been widely accepted， and the tensor tympani， which remains a mystery since no valid method of detecting its contraction has yet been developed。 However， tonic contraction of the tensor tympani has been associated with a number of otological conditions including fullness， tinnitus， slight hearing loss， and Menie`re-like findings。 Our hypothesis is that an easily recognizable sign in the acoustic immittance testing that is part of almost every basic audiological evaluation indicates the contraction of the tensor tympani。 During acoustic reflex assessment， a loud stimulus causes a bilateral contraction of the stapedial muscles and an increase in impedance which appears as a deflection in the tracing of the immittance test results。 In the case of a contracted tensor tympani， when an intense sound is sent to provoke the acoustic reflex， the stapedius must overcome its resistance which would otherwise have the opposite effect on the footplate。 This effort can be seen as a small peak or "preshoot" preceding the greater negative deflection of the impedance。 We report the cases of ten patients with unilateral aural symptoms such as tinnitus， impaired noise tolerance， fullness， ear pressure and/ or ear discomfort during chewing; the preshoot was present only in the symptomatic ear。 If further studies confirm our hypothesis， this could give rise to new therapeutical strategies aimed at reducing contraction of the tensor tympani and balancing its function。
查看更多>>摘要：Alpha-casozepine (alpha CZP)， a tryptic hydrolysate of milk casein is a decapeptide shown to promote sleep and produce anxiolytic or anticonvulsant activity。 Intriguingly， studies indicate structural similarities to benzodiazepine (BZD)-like molecules (e。g。， diazepam)， resulting in positive modulation of gamma-aminobutyric acid A type (GABA(A)) receptors。 However， some unexplained anomalous behaviour of alpha-CZP includes 1) 1000 times less affinity for BZD site on GABA(A) receptor in vitro conditions， whereas in vivo it showed 10-fold increased affinity when compared to diazepam; 2) anxiolytic effects were observed only in stressed conditions and 3) unlike diazepam， it failed to exhibit dependence or habituation。 Interestingly， neurosteroids like allopregnanolone or its analogues that are synthesized de novo have both genomic and non-genomic actions。 The rapid nongenomic neuronal inhibition of these compounds is mediated by GABA(A) receptors through autocrine and paracrine actions。 Studies have shown that changes in the levels of neurosteroids during acute (rise) and chronic stress (decreased)， consequently， altering the senetivity of GABA(A) receptor subunits。 Neurosteroids even at low concentration (nanomolar range) potentiate the response of GABA indirectly， while at higher concentrations they directly activate the receptor-channel complex。 Interestingly， coadministration of neurosteroids and BZPs has shown not only to prevent the development of tolerance of BZP and augmented recovery from BZP withdrawal anxiety and hyperactivity in mice。 The combination also produced synergetic anxiolytic effects。 Taken together， the evidence suggests possible implications of neurosteroids in the actions of CZP via BZD receptors。 The present hypothesis brings out the possible role of neurosteroids and the various factors that might participate in CZPinduce anxiolytic effects。
NSTL
Elsevier