Maresin 1 alleviates neuroinflammation and cognitive decline in a mouse model of cecal ligation and puncture

Objective:Inflammation in the central nervous system plays a crucial role in the occurrence and development of sepsis-associated encephalopathy.This study aims to explore the effects of maresin 1(MaR1),an anti-inflammatory and pro-resolving lipid mediator,on sepsis-induced neuroinflammation and cognitive impairment.Methods:Mice were randomly assigned to 4 groups:A sham group(sham operation+vehicle),a cecal ligation and puncture(CLP)group(CLP operation+vehicle),a MaR1-LD group(CLP operation+1 ng MaR1),and a MaR1-HD group(CLP operation+10 ng MaR1).MaR1 or vehicle was intraperitoneally administered starting 1 h before CLP operation,then every other day for 7 days.Survival rates were monitored,and serum inflammatory cytokines[tumor necrosis factor alpha(TNF-α),interleukin(IL)-1β,and IL-6]were measured 24 h after operation using enzyme-linked immunosorbent assay(ELISA).Cognitive function was assessed 7 days after operation using the Morris water maze(MWM)test and novel object recognition(NOR)task.The mRNA expression of TNF-α,IL-1β,IL-6,inducible nitric oxide synthase(iNOS),IL-4,IL-10,and arginase 1(Arg1)in cortical and hippocampal tissues was determined by real-time reverse transcription PCR(RT-PCR).Western blotting was used to determine the protein expression of iNOS,Arg1,signal transducer and activator of transcription 6(STAT6),peroxisome proliferator-activated receptor gamma(PPARγ),and phosphorylated STAT6(p-STAT6)in hippocampal tissue.Microglia activation was visualized via immunofluorescence.Mice were also treated with the PPARγantagonist GW9662 to confirm the involvement of this pathway in MaR1’s effects.Results:CLP increased serum levels of TNF-α,IL-1β,and IL-6,and reduced body weight and survival rates(all P<0.05).Both 1 ng and 10 ng doses of MaR1 significantly reduced serum TNF-α,IL-1β,and IL-6 levels,improved body weight,and increased survival rates(all P<0.05).No significant difference in efficacy was observed between the 2 doses(all P>0.05).MWM test and NOR task indicated that CLP impaired spatial learning,which MaR1 mitigated.However,GW9662 partially reversed MaR1’s protective effects.Real-time RTPCR results demonstrated that,compared to the sham group,mRNA expression of TNF-α,IL-1β,and iNOS significantly increased in hippocampal tissues following CLP(all P<0.05),while IL-4,IL-10,and Arg1 showed a slight decrease,though the differences were not statistically significant(all P>0.05).Compared to the CLP group,both 1 ng and 10 ng MaR1 decreased TNF-α,IL-1β,and iNOS mRNA expression in hippocampal tissues and increased IL-4,IL-10,and Arg1 mRNA expression(all P<0.05).Immunofluorescence results indicated a significant increase in Iba1-positive microglia in the hippocampus after CLP compared to the sham group(P<0.05).Administration of 1 ng and 10 ng MaR1 reduced the percentage area of Iba1-positive cells in the hippocampus compared to the CLP group(both P<0.05).Western blotting results showed that,compared to the CLP group,both 1 ng and 10 ng MaR1 down-regulated the iNOS expression,while up-regulated the expression of Arg1,PPARγ,and p-STAT6(all P<0.05).However,the inclusion of GW9662 counteracted the MaR1-induced upregulation of Arg1 and PPARγcompared to the MaR1-LD group(all P<0.05).Conclusion:MaR1 inhibits the classical activation of hippocampal microglia,promotes alternative activation,reduces sepsis-induced neuroinflammation,and improves cognitive decline.

The rate of deadwood decomposition processes in tree stand gaps resulting from bark beetle infestation spots in mountain forests

Decaying wood is an essential element of forest ecosystems and it affects its other components.The aim of our research was to determine the decomposition rate of deadwood in various humidity and thermal conditions in the gaps formed in the montane forest stands.The research was carried out in the Babiog orski National Park.The research plots were marked out in the gaps of the stands,which were formed as a result of bark beetle gradation.Control plots were located in undisturbed stands.The research covered wood of two species–spruce and beech in the form of cubes with dimensions of 50 mm×50 mm×22 mm.Wood samples were placed directly on the soil surface and subjected to laboratory analysis after 36 months.A significant influence of the wood species and the study plot type on the physicochemical properties of the tested wood samples was found.Wood characteristics strongly correlated with soil moisture.A significantly higher mass decline of wood samples was recorded on the reference study plots,which were characterized by more stable moisture conditions.Poorer decomposition of wood in the gaps regardless of the species is related to lower moisture.The wood species covered by the study differed in the decomposition rate.Spruce wood samples were characterized by a significantly higher decomposition rate compared to beech wood samples.Our research has confirmed that disturbances that lead to the formation of gaps have a direct impact on the decomposition process of deadwood.

Neuroprotective effects of G9a inhibition through modulation of peroxisome-proliferator activator receptor gamma-dependent pathways by miR-128

Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative stress.Likewise,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s disease.Therefore,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and neuroinflammation.To better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor UNC0642.We found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)mRNA.Accordingly,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control group.We also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a inhibitor.To confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative insult.In this setting,treatment with G9a inhibitor increases both cell survival and antioxidant enzymes.Moreover,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and apoptosis.In addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers expression.Finally,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a inhibition.Altogether,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.

Gut microbiota-astrocyte axis: new insights into age-related cognitive decline

With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.

Glymphatic system function in diverse glucose metabolism states

The rising prevalence of diabetes and prediabetes globally necessitates a deeper understanding of associated complications,including glymphatic system dysfunction.The glymphatic system,crucial for brain waste clearance,is implicated in cognitive decline and neurodegenerative diseases like Alzheimer’s disease.This letter explores recent research on glymphatic function across different glucose metabolism states.Tian et al’s study reveals significant glymphatic dysfunction in type 2 diabetes mellitus patients,evidenced by lower diffusion tensor imaging analysis along perivascular space indices compared to those with normal glucose metabolism and prediabetes.The research also reveals a link between glymphatic dysfunction and cognitive impairment.Additional research underscores the role of glymphatic impairment in neurodegenerative diseases.These findings highlight the importance of integrating glymphatic health into diabetes management and suggest potential biomarkers for early diagnosis and targeted therapeutic interventions.

Brain Functional Network Changes in Patients with Poststroke Cognitive Impairment Following Acupuncture Therapy

Background: The mechanisms by which acupuncture affects poststroke cognitive impairment (PSCI) remain unclear. Objective: To investigate brain functional network (BFN) changes in patients with PSCI after acupuncture therapy. Methods: Twenty-two PSCI patients who underwent acupuncture therapy in our hospital were enrolled as research subjects. Another 14 people matched for age, sex, and education level were included in the normal control (HC) group. All the subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans;the PSCI patients underwent one scan before acupuncture therapy and another after. The network metric difference between PSCI patients and HCs was analyzed via the independent-sample t test, whereas the paired-sample t test was employed to analyze the network metric changes in PSCI patients before vs. after treatment. Results: Small-world network attributes were observed in both groups for sparsities between 0.1 and 0.28. Compared with the HC group, the PSCI group presented significantly lower values for the global topological properties (γ, Cp, and Eloc) of the brain;significantly greater values for the nodal attributes of betweenness centrality in the CUN. L and the HES. R, degree centrality in the SFGdor. L, PCG. L, IPL. L, and HES. R, and nodal local efficiency in the ORBsup. R, ORBsupmed. R, DCG. L, SMG. R, and TPOsup. L;and decreased degree centrality in the MFG. R, IFGoperc. R, and SOG. R. After treatment, PSCI patients presented increased degree centrality in the LING.L, LING.R, and IOG. L and nodal local efficiency in PHG. L, IOG. R, FFG. L, and the HES. L, and decreased betweenness centrality in the PCG. L and CUN. L, degree centrality in the ORBsupmed. R, and nodal local efficiency in ANG. R. Conclusion: Cognitive decline in PSCI patients may be related to BFN disorders;acupuncture therapy may modulate the topological properties of the BFNs of PSCI patients.

Importance of Stewards and Other Protection Efforts for Conservation of Red Knots (Calidris canutus rufa) and Other Shorebirds on Delaware Bay, New Jersey

Understanding the factors that contribute to population stability in long-distance migrant birds is increasingly important, particularly given global climate change, sea level rise, and loss or disturbance at essential habitats. While the populations of most shorebirds are declining worldwide, those that migrate through Delaware Bay, New Jersey and Delaware, are declining at the most rapid rate despite conservation efforts. In this paper, we 1) provide background information on population declines of red knots (Calidris canutus rufa) using Delaware Bay, threats to their foraging, and efforts to reduce threats, 2) summarize briefly our studies of the effects of human activities on knots and other shorebirds, 3) present data on management efforts to protect knots and other shorebirds from the activities of people, and 4) discuss the efficacy of such efforts (usually referred to as “decreasing the effect of human disturbances”). The Shorebird Project on Delaware Bay is over 25 years old and provides long-term data to help assess the status of shorebird numbers, particularly for red knot, as well as the density of horseshoe crabs (Limulus polyphemus) and their eggs. Red knots have continued to decline even more precipitously in the last few years, presenting cause for concern. Protective efforts have been successful in reducing human disruption on the N.J. Delaware Bay beaches, but the lack of uniformity in implementation across the New Jersey side, and across the whole Bay have hampered further improvements. Implementation of signs, fencing, and stewards on some beaches significantly enhanced the use of these beaches by red knots, determined by examining the use of beaches pre- and post-implementation. Implementation of fencing and stewards had the greatest effect. From 1986 to 2018, there was a significant shift in the percent of Delaware Bay red knots using the NJ side, where protection efforts had been implemented on many of the beaches. Merely restricting access (without fencing or other efforts) did not result in more knots using the beaches post-restriction. This is the first paper that clearly shows the protective effects of having beach stewards. We discuss the long-term needs for continued management of Delaware Bay beaches, and other beaches coastwide, and of determining the causes of population declines of red knots.

China's Electrolytic Aluminum Output Declined By 3% On Y-OY Basis In Q1

In the first quarter China’s electrolytic aluminum output dropped by 3%on Y-o-Y basis to about 7.45 million tonnes.In March2016 China’s electrolytic aluminum output was about 2.48 million tonnes,basically on par with that of February.In 2015 due to sluggish market condition,China’s electrolytic aluminum factories reduced output by about3.97 million tonnes.Furthermore,new

Shanghai apparel sales value and sales volume both declined in June (Ⅱ)

Men’s suit:Top3 are in stable pattern The accumulated sales volume of Men’s suit was 249,000 pieces by the end of June 2011,11,000 pieces more than a

Shanghai apparel sales value and sales volume both declined in June (Ⅰ)

According to the online periodic statistics statement of Shanghai Apparel Association,Shanghai apparel sales volume in 10 major department stores in June was 849,000 pieces,reduced 116,000 pieces from the previous

The export of textile and apparel declined by small margin in January-July

According to customs statistics, on August 10th, in January-July 2012 ,China’s foreign trade imports and exports valued at USD 2,168.37 billion. Compared with the same period in 2011 increased 7.1%. Among them, exports worth USD 1,131.24 billion,

Does pollinator dependence decrease along elevational gradients?

Plants have long been thought to be less dependent on pollinators for seed production at higher elevations due to adverse pollination environments.However,recent research has yet to consistently support the generality of this expectation.In this study,we asked whether pollinator dependence decreases along an elevational gradient and how it varies with various reproductive traits.To answer these questions,we quantified pollinator-plant associations and various reproductive traits for 112 flowering plants spanning a large elevational gradient(990-4260 m a.s.l.)in the Qinghai-Tibet Plateau.We found that flowering plants in the Qinghai-Tibet Plateau region are highly dependent on pollinators for seed production(76.2%of seed production was contributed by animal pollinators and 44.6%of plants would produce no seed without pollinator visitation).Contrary to our expectation,there was no significant elevational gradient in pollinator dependence index.Although the pollinator dependence index was not significantly correlated with pollen limitation,flower size,floral longevity,or reward type,it was correlated with compatibility status and flowering time.These findings indicate that pollinator dependence does not decrease along an elevational gradient in the Qinghai-Tibet Plateau.Our study also highlights the severe vulnerability of flowering plant seed production to pollinator declines under global change in the Qinghai-Tibet Plateau region,particularly for early-flowering or self-incompatible plants growing at higher elevations(e.g.,subnival belt).

Efficacy of prednisone combined with mycophenolate mofetil for immunoglobulin A nephropathy with moderate-to-severe renal dysfunction

BACKGROUND Immunoglobulin A nephropathy(IgAN)is a common form of chronic glomer-ulonephritis.Currently,IgAN is one of the main causes of chronic renal failure in China;its prognosis varies greatly between patients,with renal function at the time of diagnosis and prognosis being strongly correlated.Mycophenolate mofetil(MMF)is a drug with a good immunomodulatory effect and is commonly used clinically.However,its effects in IgAN have not yet been clearly demonstrated.Therefore,herein,we retrospectively compared the effectiveness and safety of prednisone alone or combined with MMF for the treatment of primary IgAN with moderate-to-severe renal impairment.METHODS Between January 2011 and December 2020,200 patients with moderate-to-severe IgAN were included in this study,all of whom were admitted to Wuxi People's Hospital affiliated with Nanjing Medical University.All patients underwent a renal puncture biopsy,which revealed primary IgAN with a glomerular filtration rate(GFR)of 30–60 mL/min.The patients were divided into a glucocorticoid therapy group(GTG)and an immunosuppressive therapy group(ITG)according to the different treatment regimens,with 100 patients in each group.Based on general treatments,such as angiotensin-converting enzyme inhibitors/angiotensin receptor blockers,patients in the GTG were administered prednisone 0.5–0.8 mg/(kg·d^(-1))for 4–8 wk,which was reduced by 5 mg every two weeks until the maintenance(30 mg/d)dose was reached and maintained for 12 mo.In the ITG,MMF was administered at 1.0 g/d for 6–12 mo,followed by a maintenance dosage of 0.5 g/d for 12 mo.Age,sex,blood pressure,24-h urinary egg white measurement,serum creatinine(Scr),blood uric acid,blood albumin,blood potassium(K),hemoglobin,GFR,alanine aminotransferase,total cholesterol(T-CHO),fasting blood glucose,and body mass index were recorded.The 24-h urinary protein,Scr,and GFR levels were recorded 3,6,9,and 12 mo after treatment.Follow-up data were also collected.RESULTS No discernible differences existed between the two groups in terms of age,sex,blood pressure,creatinine,24-h urinary protein level,GFR,or other biochemical indicators at the time of enrollment.Both regimens significantly reduced the 24-h urinary protein quantitation and stabilized renal function.Nine months after treatment,the 24-h urinary protein and Scr of the ITG decreased more significantly than those of the GTG.By the 12th month of treatment,the 24-h urinary protein and Scr in both groups continued to decrease compared to those by the 9th month.In addition,the overall response rate in the ITG was significantly higher than that in the GTG.The occurrence of side effects did not vary significantly between the two regimens;however,endpoint events were significantly more common in the GTG than in the ITG.The follow-up time for the GTG was noticeably lower than that for the ITG.CONCLUSION Prednisone combined with MMF was effective for the treatment of IgAN with moderate-to-severe renal dysfunction.

Coupling between the Cenozoic west Pacific subduction initiation and decreases of atmospheric carbon dioxides

At the beginning of the Cenozoic,the atmospheric CO_(2)concentration increased rapidly from~2000 ppmv at 60 Ma to~4600 ppmv at 51 Ma,which is 5–10 times higher than the present value,and then continuous declined from~51 to 34 Ma.The cause of this phenomenon is still not well understood.In this study,we demonstrate that the initiation of Cenozoic west Pacific plate subduction,triggered by the hard collision in the Tibetan Plateau,occurred at approximately 51 Ma,coinciding with the tipping point.The water depths of the Pacific subduction zones are mostly below the carbonate compensation depths,while those of the Neo-Tethys were much shallower before the collision and caused far more carbonate subducting.Additionally,more volcanic ashes erupted from the west Pacific subduction zones,which consume CO_(2).The average annual west Pacific volvano eruption is 1.11 km~3,which is higher than previous estimations.The amount of annual CO_(2)absorbed by chemical weathering of additional west Pacific volcanic ashes could be comparable to the silicate weathering by the global river.We propose that the initiation of the western Pacific subduction controlled the long-term reduction of atmospheric CO_(2)concentration.

Nutrient retranslocation strategies associated with dieback of Pinus species in a semiarid sandy region of Northeast China

In the semiarid sandy region of Northeast China,Mongolian pine(Pinus sylvestris var.mongolica)suffers dieback after the age of 35,while Japanese red pine(Pinus densiflora)and Chinese pine(Pinus tabuliformis)stay healthy.Foliar nutrient retranslocation reflects the nutrient conservation and utilization mechanism of plants in response to their habitats.However,the nutrient retranslocation strategies employed by three Pinus tree species to cope with nutrient limitations remain largely unknown.For this study,we investigated the seasonal variations in nitrogen(N)and phosphorus(P)concentrations of Mongolian pine,Japanese red pine,and Chinese pine plantations in terms of the green needles of all ages,senesced needles,and soil.Further,the N retranslocation efficiency(NRE),and P retranslocation efficiency(PRE),and correlations between the N:P ratios of needles and soil were analyzed.The results showed that,except for the spring NRE in 1-year-old needles of Mongolian pine,the spring NRE and PRE in 1-and 2-year-old needles of the three tree species were greater than zero.The autumn PRE was higher than zero for Mongolian pine,but lower than zero for Japanese red pine and Chinese pine.Among the three Pinus species,Mongolian pine showed greater spring PRE in 2-year-old needles,and PRE from 1-to 2-yearold needles,and from 2-year-old needles to litter.However,Japanese red pine had higher P concentrations and lower N:P ratios in senesced needles,while greater PRE was found in Chinese pine litter.Significant relationships between the N:P ratios were found in the current year and 1-year-old needles and soil in the Mongolian pine plantation,while there was an insignificant relationship between the N:P ratios of the needles and soil in the Chinese pine plantation.Thus,for Mongolian pine,the removal of P from needles in autumn,and higher P translocation from older needles under P-deficient soil may have contributed to the tree dieback.In contrast,Japanese red pine and Chinese pine stored P in their needles during autumn.Japanese red pine returned more P to the soil via litter,while Chinese pine maintained N:P homeostasis and increased P withdrawal prior to needle abscission.

Shale oil enrichment evaluation and production law in Gulong Sag,Songliao Basin,NE China

Based on the results of drilling,tests and simulation experiments,the shales of the Cretaceous Qingshankou Formation in the Gulong Sag of the Songliao Basin are discussed with respect to hydrocarbon generation evolution,shale oil occurrence,and pore/fracture evolution mechanism.In conjunction with a substantial amount of oil testing and production data,the Gulong shale oil enrichment layers are evaluated and the production behaviors and decline law are analyzed.The results are drawn in four aspects.First,the Gulong shales are in the stage of extensive hydrocarbon expulsion when R_(0) is 1.0%-1.2%,with the peak hydrocarbon expulsion efficiency of 49.5%approximately.In the low-medium maturity stage,shale oil migrates from kerogen to rocks and organic pores/fractures.In the medium-high maturity stage,shale oil transforms from adsorbed state to free state.Second,the clay mineral intergranular pores/fractures,dissolution pores,and organic pores make up the majority of the pore structure.During the transformation,clay minerals undergo significant intergranular pore/fracture development between the minerals such as illite and illite/smectite mixed layer.A network of pores/fractures is formed by organic matter cracking.Third,free hydrocarbon content,effective porosity,total porosity,and brittle mineral content are the core indicators for the evaluation of shale oil enrichment layers.Class-I layers are defined as free hydrocarbon content equal or greater than 6.0 mg/g,effective porosity equal or greater than 3.5%,total porosity equal or greater than 8.0%,and brittle mineral content equal or greater than 50%.It is believed that the favourable oil layers are Q2-Q3 and Q8-Q9.Fourth,the horizontal wells in the core area of the light oil zone exhibit a high cumulative production in the first year,and present a hyperbolic production decline pattern,with the decline index of 0.85-0.95,the first-year decline rate of 14.5%-26.5%,and the single-well estimated ultimate recovery(EUR)greater than 2.0×10^(4)t.In practical exploration and production,more efforts will be devoted to the clarification of hydrocarbon generation and expulsion mechanisms,accurate testing of porosity and hydrocarbon content/phase of shale under formation conditions,precise delineation of the boundary of enrichment area,relationship between mechanical properties and stimulated reservoir volume,and enhanced oil recovery,in order to improve the EUR and achieve a large-scale,efficient development of shale oil.

Reasons and effects of the decline of willing related potential living kidney donors

BACKGROUND Although the availability of related living donors(LDs)provides a better chance for receiving kidney transplantation(KT),the evaluation protocols for LD selection remain a safeguard for the LD’s safety.These protocols are variable from one center to another,resulting in variable rates of decline of the potential LDs(PLDs).The decline of willing PLDs may occur at any stage of evaluation,starting from the initial contact and counseling to the day of operation.AIM To identify the causes of the decline of PLDs,the predictors of PLD candidacy,and the effect on achieving LDKT.METHODS A retrospective study was performed on the willing PLDs who attended our outpatient clinic for kidney donation to their related potential recipients between October 2015 and December 2022.The variables influencing their candidacy rate and the fate of their potential recipients were studied.Two groups of PLDs were compared:Candidate PLDs after a completed evaluation vs non-candidate PLDs with a complete or incomplete evaluation.A multivariate logistic regression was performed to assess the factors contributing to the achievement of PLD candidacy.RESULTS Of 321 willing PLDs,257 PLDs(80.1%)accessed the evaluation to variable extents for 212 potential recipients,with a mean age(range)of 40.5±10.4(18-65)years,including 169 females(65.8%).The remaining 64 PLDs(19.9%)did not access the evaluation.Only 58 PLDs(18.1%)succeeded in donating,but 199 PDLs(62.0%)were declined;exclusion occurred in 144 PLDs(56.0%)for immunological causes(37.5%),medical causes(54.9%),combined causes(9.7%),and financial causes(2.1%).Regression and release occurred in 55 PLDs(17.1%).The potential recipients with candidate PLDs were not significantly different from those with non-candidate PLDs,except in age(P=0.041),rates of completed evaluation,and exclusion of PLDs(P<0.001).There were no factors that independently influenced the rate of PLD candidacy.Most patients who failed to have KT after the decline of their PLDs remained on hemodialysis for 6 mo to 6 years.CONCLUSION The rate of decline of willing related PLDs was high due to medical or immunological contraindications,release,or regression of PLDs.It reduced the chances of high percentages of potential recipients in LDKT.

Alzheimer’s disease risk after COVID-19:a view from the perspective of the infectious hypothesis of neurodegeneration

In light of the rising evidence of the association between viral and bacterial infections and neurodegeneration,we aimed at revisiting the infectious hypothesis of Alzheimer’s disease and analyzing the possible implications of COVID-19 neurological sequelae in long-term neurodegeneration.We wondered how SARS-CoV-2 could be related to the amyloid-βcascade and how it could lead to the pathological hallmarks of the disease.We also predict a paradigm change in clinical medicine,which now has a great opportunity to conduct prospective surveillance of cognitive sequelae and progression to dementia in people who suffered severe infections together with other risk factors for Alzheimer’s disease.

Association Between Constipation and a Reduction in Lower Limb Muscle Strength in Preoperative Patients with Thoracic Spinal Tumors

Objective To investigate the clinical symptoms experienced by patients with thoracic spinal tumors and verify the associated symptoms that are predictive of a decline in muscle strength in the lower limbs.Methods A single-center,retrospective cross-sectional study was conducted on in-patients diagnosed with epidural thoracic spinal tumors between January 2011 and May 2021.The study involved a review of electronic medical records and radiographs and the collection of clinical data.The differences in clinical manifestations between patients with constipation and those without constipation were analyzed.Binary logistic regression analyses were performed to identify risk factors associated with a decline in muscle strength in the lower limbs.Results A total of 227 patients were enrolled,including 131 patients with constipation and 96 without constipation.The constipation group had a significantly higher proportion of patients who experienced difficulty walking or paralysis compared to those without constipation prior to surgery(83.2%vs.17.7%,χ~2=99.035,P 0.001).Constipation(OR=9.522,95%CI:4.150±21.849,P 0.001)and urinary retention(OR=14.490,95%CI:4.543±46.213,P 0.001)were independent risk factors for muscle strength decline in the lower limbs.Conclusions The study observed that patients with thoracic spinal tumors who experienced constipation symptoms had a higher incidence of lower limb weakness.Moreover,the analysis revealed that constipation and urinary retention were independent risk factors associated with a preoperative decline in muscle strength of lower limbs.

Gut microbiota links with cognitive impairment in amyotrophic lateral sclerosis: A multi-omics study

Recently, cognitive impairments(CI) and behavioral abnormalities in patients with amyotrophic lateral sclerosis(ALS) have been reported. However, the underlying mechanisms have been poorly understood. In the current study, we explored the role of gut microbiota in CI of ALS patients. We collected fecal samples from 35ALS patients and 35 healthy controls. The cognitive function of the ALS patients was evaluated using the Edinburgh Cognitive and Behavioral ALS Screen. We analyzed these samples by using 16S rRNA gene sequencing as well as both untargeted and targeted(bile acids) metabolite mapping between patients with CI and patients with normal cognition(CN). We found altered gut microbial communities and a lower ratio of Firmicutes/Bacteroidetes in the CI group, compared with the CN group. In addition, the untargeted metabolite mapping revealed that 26 and 17 metabolites significantly increased and decreased, respectively, in the CI group, compared with the CN group. These metabolites were mapped to the metabolic pathways associated with bile acids. We further found that cholic acid and chenodeoxycholic acid were significantly lower in the CI group than in the CN group. In conclusion, we found that the gut microbiota and its metabolome profile differed between ALS patients with and without CI and that the altered bile acid profile in fecal samples was significantly associated with CI in ALS patients. These results need to be replicated in larger studies in the future.