Chiral Assembly of Perovskite Nanocrystals: Sensitive Discrimination of Amino Acid Enantiomers.

Chirality is a widespread phenomenon in nature and in living organisms and plays an important role in living systems. The sensitive discrimination of chiral molecular enantiomers remains a challenge in the fields of chemistry and biology. Establishing a simple, fast, and efficient strategy to discriminate the spatial configuration of chiral molecular enantiomers is of great significance. Chiral perovskite nanocrystals (PNCs) have attracted much attention because of their excellent optical activity. However, it is a challenge to prepare perovskites with both chiral and fluorescence properties for chiral sensing. In this work, we synthesized two chiral fluorescent perovskite nanocrystal assembly (PNA) enantiomers by using l- or d-phenylalanine (Phe) as chiral ligands. PNA exhibited good fluorescence recognition for l- and d-proline (Pro). Homochiral interaction led to fluorescence enhancement, while heterochiral interaction led to fluorescence quenching, and there is a good linear relationship between the fluorescence changing rate and l- or d-Pro concentration. Mechanism studies show that homochiral interaction-induced fluorescence enhancement is attributed to the disassembly of chiral PNA, while no disassembly of chiral PNA was found in heterochiral interaction-induced fluorescence quenching, which is attributed to the substitution of Phe on the surface of chiral PNA by heterochiral Pro. This work suggests that chiral perovskite can be used for chiral fluorescence sensing; it will inspire the development of chiral nanomaterials and chiral optical sensors.

Association between delayed ambulation and increased risk of adverse events after lumbar fusion surgery in elderly patients.

PURPOSE: The relationship between delayed ambulation (DA) and postoperative adverse events (AEs) following transforaminal lumbar interbody fusion (TLIF) in elderly patients remains elusive. The aim of our study was to evaluate the effects of DA on the postoperative AEs including complications, readmission and prolonged length of hospital stay (LOS). METHODS: This was a retrospective analysis of a prospectively established database of elderly patients (aged 65 years and older) who underwent TLIF surgery. The early ambulation (EA) group was defined as patients ambulated within 48 h after surgery, whereas the delayed ambulation (DA) group was patients ambulated at a minimum of 48 h postoperatively. The DA patients were 1:1 propensity-score matched to the EA patients based on age, gender and the number of fused segments. Univariate analysis was used to compare postoperative outcomes between the two groups, and multivariate logistic regression analysis was used to identify risk factors for adverse events and DA. RESULTS: After excluding 125 patients for various reasons, 1025 patients (≤ 48 h: N = 659 and > 48 h: N = 366) were included in the final analysis. After propensity score matching, there were 326 matched patients in each group. There were no significant differences in the baseline data and the surgery-related variables between the two groups (p > 0.05). The patients in the DA group had a significant higher incidence of postoperative AEs (46.0% vs. 34.0%, p = 0.002) and longer LOS (p = 0.001). Multivariate logistic regression identified that age, operative time, diabetes, and DA were independently associated with postoperative AEs, whereas greater age, higher international normalized ratio, and intraoperative estimated blood loss were identified as independent risk factors for DA. CONCLUSIONS: Delayed ambulation was an independent risk factor for postoperative AEs after TLIF in elderly patients. Older age, increased intraoperative blood loss and worse coagulation function were associated with delayed ambulation.

The implementation of enhanced recovery after surgery pathway in patients undergoing posterior thoracolumbar fusion for degenerative spinal deformity.

PURPOSE: The prevalence of degenerative spinal deformity (DSD) and the increased cost of correction surgery impose substantial burdens on the health care and insurance system. The aim of our study was to investigate the effects of the implementation of Enhanced Recovery After Surgery (ERAS) protocol on postoperative outcomes after complex spinal surgery. METHODS: A retrospective analysis of prospectively established database of DSD was performed. The consecutive patients who underwent open correction surgery for degenerative spinal deformity between August 2016 and February 2022 were reviewed. We extracted demographic data, preoperative radiographic parameters, and surgery-related variables. The ERAS patients were 1:1 propensity-score matched to a historical cohort by the same surgical team based on age, gender, BMI, and number of levels fused. We then compared the length of hospital stay (LOS), physiological functional recovery, and the rates of complications and readmissions within 90 days after surgery between the groups. RESULTS: There were 108 patients included, 54 patients in the ERAS cohort, and 54 patients matched control patients in the historical cohort. The historical and ERAS cohorts were not significantly different regarding demographic characteristics, comorbidities, preoperative parameters, operative time, and reoperation rate (P > 0.05). Patients in the ERAS group had significantly shorter postoperative LOS (12.0 days vs. 15.1 days, P = 0.001), average days of drain and urinary catheters placement (3.5 days vs. 4.4 days and 1.9 days vs 4.8 days, respectively), and lower 90-day readmission rate (1.8% vs. 12.9%, P = 0.027). The first day of assisted-walking and bowel movement occurred on average 1.9 days (2.5 days vs. 4.4 days, P = 0.001) and 1.7 days (1.9 days vs. 3.6 days, P = 0.001) earlier respectively in the ERAS group. Moreover, the rate of postoperative urinary retention (3.7% vs. 16.7%, P = 0.026) and surgical site infection (0% vs. 7.4%, P = 0.046) were significantly lower with ERAS protocol applied. CONCLUSIONS: Our study confirmed that the ERAS protocol was safe and essential for patients undergoing thoracolumbar deformity surgery for DSD. The ERAS protocol was associated with a shorter postoperative LOS, a lower rate of 90-day readmission, less rehabilitation discharge, and less postoperative complications.

ATH434 Reverses Colorectal Dysfunction in the A53T Mouse Model of Parkinson's Disease.

BACKGROUND: Gastrointestinal (GI) complications, that severely impact patient quality of life, are a common occurrence in patients with Parkinson's disease (PD). Damage to enteric neurons and the accumulation of alpha-synuclein in the enteric nervous system (ENS) are thought to contribute to this phenotype. Copper or iron chelators, that bind excess or labile metal ions, can prevent aggregation of alpha-synuclein in the brain and alleviate motor-symptoms in preclinical models of PD. OBJECTIVE: We investigated the effect of ATH434 (formally PBT434), a small molecule, orally bioavailable, moderate-affinity iron chelator, on colonic propulsion and whole gut transit in A53T alpha-synuclein transgenic mice. METHODS: Mice were fed ATH434 (30 mg/kg/day) for either 4 months (beginning at ∼15 months of age), after the onset of slowed propulsion ("treatment group"), or for 3 months (beginning at ∼12 months of age), prior to slowed propulsion ("prevention group"). RESULTS: ATH434, given after dysfunction was established, resulted in a reversal of slowed colonic propulsion and gut transit deficits in A53T mice to WT levels. In addition, ATH434 administered from 12 months prevented the slowed bead expulsion at 15 months but did not alter deficits in gut transit time when compared to vehicle-treated A53T mice. The proportion of neurons with nuclear Hu+ translocation, an indicator of neuronal stress in the ENS, was significantly greater in A53T than WT mice, and was reduced in both groups when ATH434 was administered. CONCLUSION: ATH434 can reverse some of the GI deficits and enteric neuropathy that occur in a mouse model of PD, and thus may have potential clinical benefit in alleviating the GI dysfunctions associated with PD.

Investigation of nerve pathways mediating colorectal dysfunction in Parkinson's disease model produced by lesion of nigrostriatal dopaminergic neurons.

BACKGROUND: Gastrointestinal (GI) dysfunction, including constipation, is a common non-motor symptom of Parkinson's disease (PD). The toxin 6-hydroxydopamine (6OHDA) produces the symptoms of PD, surprisingly including constipation, after it is injected into the medial forebrain bundle (MFB). However, the mechanisms involved in PD-associated constipation caused by central application of 6OHDA remain unknown. We investigated effects of 6OHDA lesioning of the MFB on motor performance and GI function. METHODS: Male Sprague Dawley rats were unilaterally injected with 6OHDA in the MFB. Colorectal propulsion was assessed by bead expulsion after 4 weeks and by recording colorectal contractions and propulsion after 5 weeks. Enteric nervous system (ENS) neuropathy was examined by immunohistochemistry. KEY RESULTS: When compared to shams, 6OHDA-lesioned rats had significantly increased times of bead expulsion from the colorectum, indicative of colon dysmotility. Administration of the colokinetic, capromorelin, that stimulates defecation centers in the spinal cord, increased the number of contractions and colorectal propulsion in both groups compared to baseline; however, the effectiveness of capromorelin in 6OHDA-lesioned rats was significantly reduced in comparison with shams, indicating that 6OHDA animals have reduced responsiveness of the spinal defecation centers. Enteric neuropathy was observed in the distal colon, revealing that lesion of the MFB has downstream effects at the cellular level, remote from the site of 6OHDA administration. CONCLUSIONS & INFERENCES: We conclude that there are trans-synaptic effects of the proximal, forebrain, lesion of pathways from the brain that send signals down the spinal cord, at the levels of the defecation centers and the ENS.

Chronic isolation stress is associated with increased colonic and motor symptoms in the A53T mouse model of Parkinson's disease.

BACKGROUND: Chronic stress exacerbates motor deficits and increases dopaminergic cell loss in several rodent models of Parkinson's disease (PD). However, little is known about effects of stress on gastrointestinal (GI) dysfunction, a common non-motor symptom of PD. We aimed to determine whether chronic stress exacerbates GI dysfunction in the A53T mouse model of PD and whether this relates to changes in α-synuclein distribution. METHODS: Chronic isolation stress was induced by single-housing WT and homozygote A53T mice between 5 and 15 months of age. GI and motor function were compared with mice that had been group-housed. KEY RESULTS: Chronic isolation stress increased plasma corticosterone and exacerbated deficits in colonic propulsion and whole-gut transit in A53T mice and also increased motor deficits. However, our results indicated that the novel environment-induced defecation response, a common method used to evaluate colorectal function, was not a useful test to measure exacerbation of GI dysfunction, most likely because of the reported reduced level of anxiety in A53T mice. A53T mice had lower corticosterone levels than WT mice under both housing conditions, but single-housing increased levels for both genotypes. Enteric neuropathy was observed in aging A53T mice and A53T mice had a greater accumulation of alpha-synuclein (αsyn) in myenteric ganglia under both housing conditions. CONCLUSIONS & INFERENCES: Chronic isolation stress exacerbates PD-associated GI dysfunction, in addition to increasing motor deficits. However, these changes in GI symptoms are not directly related to corticosterone levels, worsened enteric neuropathy, or enteric αsyn accumulation.

Muscarinic receptor 1 allosteric modulators stimulate colorectal emptying in dog, mouse and rat and resolve constipation.

BACKGROUND: Because M1 muscarinic receptors are expressed by enteric neurons, we investigated whether positive allosteric modulators of these receptors (M1PAMs) would enhance colorectal propulsion and defecation in dogs, mice, and rats. METHODS: The potencies of the M1PAMs, T662 or T523, were investigated using M1 receptor-expressing CHO cells. Effectiveness of M1PAMs on defecation was investigated by oral administration in mice and rats, by recording propulsive contractions in anaesthetized rats and by recording high amplitude propagating contractions in dogs. KEY RESULTS: PAM EC50 values in M1 receptor-expressing CHO cells were 0.7-1.8 nmol/L for T662 and 8-10 nmol/L for T523. The compounds had 1000-fold lower potencies as agonists. In anesthetized rats, both compounds elicited propulsive colorectal contractions, and in dogs, mice, and rats, oral administration increased fecal output. No adverse effects were observed in conscious animals. M1PAMs triggered propagated high amplitude contractions and caused defecation in dogs. Nerve-mediated contractions were enhanced in the isolated mouse colon. M1PAMs were equi-effective in rats with or without the pelvic nerves being severed. In two models of constipation in mice, opiate-induced constipation and constipation of aging, defecation was induced and constipation was reversed. CONCLUSION AND INFERENCES: M1PAMs act at targets sites in the colorectum to enhance colorectal propulsion. They are effective across species, and they reverse experimentally induced constipation. Previous studies have shown that they are safe in human. Because they provide an enhancement of physiological control rather than being direct agonists, they are predicted to provide effective treatment for constipation.

[Community composition and diversity of endophytic fungi from the fruits of Pteroceltis tatarinowii.] / é’æª€æžœå† ç”ŸçœŸèŒèŒç¾¤çš„ç»„æˆåŠå¤šæ ·æ€§.

Endophytic fungi from the fruit of Pteroceltis tatarinowii were studied, to understand the characteristics of microbial community composition on this ancient and peculiar wild plant. Healthy fruits were collected from areas of the natural distribution of P. tatarinowii in Langyashan Natural Reserve, Anhui Province, China. Endophytic fungi were isolated from fruit tissue, and fungal strains were classified on the basis of morphology. From 500 tissue blocks taken from fruit, a total of 428 isolates of endophytic fungi were identified and classified into 20 genera, 4 families, and 3 orders. Eighty strains showed no reproductive structures, and were classified as Mycelia sterilia (18.7%). The dominant families were Dematiaceae and Sphaeropsidaceae, occupying 38.1% and 32.9% of isolates, respectively. Alternaria and Phomopsis were the dominant genera, accounting for 27.1% and 16.8% of isolates. Different parts of the fruit had different compositions of endophytes. The highest number of fungi was isolated from seeds (19 genera, 181 strains, 42.3%), and the lowest from fruiting wings (7 genera, 88 strains, 20.6%). Alternaria was the commonest genus of endophytes, isolated from three different parts of the fruit. Phomopsis and Macrophoma were the dominant genera on carpopodium and fruiting wings, respectively. The communities on carpopodium and fruiting wings were most similar to one another (CS=0.78), while those on fruiting wings and seeds were least similar (CS=0.50). Fisher's exact test showed no significant difference between the compositions of endophytes from the carpopodium and fruiting wings, while significant diffe-rences were observed between communities on seed and carpopodium, and seed and fruiting wings.

[Species composition and ecological distribution of macrofungi in Huangpushan Natural Reserve of Anhui Province].

In order to understand and utilize the macrofungal resources in Huangpushan Natural Reserve of Anhui Province, their species composition and ecological distribution were investigated, and a comprehensive evaluation was made. A total of 87 macrofungal species were recorded, belonging to 46 genera, 22 families, 6 orders and 4 classes. They were widely distributed in broadleaf forest, coniferous forest, mixed broadleaf and coniferous forest, bamboo forest, and wasteland. According to their economic values, there were 42 edible species, 31 medicinal species, and 6 poisonous species; based on their ecological habitats, they were categorized into humicolous (44 species), lignicolous (30), ectomycorrhizal (19), and entomogenous species (2). The macro-fungi in the Reserve had great prospects of applying in food, medicine, and forestation.