Parvalbumin and Somatostatin: Biomarkers for Two Parallel Tectothalamic Pathways in the Auditory Midbrain.

The inferior colliculus (IC) represents a crucial relay station in the auditory pathway, located in the midbrain's tectum and primarily projecting to the thalamus. Despite the identification of distinct cell classes based on various biomarkers in the IC, their specific contributions to the organization of auditory tectothalamic pathways have remained poorly understood. In this study, we demonstrate that IC neurons expressing parvalbumin (ICPV+) or somatostatin (ICSOM+) represent two minimally overlapping cell classes throughout the three IC subdivisions in mice of both sexes. Strikingly, regardless of their location within the IC, these neurons predominantly project to the primary and secondary auditory thalamic nuclei, respectively. Cell class-specific input tracing suggested that ICPV+ neurons primarily receive auditory inputs, whereas ICSOM+ neurons receive significantly more inputs from the periaqueductal gray and the superior colliculus (SC), which are sensorimotor regions critically involved in innate behaviors. Furthermore, ICPV+ neurons exhibit significant heterogeneity in both intrinsic electrophysiological properties and presynaptic terminal size compared with ICSOM+ neurons. Notably, approximately one-quarter of ICPV+ neurons are inhibitory neurons, whereas all ICSOM+ neurons are excitatory neurons. Collectively, our findings suggest that parvalbumin and somatostatin expression in the IC can serve as biomarkers for two functionally distinct, parallel tectothalamic pathways. This discovery suggests an alternative way to define tectothalamic pathways and highlights the potential usefulness of Cre mice in understanding the multifaceted roles of the IC at the circuit level.

Transcriptome-wide profiling of A-to-I RNA editing by Slic-seq.

Adenosine-to-inosine (A-to-I) RNA editing is a post-transcriptional processing event involved in diversifying the transcriptome and is responsible for various biological processes. In this context, we developed a new method based on the highly selective cleavage activity of Endonuclease V against Inosine and the universal activity of sodium periodate against all RNAs to enrich the inosine-containing RNA and accurately identify the editing sites. We validated the reliability of our method in human brain in both Alu and non-Alu elements. The conserved sites of A-to-I editing in human cells (HEK293T, HeLa, HepG2, K562 and MCF-7) primarily occurs in the 3'UTR of the RNA, which are highly correlated with RNA binding and protein binding. Analysis of the editing sites between the human brain and mouse brain revealed that the editing of exons is more conserved than that in other regions. This method was applied to three neurological diseases (Alzheimer's, epilepsy and ageing) of mouse brain, reflecting that A-to-I editing sites significantly decreased in neuronal activity genes.

PIEZO2 mediates ultrasonic hearing via cochlear outer hair cells in mice.

Ultrasonic hearing and vocalization are the physiological mechanisms controlling echolocation used in hunting and navigation by microbats and bottleneck dolphins and for social communication by mice and rats. The molecular and cellular basis for ultrasonic hearing is as yet unknown. Here, we show that knockout of the mechanosensitive ion channel PIEZO2 in cochlea disrupts ultrasonic- but not low-frequency hearing in mice, as shown by audiometry and acoustically associative freezing behavior. Deletion of Piezo2 in outer hair cells (OHCs) specifically abolishes associative learning in mice during hearing exposure at ultrasonic frequencies. Ex vivo cochlear Ca2+ imaging has revealed that ultrasonic transduction requires both PIEZO2 and the hair-cell mechanotransduction channel. The present study demonstrates that OHCs serve as effector cells, combining with PIEZO2 as an essential molecule for ultrasonic hearing in mice.

A retrospective study on the relationship between serum electrolyte disorder and delayed cerebral infarction after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Delayed cerebral ischemia (DCI)-induced cerebral infarction is a major cause of adverse neurological outcomes following aneurysmal subarachnoid hemorrhage (aSAH). This study aimed to investigate the relationship between postoperative serum electrolyte levels and DCI in patients with aSAH. MATERIALS AND METHODS: We analyzed the data of patients with aSAH between 2015 and 2022. The patients were classified into two groups according to whether they experienced DCI. Electrolyte levels were categorized into three groups based on the normal ranges for electrolytes. Logistic regression models were used to study the relationship between electrolyte levels and DCI. Another logistic regression analysis was conducted to explore the relationship between the different severity levels of statistically significant indicators and DCI. A restrictive cubic spline model was adopted to assess the potential linear relationship between electrolytes and DCI. Subsequently, sensitivity analysis was performed to assess the impact of collinearity among ions. Finally, subgroup analysis was performed. RESULTS: This study included 1,099 patients. Patients with hyperchloremia were more prone to DCI than those with normal chloride levels. Subsequently, excluding the population with hypochloremia, both mild and severe hyperchloremia were found to be associated with an increased risk of DCI compared with normal chloride levels. Within the framework of a restrictive cubic spline, our findings revealed an increased incidence of DCI (P for nonlinear = 0.735) as chloride levels increased. Sensitivity analysis revealed that patients with severe hyperchloremia were more susceptible to DCI. CONCLUSIONS: This study found that patients with aSAH and postoperative hyperchloremia are more prone to developing DCI.

A comprehensive analysis of patients with cerebral arteriovenous malformation with headache: assessment of risk factors and treatment effectiveness.

BACKGROUND: Due to the high mortality and disability rate of intracranial hemorrhage, headache is not the main focus of research on cerebral arteriovenous malformation (AVM), so research on headaches in AVM is still scarce, and the clinical understanding is shallow. This study aims to delineate the risk factors associated with headaches in AVM and to compare the effectiveness of various intervention treatments versus conservative treatment in alleviating headache symptoms. METHODS: This study conducted a retrospective analysis of AVMs who were treated in our institution from August 2011 to December 2021. Multivariable logistic regression analysis was employed to assess the risk factors for headaches in AVMs with unruptured, non-epileptic. Additionally, the effectiveness of different intervention treatments compared to conservative management in alleviating headaches was evaluated through propensity score matching (PSM). RESULTS: A total of 946 patients were included in the analysis of risk factors for headaches. Multivariate logistic regression analysis identified that female (OR 1.532, 95% CI 1.173-2.001, p = 0.002), supply artery dilatation (OR 1.423, 95% CI 1.082-1.872, p = 0.012), and occipital lobe (OR 1.785, 95% CI 1.307-2.439, p < 0.001) as independent risk factors for the occurrence of headaches. There were 443 AVMs with headache symptoms. After propensity score matching, the microsurgery group (OR 7.27, 95% CI 2.82-18.7 p < 0.001), stereotactic radiosurgery group(OR 9.46, 95% CI 2.26-39.6, p = 0.002), and multimodality treatment group (OR 8.34 95% CI 2.87-24.3, p < 0.001) demonstrate significant headache relief compared to the conservative group. However, there was no significant difference between the embolization group (OR 2.24 95% CI 0.88-5.69, p = 0.091) and the conservative group. CONCLUSIONS: This study identified potential risk factors for headaches in AVMs and found that microsurgery, stereotactic radiosurgery, and multimodal therapy had significant benefits in headache relief compared to conservative treatment. These findings provide important guidance for clinicians when developing treatment options that can help improve overall treatment outcomes and quality of life for patients.

The micro-pathological characteristics in cerebral arteriovenous malformations(cAVMs).

BACKGROUND: Rupture and hemorrhage is the most serious complication of cerebral arteriovenous malformation(cAVMs), and have a significant impact on quality of life. OBJECTIVES: We investigated the hematoxylin and eosin staining and ultrastructural features of cAVMs and characterized the abnormal vascular structure of cAVMs. METHODS: Light and electron microscopy were performed on a series of pathological specimens obtained from 12 patients with cAVMs who underwent surgical resection for the first time without radiosurgery or embolization therapy. RESULTS: In tunica intima, we found that the vascular endothelial cells of cAVMs were damaged, and the lysis of the cell body occurred in multiple regions. In tunica media, the arrangement of the elastic layer was disordered, and the thickness was uneven. Part of the structure of the elastic lamina was missing. The part of tunica adventitia was fractured and discontinuous. In addition, we also observed the phenomenon that different blood vessels share the same vascular wall. Macrophage phagocytosis and lymphocyte infiltration in the adventitial region of ruptured cAVMs. Abnormal lipid deposition in vascular endothelial cells and smooth muscle cells. CONCLUSIONS: The structural incompleteness of cAVMs may be an important cause of hemorrhage.

Elevated blood hemoglobin on admission as an independent predictor of unfavorable outcomes in patients with aneurysmal subarachnoid hemorrhage.

Hemoglobin (HGB), a potent spasmogen, may cause irreversible damage to the brain after aneurysm rupture. However, there is no clinical evidence to reveal the relationship between blood HGB concentrations on admission and the prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH). We retrospectively reviewed all aSAH patients admitted to our institution between January 2015 and December 2020. Functional outcome was assessed at 90 days after discharge using the modified Rankin scale (mRS). Independent risk factors associated with 90-day unfavorable outcomes were derived from a forward stepwise multivariate analysis. Receiver operating characteristic curve analysis was conducted to identify the best cutoff value of HGB to discriminate 90-day unfavorable outcomes. Then, patients were divided into two groups according to the cutoff value of HGB, and to account for imbalances in baseline characteristics, propensity score matching (PSM) was carried out to assess the impact of HGB on in-hospital complications. A total of 800 aSAH patients without anemia on admission were retrospectively enrolled in this study. Elevated blood HGB (OR = 1.02, 95% CI = 1.00-1.03, p = 0.018) on admission was identified as an independent risk factor associated with 90-day unfavorable outcomes, and the cutoff value was 149.5 g/L. After PSM, patients with an HGB > 149.5 g/L had a higher incidence of in-hospital delayed cerebral ischemia (DCI) (33.9% vs. 22.0%, p = 0.013) and deep vein thrombosis (DVT) (11.9% vs. 4.0%, p = 0.006). Patients with a blood HGB > 149.5 g/L on admission might develop more DCI and DVT during hospitalization, leading to 90-day unfavorable outcomes in aSAH patients. ClinicalTrials.gov Identifier: NCT04785976. 2021/03/05, retrospectively registered.

The effect of sex differences on complications and 90-day outcomes after aneurysmal subarachnoid hemorrhage: a propensity score-matched analysis.

Aneurysmal subarachnoid hemorrhage (aSAH) is the most devastating form of stroke. Up to now, little is known about the effect of sex differences on complications and outcomes. We retrospectively reviewed aSAH patients admitted to our institution between January 2015 and December 2020. The functional outcomes at discharge and 90 days after discharge were assessed using the modified Rankin Scale (mRS). Baseline characteristics, in-hospital complications, and outcomes were compared after 1:1 propensity score matching (PSM). The area under the curve (AUC) in the receiver operating characteristic curve (ROC) analysis was calculated to measure each independent risk factor's prediction ability. A total of 833 patients were included. After PSM, 109 male patients were compared with 109 female patients. Female patients had a higher incidence of anemia (47/109 [43.1%] vs. 30/109 [27.5%], p = 0.016) than male patients, while male patients had a higher incidence of pneumonia (36/109 [33.0%] vs. 19/109 [17.4%], p = 0.008) than female patients. No significant differences were found in the rate of unfavorable outcomes at discharge and 90-day outcomes (40/109 [36.7%] vs. 50/109 [45.9%], p = 0.169; 15/109 [13.8%] vs. 19/107 [17.8%], p = 0.420) between female and male patients. Pneumonia (AUC = 0.749, 95% confidence interval [CI] = 0.623-0.875, p < 0.001) and anemia (AUC = 0.753, 95% CI = 0.632-0.873, p = 0.002) showed good ability to predict 90-day unfavorable outcomes in male and female patients, respectively. Female patients had a higher incidence of anemia but a lower incidence of pneumonia during hospitalization. However, differences in in-hospital complications did not result in differences in outcomes between women and men. Clinical Trial Registration: NCT04785976. 2021/03/05, retrospectively registered.

Estimating Regional Methane Emission Factors from Energy and Agricultural Sector Sources Using a Portable Measurement System: Case Study of the Denver-Julesburg Basin.

Methane (CH4), a powerful greenhouse gas (GHG), has been identified as a key target for emission reduction in the Paris agreement, but it is not currently clear where efforts should be focused to make the greatest impact. Currently, activity data and standard emission factors (EF) are used to generate GHG emission inventories. Many of the EFs are globally uniform and do not account for regional variability in industrial or agricultural practices and/or regulation. Regional EFs can be derived from top-down emissions measurements and used to make bespoke regional GHG emission inventories that account for geopolitical and social variability. However, most large-scale top-down approaches campaigns require significant investment. To address this, lower-cost driving surveys (DS) have been identified as a viable alternative to more established methods. DSs can take top-down measurements of many emission sources in a relatively short period of time, albeit with a higher uncertainty. To investigate the use of a portable measurement system, a 2260 km DS was conducted throughout the Denver-Julesburg Basin (DJB). The DJB covers an area of 8000 km2 north of Denver, CO and is densely populated with CH4 emission sources, including oil and gas (O and G) operations, agricultural operations (AGOs), lakes and reservoirs. During the DS, 157 individual CH4 emission sources were detected; 51%, 43% and 4% of sources were AGOs, O and G operations, and natural sources, respectively. Methane emissions from each source were quantified using downwind concentration and meteorological data and AGOs and O and G operations represented nearly all the CH4 emissions in the DJB, accounting for 54% and 37% of the total emission, respectively. Operations with similar emission sources were grouped together and average facility emission estimates were generated. For agricultural sources, emissions from feedlot cattle, dairy cows and sheep were estimated at 5, 31 and 1 g CH4 head-1 h-1, all of which agreed with published values taken from focused measurement campaigns. Similarly, for O and G average emissions for well pads, compressor stations and gas processing plants (0.5, 14 and 110 kg CH4 facility-1 h-1) were in reasonable agreement with emission estimates from intensive measurement campaigns. A comparison of our basin wide O and G emissions to measurements taken a decade ago show a decrease of a factor of three, which can feasibly be explained by changes to O and G regulation over the past 10 years, while emissions from AGOs have remained constant over the same time period. Our data suggest that DSs could be a low-cost alternative to traditional measurement campaigns and used to screen many emission sources within a region to derive representative regionally specific and time-sensitive EFs. The key benefit of the DS is that many regions can be screened and emission reduction targets identified where regional EFs are noticeably larger than the regional, national or global averages.

Distinct Manifestations of Cooperative, Multidimensional Stimulus Representations in Different Auditory Forebrain Stations.

Classic spectrotemporal receptive fields (STRFs) for auditory neurons are usually expressed as a single linear filter representing a single encoded stimulus feature. Multifilter STRF models represent the stimulus-response relationship of primary auditory cortex (A1) neurons more accurately because they can capture multiple stimulus features. To determine whether multifilter processing is unique to A1, we compared the utility of single-filter versus multifilter STRF models in the medial geniculate body (MGB), anterior auditory field (AAF), and A1 of ketamine-anesthetized cats. We estimated STRFs using both spike-triggered average (STA) and maximally informative dimension (MID) methods. Comparison of basic filter properties of first maximally informative dimension (MID1) and second maximally informative dimension (MID2) in the 3 stations revealed broader spectral integration of MID2s in MGBv and A1 as opposed to AAF. MID2 peak latency was substantially longer than for STAs and MID1s in all 3 stations. The 2-filter MID model captured more information and yielded better predictions in many neurons from all 3 areas but disproportionately more so in AAF and A1 compared with MGBv. Significantly, information-enhancing cooperation between the 2 MIDs was largely restricted to A1 neurons. This demonstrates significant differences in how these 3 forebrain stations process auditory information, as expressed in effective and synergistic multifilter processing.

Distinct Anatomical Connectivity Patterns Differentiate Subdivisions of the Nonlemniscal Auditory Thalamus in Mice.

Systematic examination of the inputs and outputs of the nonlemniscal auditory thalamus will facilitate the functional elucidation of this complex structure in the central auditory system. In mice, comprehensive tracing studies that reveal the long-range connectivity of the nonlemniscal auditory thalamus are lacking. To this end, we used Cre-inducible anterograde and monosynaptic retrograde viruses in Calbindin-2A-dgCre-D and Calretinin-IRES-Cre mice, focusing on the differences across subdivisions of the nonlemniscal auditory thalamus. We found that, 1) the dorsal and medial parts of the auditory thalamus were predominantly connected to sensory processing centers, whereas the posterior intralaminar (PIN) and peripeduncular nucleus (PP) were additionally connected to emotion and motivation modulation centers; 2) ventral auditory cortical areas were the major source of cortical inputs for all subdivisions, and the PIN/PP received more inputs from cortical layer 5 than other subdivisions did; 3) deep layers of the superior colliculus and rostral part of the nonlemniscal inferior colliculus preferentially projected to the PIN/PP; and 4) compared with the dorsal auditory thalamus, the PIN/PP mainly innervated association cortices. In addition, new brain areas connected to the nonlemniscal auditory thalamus, mostly the PIN/PP, were identified. Our results suggested subdivision-specific function of the nonlemniscal auditory thalamus in sound processing.

Fast Inhibitory Decay Facilitates Adult-like Temporal Processing in Layer 5 of Developing Primary Auditory Cortex.

The protracted maturational process of temporal processing in layer 4 (L4) of primary auditory cortex (A1) has been extensively studied. Accumulating evidences show that layer 5 (L5) receives direct thalamic inputs as well. How the temporal responses in L5 may developmentally emerge remains unclear. Using in vivo loose-patch recordings in rat A1, we found that putative pyramidal (Pyr) neurons in developing L5 exhibited adult-like stimulus-following ability but less bursting shortly after hearing onset. L5 Pyr neurons in adult A1 exhibited phase-locking similar to L4 neurons, while L5 fast-spiking (FS) neurons showed greater phase-locking at 7 and 12.5 pps. In developing L5, whole-cell recordings revealed inhibition with decay constant comparable to that in adult L5, thereby avoiding the summation of inhibition that contributed to the strong adaptation in L4. Given the targets of L5 outputs, the relatively precocious temporal processing in L5 might contribute to temporal response maturation in connected cortical and subcortical areas. Our findings were in agreement with the idea that L5 may be a "hub" for processing cortical inputs and outputs that can operate independently of L4.

A Critical Role of Inhibition in Temporal Processing Maturation in the Primary Auditory Cortex.

Faithful representation of sound envelopes in primary auditory cortex (A1) is vital for temporal processing and perception of natural sounds. However, the emergence of cortical temporal processing mechanisms during development remains poorly understood. Although cortical inhibition has been proposed to play an important role in this process, direct in-vivo evidence has been lacking. Using loose-patch recordings in rat A1 immediately after hearing onset, we found that stimulus-following ability in fast-spiking neurons was significantly better than in regular-spiking (RS) neurons. In-vivo whole-cell recordings of RS neurons revealed that inhibition in the developing A1 demonstrated much weaker adaptation to repetitive stimuli than in adult A1. Furthermore, inhibitory synaptic inputs were of longer duration than observed in vitro and in adults. Early in development, overlap of the prolonged inhibition evoked by 2 closely following stimuli disrupted the classical temporal sequence between excitation and inhibition, resulting in slower following capacity. During maturation, inhibitory duration gradually shortened accompanied by an improving temporal following ability of RS neurons. Both inhibitory duration and stimulus-following ability demonstrated exposure-based plasticity. These results demonstrate the role of inhibition in setting the pace for experience-dependent maturation of temporal processing in the auditory cortex.

Developmental sensory experience balances cortical excitation and inhibition.

Early in life, neural circuits are highly susceptible to outside influences. The organization of the primary auditory cortex (A1) in particular is governed by acoustic experience during the critical period, an epoch near the beginning of postnatal development throughout which cortical synapses and networks are especially plastic. This neonatal sensitivity to the pattern of sensory inputs is believed to be essential for constructing stable and adequately adapted representations of the auditory world and for the acquisition of language skills by children. One important principle of synaptic organization in mature brains is the balance between excitation and inhibition, which controls receptive field structure and spatiotemporal flow of neural activity, but it is unknown how and when this excitatory-inhibitory balance is initially established and calibrated. Here we use whole-cell recording to determine the processes underlying the development of synaptic receptive fields in rat A1. We find that, immediately after the onset of hearing, sensory-evoked excitatory and inhibitory responses are equally strong, although inhibition is less stimulus-selective and mismatched with excitation. However, during the third week of postnatal development, excitation and inhibition become highly correlated. Patterned sensory stimulation drives coordinated synaptic changes across receptive fields, rapidly improves excitatory-inhibitory coupling and prevents further exposure-induced modifications. Thus, the pace of cortical synaptic receptive field development is set by progressive, experience-dependent refinement of intracortical inhibition.

Serum antibody against Helicobacter pylori FlaA and risk of gastric cancer.

BACKGROUND: Helicobacter pylori (H. pylori) infection is a major risk factor for gastric cancer (GC); however, only a minority of infected individuals develops GC. We aim to assess the association between serostatus of antibody against H. pylori flagellin A (FlaA) and risk of GC and to evaluate the value of serum FlaA antibody as a novel screening biomarker for GC risk. METHODS: A hospital-based case-control study including 232 cases and 264 controls was conducted. Logistic regression was adopted to analyze the association between the serostatus of FlaA antibody and risk of GC. Serum FlaA antibody was measured by an enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve was used to evaluate the screening efficacy and to identify a cutoff point of serum FlaA antibody level. RESULTS: Helicobacter pylori infection was associated with an increased risk of GC (p = .007). A positive association between serum FlaA antibody and GC risk was observed in overall subjects and H. pylori-positive subjects (OR [95% CI]: 6.8 [4.3-10.7] and 6.9 [3.6-13.4], respectively; p < .001). The seropositivity of FlaA antibody was strongly related to GC risk in a dose-dependent manner (p for trend < .001). The optimal cutoff value (OD) was 0.1403, providing a sensitivity of 74.1% and a specificity of 64.4%. The area under the ROC curve (AUC) was 0.74 in overall subjects and 0.73 in H. pylori-positive subjects, respectively. CONCLUSIONS: FlaA was an independent risk factor for H. pylori-related GC. Serum FlaA antibody may serve as a novel noninvasive biomarker for early detection of GC.

The "spillover effect" of long-term care insurance in China on spouses' health and well-being.

This study examined the spillover effect of long-term care insurance (LTCI) on the health outcomes and well-being of spouses for Chinese middle and old-aged adults with expected LTC demand or actual care burdens. Using panel data from the China Health and Retirement Longitudinal Study between 2011 and 2018, we investigated the impact of the introduction of LTCI pilots across several cities on old individuals by using the difference-in-differences (DID) approach. We found a spillover effect of LTCI on the health and well-being outcomes of spouses of middle and old-aged individuals with functional limitations. It might due to the fact that LTCI could relieve economic burden by reducing out-of-pocket medical expenditures, which further affects health and well-being of spouses. The spillover effect on health and well-being was found to be stronger for male spouses and low-educated spouses. Spouses of the individuals aged below 80 years old and those live without adult children were more likely to benefit from the introduction of LTCI. Moreover, providing combination benefits seems to make spouses better off than offering direct services. Therefore, the results implied that the expansion of LTCI not only helped the care recipients themselves but could also improve the health and well-being of the spouses of functionally impaired older adults.

An Audio-Visual Speech Separation Model Inspired by Cortico-Thalamo-Cortical Circuits.

Audio-visual approaches involving visual inputs have laid the foundation for recent progress in speech separation. However, the optimization of the concurrent usage of auditory and visual inputs is still an active research area. Inspired by the cortico-thalamo-cortical circuit, in which the sensory processing mechanisms of different modalities modulate one another via the non-lemniscal sensory thalamus, we propose a novel cortico-thalamo-cortical neural network (CTCNet) for audio-visual speech separation (AVSS). First, the CTCNet learns hierarchical auditory and visual representations in a bottom-up manner in separate auditory and visual subnetworks, mimicking the functions of the auditory and visual cortical areas. Then, inspired by the large number of connections between cortical regions and the thalamus, the model fuses the auditory and visual information in a thalamic subnetwork through top-down connections. Finally, the model transmits this fused information back to the auditory and visual subnetworks, and the above process is repeated several times. The results of experiments on three speech separation benchmark datasets show that CTCNet remarkably outperforms existing AVSS methods with considerably fewer parameters. These results suggest that mimicking the anatomical connectome of the mammalian brain has great potential for advancing the development of deep neural networks.

Cross-talk of MLST and transcriptome unveiling antibiotic resistance mechanism of carbapenem resistance Acinetobacter baumannii clinical strains isolated in Guiyang, China.

Introduction: Acinetobacter baumannii (A. baumannii) is an important opportunistic pathogen causing nosocomial infection in the clinic. The occurrence rate of antibiotic resistance is increasing year by year, resulting in a highly serious situation of bacterial resistance. Methods: To better understand the local epidemiology of multidrug-resistant A. baumannii, an investigation was conducted on the antibiotic resistance of different types of A. baumannii and its relationship with the genes of A. baumannii. Furthermore, the molecular mechanism underlying antibiotic resistance in A. baumannii was investigated through transcriptome analysis. Results: These results showed that a total of 9 STs were detected. It was found that 99% of the strains isolated in the hospital belonged to the same STs, and the clone complex CC208 was widely distributed in various departments and all kinds of samples. Furthermore, these A. baumannii strains showed high resistance to ertapenem, biapenem, meropenem, and imipenem, among which the resistance to ertapenem was the strongest. The detection rate of bla OXA-51 gene in these carbapenem resistance A. baumannii (CRAB) reached 100%; Additionally, the transcriptome results showed that the resistance genes were up-regulated in resistance strains, and these genes involved in biofilm formation, efflux pumps, peptidoglycan biosynthesis, and chaperonin synthesis. Discussion: These results suggest that the CC208 STs were the main clonal complex, and showed high carbapenem antibiotic resistance. All these resistant strains were distributed in various departments, but most of them were distributed in intensive care units (ICU). The bla OXA-23 was the main antibiotic resistance genotype; In summary, the epidemic trend of clinical A. baumannii in Guiyang, China was analyzed from the molecular level, and the resistance mechanism of A. baumannii to carbapenem antibiotics was analyzed with transcriptome, which provided a theoretical basis for better control of A. baumannii.

Elucidating causal relationships of diet-derived circulating antioxidants and the risk of osteoporosis: A Mendelian randomization study.

Background: Osteoporosis (OP) is typically diagnosed by evaluating bone mineral density (BMD), and it frequently results in fractures. Here, we investigated the causal relationships between diet-derived circulating antioxidants and the risk of OP using Mendelian randomization (MR). Methods: Published studies were used to identify instrumental variables related to absolute levels of circulating antioxidants like lycopene, retinol, ascorbate, and ß-carotene, as well as antioxidant metabolites such as ascorbate, retinol, α-tocopherol, and γ-tocopherol. Outcome variables included BMD (in femoral neck, lumbar spine, forearm, heel, total body, total body (age over 60), total body (age 45-60), total body (age 30-45), total body (age 15-30), and total body (age 0-15)), fractures (in arm, spine, leg, heel, and osteoporotic fractures), and OP. Inverse variance weighted or Wald ratio was chosen as the main method for MR analysis based on the number of single nucleotide polymorphisms (SNPs). Furthermore, we performed sensitivity analyses to confirm the reliability of the findings. Results: We found a causal relationship between absolute retinol levels and heel BMD (p = 7.6E-05). The results of fixed effects IVW showed a protective effect of absolute retinol levels against heel BMD, with per 0.1 ln-transformed retinol being associated with a 28% increase in heel BMD (OR: 1.28, 95% CI: 1.13-1.44). In addition, a sex-specific effect of the absolute circulating retinol levels on the heel BMD has been observed in men. No other significant causal relationship was found. Conclusion: There is a positive causal relationship between absolute retinol levels and heel BMD. The implications of our results should be taken into account in future studies and in the creation of public health policies and OP prevention tactics.

Molecular characterization and antimicrobial activity of cecropin family in Hermetia illucens.

Antimicrobial peptides are potential alternatives to traditional antibiotics in the face of increasing bacterial resistance. Insects possess many antimicrobial peptides and have become a valuable source of novel and highly effective antimicrobial peptides. Hermetia illucens as a resource insect, for example, has the highest number of antimicrobial peptides of any dipteran. However, most antimicrobial peptides, especially cecropin, have not been comprehensively identified and have not been evaluated for their antimicrobial ability. In this study, we analyzed the localization and gene structure of 33 cecropin molecules in the H. illucens genome and evaluated their activity against common human pathogens. The results showed that 32 cecropin molecules were concentrated on 1 chromosome, most with 2 exons. More importantly, most of the cecropins had a good antibacterial effect against Gram-negative bacteria, and were not hemolytic. The minimum inhibitory concentration (MIC) of the cecropin designated H3 against E. coli was 4 µg/mL. The toxicity, killing time kinetics, and anti-biofilm activity of H3 were further investigated and confirmed its antimicrobial ability. Overall, H3 is a potential candidate for the development of new antimicrobials to treat severe infections caused by Gram-negative pathogens such as E. coli.