bluuebunny/crossref_metadata_2025 huggingface dataset:
Surrogate fostering of mice prevents prenatal estradiol-induced insulin resistance via modulation of the microbiota-gut-brain axis
Authors: Wang Huihui , Zhou Chengliang , Gu Shuping , Sun Yun
Published: January 2023

Introduction

Prenatal and early postnatal development are known to influence future health. We previously reported that prenatal high estradiol (HE) exposure induces insulin resistance in male mice by disrupting hypothalamus development. Because a foster dam can modify a pup’s gut microbiota and affect its health later in life, we explored whether surrogate fostering could also influence glucose metabolism in HE offspring and examined mechanisms that might be involved.

Methods

We performed a surrogate fostering experiment in mice and examined the relationship between the metabolic markers associated to insulin resistance and the composition of the gut microbiota.

Results

HE pups raised by HE foster dams (HE-HE) developed insulin resistance, but HE pups fostered by negative control dams (NC-HE) did not. The gut microbiota composition of HE-HE mice differed from that of NC mice raised by NC foster dams (NC-NC), whereas the composition in NC-HE mice was similar to that of NC-NC mice. Compared with NC-NC mice, HE-HE mice had decreased levels of fecal short-chain fatty acids and serum intestinal hormones, increased food intake, and increased hypothalamic neuropeptide Y expression. In contrast, none of these indices differed between NC-HE and NC-NC mice. Spearman correlation analysis revealed a significant correlation between the altered gut microbiota composition and the insulin resistance-related metabolic indicators, indicating involvement of the microbiota-gut-brain axis.

Discussion

Our findings suggest that alterations in the early growth environment may prevent fetal-programmed glucose metabolic disorder via modulation of the microbiota-gut-brain axis. These findings offer direction for development of translational solutions for adult diseases associated with aberrant microbial communities in early life.
Effects of chlorogenic acid on growth, metabolism, antioxidation, immunity, and intestinal flora of crucian carp (Carassius auratus)
Authors: Jin Xuexia , Su Mengyuan , Liang Yunxiang , Li Yingjun
Published: January 2023

In recent years, with the harm caused by the abuse of antibiotics and the increasing demand for green and healthy food, people gradually began to look for antibiotic alternatives for aquaculture. As a Chinese herbal medicine, leaf extract chlorogenic acid (CGA) of Eucommia ulmoides Oliver can improve animal immunity and antioxidant capacity and can improve animal production performance. In this study, crucian carp (Carassius auratus) was fed with complete feed containing 200 mg/kg CGA for 60 days to evaluate the antioxidant, immuno-enhancement, and regulation of intestinal microbial activities of CGA. In comparison to the control, the growth performance indexes of CGA-added fish were significantly increased, including final body weight, weight gain rate, and specific growth rate (P < 0.01), while the feed conversion rate was significantly decreased (P < 0.01). Intestinal digestive enzyme activity significantly increased (P < 0.01); the contents of triglyceride in the liver (P < 0.01) and muscle (P > 0.05) decreased; and the expression of lipid metabolism-related genes in the liver was promoted. Additionally, the non-specific immune enzyme activities of intestinal and liver tissues were increased, but the expression level of the adenylate-activated protein kinase gene involved in energy metabolism was not affected. The antioxidant capacity of intestinal, muscle, and liver tissues was improved. Otherwise, CGA enhanced the relative abundance of intestinal microbes, Fusobacteria and Firmicutes and degraded the relative abundance of Proteobacteria. In general, our data showed that supplementation with CGA in dietary had a positive effect on Carassius auratus growth, immunity, and balance of the bacteria in the intestine. Our findings suggest that it is of great significance to develop and use CGA as a natural non-toxic compound in green and eco-friendly feed additives.
Inhibition of planktonic growth and biofilm formation of Staphylococcus aureus by entrectinib through disrupting the cell membrane
Authors: Liu Shanghong , Xiong Yanpeng , Xiao Haitao , Zheng Jinxin , Wen Zewen , Li Duoyun , Deng Qiwen , Yu Zhijian
Published: January 2023

Over the last few decades, Staphylococcus aureus infection remain a major medical challenge and health concern worldwide. Biofilm formation and antibiotic resistance caused by S. aureus make it difficult to be eradicated from bacterial infections in clinics. In this study, our data demonstrated the antibacterial and excellent anti-biofilm activity of entrectinib against S. aureus. Entrectinib also exhibited the good safety, suggesting no toxicity with antibacterial concentration of entrectinib toward the erythrocytes and mammalian 239 T cells. Moreover, entrectinib significantly reduced the bacterial burden of septic tissue in a murine model of MRSA infection. Global proteomic analysis of S. aureus treated with entrectinib showed significant changes in the expression levels of ribosomal structure-related (rpmC, rpmD, rplX, and rpsT) and oxidative stress-related proteins (Thioredoxin system), suggesting the possible inhibition of bacterial protein biosynthesis with entrectinib exposure. The increased production of reactive oxygen species (ROS) was demonstrated in the entrectinib-treated S. aureus, supported the impact of entrectinib on the expression changes of ROS-correlated proteins involved in oxidative stress. Furthermore, entrectinib-induced resistant S. aureus clone was selected by in vitro induction under entrectinib exposure and 3 amino acid mutations in the entrectinib-induced resistant S. aureus strain, 2 of which were located in the gene encoding Type II NADH: quinoneoxidoreductase and one were found in GTP pyrophosphokinase family protein. Finally, the bactericidal action of entrectinib on S. aureus were confirmed by disrupting the bacterial cell membrane. Conclusively, entrectinib exhibit the antibacterial and anti-biofilm activity by destroying cell membrane against S. aureus.
Extracellular vesicles regulate the transmission of insulin resistance and redefine noncommunicable diseases
Authors: Li Biao , Li Wan , Liu Tiancai , Zha Longying
Published: January 2023

Noncommunicable diseases (NCDs), such as diabetes and related neurological disorders, are considered to not be directly transmissible from one person to another. However, NCDs may be transmissible in vivo through extracellular vesicles (EVs). A long-term high-fat diet (HFD) can induce a series of health issues like hyperlipidemia, type 2 diabetes mellitus (T2DM), and diabetic peripheral neuropathy (DPN) due to insulin resistance. Multiple molecular signaling changes can stimulate insulin resistance, especially blocking insulin signaling by increased insulin resistance inducer (phosphorylation of negative regulatory sites of insulin receptor substrate (IRS) proteins) and decreased tyrosine phosphorylation of insulin receptor substrate (phosphorylation of positive regulatory sites of IRS), thus leading to reduced phosphorylation of AKT enzymes. Current efforts to treat T2DM and prevent its complications mainly focus on improving insulin sensitivity, enhancing insulin secretion, or supplementing exogenous insulin based on a common assumption that insulin resistance is noncommunicable. However, insulin resistance is transmissible within multiple tissues or organs throughout the body. Exploring the regulatory roles of EVs in developing insulin resistance may provide novel and effective preventive and therapeutic strategies.
Regulating Shaker Kv channel clustering by hetero-oligomerization
Authors: Nsasra Esraa , Peretz Guy , Orr Irit , Yifrach Ofer
Published: January 2023

Scaffold protein-mediated voltage-dependent ion channel clustering at unique membrane sites, such as nodes of Ranvier or the post-synaptic density plays an important role in determining action potential properties and information coding. Yet, the mechanism(s) by which scaffold protein-ion channel interactions lead to channel clustering and how cluster ion channel density is regulated are mostly unknown. This molecular-cellular gap in understanding channel clustering can be bridged in the case of the prototypical Shaker voltage-activated potassium channel (Kv), as the mechanism underlying the interaction of this channel with its PSD-95 scaffold protein partner is known. According to this mechanism, changes in the length of the intrinsically disordered channel C-terminal chain, brought about by alternative splicing to yield the short A and long B chain subunit variants, dictate affinity to PSD-95 and further controls cluster homo-tetrameric Kv channel density. These results raise the hypothesis that heteromeric subunit assembly serves as a means to regulate Kv channel clustering. Since both clustering variants are expressed in similar fly tissues, it is reasonable to assume that hetero-tetrameric channels carrying different numbers of high- (A) and low-affinity (B) subunits could assemble, thereby giving rise to distinct cluster Kv channel densities. Here, we tested this hypothesis using high-resolution microscopy, combined with quantitative clustering analysis. Our results reveal that the A and B clustering variants can indeed assemble to form heteromeric channels and that controlling the number of the high-affinity A subunits within the hetero-oligomer modulates cluster Kv channel density. The implications of these findings for electrical signaling are discussed.
Sex-dependent effects of microglial reduction on impaired fear extinction induced by single prolonged stress
Authors: Torres-Rodriguez Orlando , Ortiz-Nazario Emily , Rivera-Escobales Yesenia , Velazquez Bethzaly , Colón María , Porter James T.
Published: January 2023

Single prolonged stress (SPS) is a preclinical rodent model for studying post-traumatic stress disorder (PTSD)-like behaviors. Previously we found that increased expression of the microglial marker Iba-1 in the ventral hippocampus after SPS exposure was associated with impaired fear extinction, suggesting that microglial activity contributed to the SPS-induced behavioral changes. To test this, we examined whether reducing microglia with the colony-stimulating factor 1 receptor blocker, PLX3397, in the diet would prevent the SPS-induced extinction impairment. Male rats exposed to SPS showed enhanced fear acquisition and impaired fear extinction memory. Adding PLX3397 to the diet prevented these behavioral changes. In contrast, PLX3397 did not prevent SPS from impairing fear extinction memory in the female rats. Despite the sex-dependent behavioral effects, we found a reduced number and area fraction of Iba-1+ microglia in both male and female rats suggesting that PLX3397 had similar effects on microglia in both sexes. Altogether, these results suggest that microglia contribute to the behavioral changes induced by SPS in male but not female rats.
Realistic Actor-Critic: A framework for balance between value overestimation and underestimation
Authors: Li Sicen , Tang Qinyun , Pang Yiming , Ma Xinmeng , Wang Gang
Published: January 2023

Introduction

The value approximation bias is known to lead to suboptimal policies or catastrophic overestimation bias accumulation that prevent the agent from making the right decisions between exploration and exploitation. Algorithms have been proposed to mitigate the above contradiction. However, we still lack an understanding of how the value bias impact performance and a method for efficient exploration while keeping stable updates. This study aims to clarify the effect of the value bias and improve the reinforcement learning algorithms to enhance sample efficiency.

Methods

This study designs a simple episodic tabular MDP to research value underestimation and overestimation in actor-critic methods. This study proposes a unified framework called Realistic Actor-Critic (RAC), which employs Universal Value Function Approximators (UVFA) to simultaneously learn policies with different value confidence-bound with the same neural network, each with a different under overestimation trade-off.

Results

This study highlights that agents could over-explore low-value states due to inflexible under-overestimation trade-off in the fixed hyperparameters setting, which is a particular form of the exploration-exploitation dilemma. And RAC performs directed exploration without over-exploration using the upper bounds while still avoiding overestimation using the lower bounds. Through carefully designed experiments, this study empirically verifies that RAC achieves 10x sample efficiency and 25% performance improvement compared to Soft Actor-Critic in the most challenging Humanoid environment. All the source codes are available at https://github.com/ihuhuhu/RAC.

Discussion

This research not only provides valuable insights for research on the exploration-exploitation trade-off by studying the frequency of policies access to low-value states under different value confidence-bounds guidance, but also proposes a new unified framework that can be combined with current actor-critic methods to improve sample efficiency in the continuous control domain.
Small steps for mankind: Modeling the emergence of cumulative culture from joint active inference communication
Authors: Kastel Natalie , Hesp Casper , Ridderinkhof K. Richard , Friston Karl J.
Published: January 2023

Although the increase in the use of dynamical modeling in the literature on cultural evolution makes current models more mathematically sophisticated, these models have yet to be tested or validated. This paper provides a testable deep active inference formulation of social behavior and accompanying simulations of cumulative culture in two steps: First, we cast cultural transmission as a bi-directional process of communication that induces a generalized synchrony (operationalized as a particular convergence) between the belief states of interlocutors. Second, we cast social or cultural exchange as a process of active inference by equipping agents with the choice of who to engage in communication with. This induces trade-offs between confirmation of current beliefs and exploration of the social environment. We find that cumulative culture emerges from belief updating (i.e., active inference and learning) in the form of a joint minimization of uncertainty. The emergent cultural equilibria are characterized by a segregation into groups, whose belief systems are actively sustained by selective, uncertainty minimizing, dyadic exchanges. The nature of these equilibria depends sensitively on the precision afforded by various probabilistic mappings in each individual's generative model of their encultured niche.
Movement-specific keyboard playing for hand function in adolescents and young adults with acquired brain injury
Authors: Kim Soo Ji , Shin Yoon-Kyum , Jeong Eomhyeong , Cho Sung-Rae
Published: January 2023

Background

Patients with acquired brain injury (ABI) suffer from deficits in fine motor function in hands which affect independent self-care function in daily life. This study aimed to examine the effects of movement-specific keyboard playing for improved hand function in adolescents and young adults with ABI.

Method

A total of 23 patients with ABI participated in this study. Twelve were assigned to the intervention group and eleven to the control group. The intervention group engaged in movement-specific keyboard playing three to four times a week for 3 weeks in addition to standard care, while the control group received only standard care.

Results

The results of a mixed model of repeated measures ANOVA showed that the time effects were significant in the functional independence measure, key-pressing force, and most of the hand function tests measured. In terms of the interaction effect between group and time, a significant effect was found only in the checker-stacking task as a subtest of the Jebsen-Talyor Hand Function Test.

Discussion

These results indicate that the specified movements required to play the keyboard may involve more precise and dexterous manipulation with hands and fingers. These results also suggest that movement-specific keyboard playing has potential in optimizing the intervention effect of keyboard playing while maximizing the benefits of music for motivating young patients with ABI.
Bilateral globus pallidus interna deep brain stimulation in Parkinson’s disease: Therapeutic effects and motor outcomes prediction in a short-term follow up
Authors: Shen Dingding , Cao Linghao , Ling Yun , Li Dianyou , Ren Kang , Shi Weikun , Chen Zhonglue , Zhou Haiyan , Liu Jun
Published: January 2023

Objective

We aimed to compare the motor effect of bilateral globus pallidus interna (GPi) deep brain stimulation (DBS) on motor subtypes of Parkinson’s disease (PD) patients and identify preoperative predictive factors of short-term motor outcome.

Methods

We retrospectively investigated bilateral GPi DBS clinical outcomes in 55 PD patients in 1 year follow up. Motor outcome was measured by the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III before and 1 year after surgery. Clinical outcomes were compared among different motor subtypes. Preoperative predictors of motor outcome were assessed by performing univariate and multivariate linear regression and logistic regression analyses.

Results

At 1 year following implantation, GPi DBS significantly improved the off-medication MDS-UPDRS III scores in all motor subtype cohorts, with prominent improvement in tremor. No significant difference of postoperative motor symptoms changes was found except greater tremor improvement achieved in both the tremor-dominant (TD) and indeterminate (IND) patients compared to the postural instability and gait difficulty (PIGD) patients. High percentage of PIGD patients were weak responders to DBS. Better levodopa responsiveness and more severe tremor predicted greater overall improvement of motor function in the entire cohort. Similarly, both levodopa responsiveness and tremor improvement were confirmed as predictors for motor improvement in PIGD patients.

Conclusion

Bilateral GPi DBS could effectively improve motor outcomes in PD patients regardless of motor subtypes. Both TD and IND patients obtained larger tremor improvement. The intensity of levodopa responsiveness and the severity of tremor could serve as predictors of motor improvement 1 year after GPi DBS.
Preventive treatment response associated with migraine aura subtypes in a Thai population
Authors: Asawavichienjinda Thanin , Storer Robin James
Published: January 2023

Introduction

Some studies indicate a different response to treatment between migraine patients with and without aura.

Objectives

To determine whether aura, or simple or complex aura subtypes, are clinical markers predicting response to preventive treatment.

Methods

Conducted a retrospective cohort study at a headache clinic in a tertiary referral hospital. We included data from patients registered from 1 November 2014, to 30 June 2022, having migraine with or without aura, or with simple or complex aura, and who had received migraine preventive treatments with at least 3 months follow-up. The primary outcome was a response to preventive treatment defined as at least a 50% reduction from a baseline of monthly migraine or headache days (MMDs/MHDs). Secondary outcomes were improvement in quality of life and disability scores.

Results

For migraine patients with (45) and without (123) aura who took a migraine preventive with at least 3 months follow-up; except for median age, which was older for patients without aura, baseline sex, comorbidity, and migraine data were without significant difference including median history of migraine, chronic migraine subtype, chronic migraine with medication-overuse headache, median or mean MMDs/MHDs, number of preventive medications used, or migraine preventive medication inhibiting spreading depolarizations. Treatment outcomes at 3 and 6 months follow-up were not significantly different between migraine patients with and without aura, or with simple and complex aura, but tended to be greater in those with aura and those with complex aura. After adjustment for baseline comorbidity, migraine subtypes, aura subtypes, the number of preventives used, history of migraine, and MMDs/MHDs, we found no significant differences in 30% and 50% reduction from baseline of MMDs/MHDs in 3 or 6 months or most recent follow-up.

Conclusions

Preventive treatment response tended to be associated with migraine aura subtypes. We found preventive treatment response tended to have more favorable outcomes in those with aura, especially those with complex aura.
Modulation of the thermosensory system by oxytocin
Authors: Zayan Ugo , Caccialupi Da Prato Laura , Muscatelli Françoise , Matarazzo Valéry
Published: January 2023

Oxytocin (OT) is a neurohormone involved early in neurodevelopment and is implicated in multiple functions, including sensory modulation. Evidence of such modulation has been observed for different sensory modalities in both healthy and pathological conditions. This review summarizes the pleiotropic modulation that OT can exercise on an often overlooked sensory system: thermosensation. This system allows us to sense temperature variations and compensate for the variation to maintain a stable core body temperature. Oxytocin modulates autonomic and behavioral mechanisms underlying thermoregulation at both central and peripheral levels. Hyposensitivity or hypersensitivity for different sensory modalities, including thermosensitivity, is a common feature in autism spectrum disorder (ASD), recapitulated in several ASD mouse models. These sensory dysregulations occur early in post-natal development and are correlated with dysregulation of the oxytocinergic system. In this study, we discussed the potential link between thermosensory atypia and the dysregulation of the oxytocinergic system in ASD.
A mouse model of cone photoreceptor function loss (cpfl9) with degeneration due to a mutation in Gucy2e
Authors: Naggert Anna S. E. N. , Collin Gayle B. , Wang Jieping , Krebs Mark P. , Chang Bo
Published: January 2023

During routine screening of mouse strains and stocks by the Eye Mutant Resource at The Jackson Laboratory for genetic mouse models of human ocular disorders, we identified cpfl9, a mouse model with cone photoreceptor function loss. The mice exhibited an early-onset phenotype that was easily recognized by the absence of a cone-mediated b-wave electroretinography response and by a reduction in rod-mediated photoresponses at four weeks of age. By genetic mapping and high-throughput sequencing of a whole exome capture library of cpfl9, a homozygous 25 bp deletion within exon 11 of the Gucy2e gene was identified, which is predicted to result in a frame shift leading to premature termination. The corresponding protein in human, retinal guanylate cyclase 1 (GUCY2D), plays an important role in rod and cone photoreceptor cell function. Loss-of-function mutations in human GUCY2D cause LCA1, one of the most common forms of Leber congenital amaurosis, which results in blindness at birth or in early childhood. The early loss of cone and reduced rod photoreceptor cell function in the cpfl9 mutant is accompanied by a later, progressive loss of cone and rod photoreceptor cells, which may be relevant to understanding disease pathology in a subset of LCA1 patients and in individuals with cone-rod dystrophy caused by recessive GUCY2D variants. cpfl9 mice will be useful for studying the role of Gucy2e in the retina.
Improvement of stress adaptation and insulin resistance in women with GDM by WeChat group management during novel coronavirus pneumonia
Authors: Feng Yan , Lv Yuping , Feng Qi , Song Xinna , Li Xiaoyan , Wang Yongjun
Published: January 2023

Aim

To evaluate the improvement of glycemic control and stress adaptation in patients with GDM by mobile phone WeChat management during novel coronavirus pneumonia.

Methods

In this study, 75 women with GDM were included, of whom 35 were included in mobile WeChat group management as the GDM-M group and 40 as the GDM group.

Results

After mobile WeChat group management for 4 weeks, E and NE were lower. MDA was lower, and SOD was higher. HOMA-IR was lower. E, NE, and cortisol were related to HOMA-IR positively, MDA was positively related to HOMA-IR, and SOD was negatively related to HOMA-IR. E and cortisol were positively related to MDA but negatively related to SOD.

Conclusion

The stress adaptation disorder and insulin resistance in patients with GDM who have completed mobile WeChat group management can be improved during novel coronavirus pneumonia. Mobile WeChat management played a positive role in improving the insulin resistance of women with GDM under special circumstances, which may reduce the risk of maternal and fetal complications.
Adherence to the Dietary Approaches to Stop Hypertension diet reduces the risk of breast cancer: A systematic review and meta-analysis
Authors: Shu Long , Huang Yi-Qian , Zhang Xiao-Yan , Zheng Pei-Fen , Zhu Qin , Zhou Jian-Ying
Published: January 2023

Background

Despite increasing evidence for the association of adherence to the Dietary approaches to stop hypertension (DASH) diet with breast cancer risk, the results remain inconclusive. The purpose of the current systematic review was to summarize the evidence from previous observational studies and explore the potential association between DASH diet and breast cancer risk using meta-analysis.

Methods

A comprehensive literature search was conducted using the databases of PubMed, Web of Science, CNKI and Wanfang Data to identify the relevant publications from inception up to July 2022. The pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated for the highest versus the lowest categories of DASH score in relation to breast cancer risk, using a random-effects model. The Cochran’s Q test and I-squared (I2) statistic were used to detect the sources of heterogeneity among the included studies.

Results

Overall, eleven studies, involving 23,254 breast cancer cases and 449,273 participants, were included in this systematic review and meta-analysis. Combining 16 effect sizes from 11 studies, a significant inverse association between adherence to the DASH diet and risk of breast cancer was observed (RR = 0.79; 95% CI: 0.70, 0.90, P < 0.0001). Stratified analysis showed a significant association between adherence to the DASH diet and risk of breast cancer in case-control studies (RR = 0.49; 95% CI: 0.27–0.89, P = 0.019), and a marginally significant association in prospective cohort studies (RR = 0.92; 95% CI: 0.86–0.98, P = 0.014), respectively. Besides, a more significant association between DASH score and reduced risk of breast cancer was observed in Asian countries (RR = 0.50; 95% CI: 0.31–0.81, P = 0.005) than in the United States (RR = 0.93; 95% CI: 0.89–0.99, P = 0.012). Similarly, when we conducted analyses separately by menopausal status, we found a significant inverse association between DASH diet and breast cancer risk in postmenopausal women (RR = 0.58; 95% CI: 0.39–0.87, P = 0.008).

Conclusion

The results of this systematic review and meta-analysis indicate a significant inverse association between adherence to the DASH diet and risk of breast cancer. Further large prospective studies and randomized controlled trials are required to confirm our findings.
Efficacy and safety of bevacizumab biosimilar compared with reference bevacizumab in locally advanced and advanced non-small cell lung cancer patients: A retrospective study
Authors: Zhao Zhiting , Zhao Luqing , Xia Guohao , Lu Jianwei , Shen Bo , Zhou Guoren , Wu Fenglei , Hu Xiao , Feng Jifeng , Yu Shaorong
Published: January 2023

Background

Bevacizumab has played an important role in the systemic treatment of patients with advanced non-small-cell lung cancer (NSCLC) without gene mutation. In recent years, bevacizumab biosimilar has received marketing approval based on the results of phase III clinical studies. However, more clinical data are needed to verify the efficacy and safety of bevacizumab biosimilar in clinical application.

Materials and methods

We identified 946 patients with locally advanced or metastatic NSCLC who were treated with bevacizumab biosimilar or bevacizumab from January 1, 2019 to November 30, 2021. Comparisons and statistical analyses of bevacizumab biosimilar and bevacizumab were made in terms of efficacy and safety. Efficacy evaluation was performed directly in accordance with RECIST v1.1. Adverse events were graded following the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0.

Results

The objective response rates (ORRs) were 28.9% in the biosimilar group (n=551) and 30.9% in the reference group (n=395; unstratified ORR risk ratio: 0.934, 95% confidence interval [CI]: 0.677–1.138; unstratified ORR risk difference: −0.020, 95% CI: −0.118–0.035). The estimated median progression-free survival (mPFS) were 6.27 (95% CI: 5.53–7.01) and 4.93 (95% CI: 4.24–5.62) months in the biosimilar and reference groups, respectively (P=0.296). The number of treatment lines, combined treatment regimens and with or without radiotherapy were significant factors affecting the PFS of both groups (P<0.001, P=0.001, P=0.039). Different genetic mutations and dose intensity were not the main factors affecting PFS (P=0.627, P=0.946). The incidences of treatment-emergent adverse events (TEAEs) were 76.41% in the biosimilar group and 71.65% in the reference group (P=0.098). The incidences of grade 3 or higher TEAEs were 22.14% and 19.49% in the biosimilar and reference groups, respectively (P=0.324).

Conclusions

Bevacizumab biosimilar is equivalent in efficacy to bevacizumab in patients with locally advanced and advanced NSCLC. It showed acceptable toxicity profile and no new adverse events. Patients who were excluded by clinical trials can also benefit from bevacizumab biosimilar.
Aqueous cinnamon extract ameliorates bowel dysfunction and enteric 5-HT synthesis in IBS rats
Authors: Yu Lijuan , Huang Chunhua , Yang Wei , Ren Zhenxing , Li Lifeng , Cheng Huiyuan , Lin Chengyuan , Zhai Lixiang , Ning Ziwan , Wong Hoileong Xavier , Han Quanbin , Jia Wei , Bian Zhaoxiang , Zhao Ling
Published: January 2023

Cinnamon protects against irritable bowel syndrome with diarrhea (IBS-D) in humans, but its efficacy and underlying mechanism of action remain poorly understood. Maternally separated (MS) IBS-D rat model and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced post-inflammatory IBS-D rat model are characterized by visceral hyperalgesia and diarrhea. This study used the two models to evaluate the effect of cinnamon extract (CE) on bowel symptoms. The MS rat model was also used to explore its underlying anti-IBS mechanism. cinnamon extract reduced defecation frequency and visceral hyperalgesia in MS rats in a dose-dependent manner and effectively improved visceral hyperalgesia in TNBS rats. The efficacy of cinnamon extract was comparable to the positive drug serotonin receptor 3 (5-HT3) selective antagonist, Ramosetron. Excessive 5-HT, a well-known pathogenic factor for IBS, in the colon and circulation of IBS rats was reduced after cinnamon extract intervention. Both, gene and protein levels of the colonic 5-HT synthetase, Tryptophan Hydroxylase 1 (Tph1), were also decreased in CE-treated IBS rats. In addition, a luciferase assay revealed that cinnamon extract and its major components, catechin, procyanidin B1/2, cinnamic acid, and cinnamyl alcohol, significantly inhibited Tph1 transcription activity in vitro. These findings illustrated that aqueous cinnamon extract partially attenuated bowel symptoms in IBS models by directly inhibiting Tph1 expression and controlling 5-HT synthesis. This provides a scientific viewpoint for the use of cinnamon as a folk medication to treat IBS.
Quantitative proteomic analysis reveals the effects of mu opioid agonists on HT22 cells
Authors: Zhang Xutong , Lou Yani , Zheng Dongxu , Lu Jialin , Qi Dansi
Published: January 2023

Introduction: At present, the mu opioid receptor is the most important neuroaesthetics receptor in anesthesiology research, and the damage that it does to the nervous system is unknown.

Methods: We investigated the effects of loperamide, an agonist of the mu opioid receptor, on protein expression in HT22 cells using stable isotope labeling of amino acids in cell culture (SILAC), immobilized metal affinity chromatography (IMAC) enrichment, and high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 7,823 proteins were identified.

Results and Discussion: Bioinformatic analysis revealed that mu opioid receptor agonism can induce distinct changes in the proteome of HT22 cells. These findings improve our understanding of narcotic drugs.
The behavior of partially coherent twisted space-time beams in atmospheric turbulence
Authors: Hyde IV Milo W.
Published: January 2023

We study how atmospheric turbulence affects twisted space-time beams, which are non-stationary random optical fields whose space and time dimensions are coupled with a stochastic twist. Applying the extended Huygens–Fresnel principle, we derive the mutual coherence function of a twisted space-time beam after propagating a distance z through atmospheric turbulence of arbitrary strength. We specialize the result to derive the ensemble-averaged irradiance and discuss how turbulence affects the beam’s spatial size, pulse width, and space-time twist. Lastly, we generate, in simulation, twisted space-time beam field realizations and propagate them through atmospheric phase screens to validate our analysis.
Enhanced energy transfer in a Dicke quantum battery
Authors: Zhang Xiang , Blaauboer Miriam
Published: January 2023

We theoretically investigate the enhancement of the charging power in a Dicke quantum battery which consists of an array of N two-level systems (TLS)coupled to a single mode of cavity photons. In the limit of small N, we analytically solve the time evolution for the full charging process. The eigenvectors of the driving Hamiltonian are found to be pseudo-Hermite polynomials and the evolution is thus interpreted as harmonic oscillator like behaviour. Then we demonstrate the average charging power using a collective protocol is N times larger than that of the parallel protocol when transferring the same amount of energy. Unlike previous studies, we point out that such quantum advantage does not originate from entanglement but is due to the coherent cooperative interactions among the TLSs. Our results provide intuitive quantitative insight into the dynamic charging process of a Dicke battery and can be observed under realistic experimental conditions.
High deuteron and neutron yields from the interaction of a petawatt laser with a cryogenic deuterium jet
Authors: Jiao X. , Curry C. B. , Gauthier M. , Chou H.-G. J. , Fiuza F. , Kim J. B. , Phan D. D. , McCary E. , Galtier E. C. , Dyer G. M. , Ofori-Okai B. K. , Labun L. , Labun O. Z. , Schoenwaelder C. , Roycroft R. , Tiwari G. , Glenn G. D. , Treffert F. , Glenzer S. H. , Hegelich B. M.
Published: January 2023

A compact high-flux, short-pulse neutron source would have applications from nuclear astrophysics to cancer therapy. Laser-driven neutron sources can achieve fluxes much higher than spallation and reactor neutron sources by reducing the volume and time in which the neutron-producing reactions occur by orders of magnitude. We report progress towards an efficient laser-driven neutron source in experiments with a cryogenic deuterium jet on the Texas Petawatt laser. Neutrons were produced both by laser-accelerated multi-MeV deuterons colliding with Be and mixed metallic catchers and by d (d,n)3He fusion reactions within the jet. We observed deuteron yields of 1013/shot in quasi-Maxwellian distributions carrying ∼8−10% of the input laser energy. We obtained neutron yields greater than 1010/shot and found indications of a deuteron-deuteron fusion neutron source with high peak flux (>1022 cm−2 s−1). The estimated fusion neutron yield in our experiment is one order of magnitude higher than any previous laser-induced dd fusion reaction. Though many technical challenges will have to be overcome to convert this proof-of-principle experiment into a consistent ultra-high flux neutron source, the neutron fluxes achieved here suggest laser-driven neutron sources can support laboratory study of the rapid neutron-capture process, which is otherwise thought to occur only in astrophysical sites such as core-collapse supernova, and binary neutron star mergers.
Effects of positive end-expiratory pressure and oxygen concentration on non-hypoxemic apnea time during face mask ventilation of anesthesia induction: A randomized controlled trial
Authors: Hao Chunxiang , Ma Xiaojing , Piao Xiangmei , Fu Yunke , Ma Libin , Mi Weidong , Berra Lorenzo , Li Changtian , Zhang Changsheng
Published: January 2023

Background: The optimal ventilatory strategy for the face mask ventilation during anesthesia induction is still unknow.

Methods: We evaluated the effect of two positive end-expiratory pressure (PEEP) levels (0 cmH2O and 6 cmH2O) and two oxygen concentration levels (1.0 and .6) on non-hypoxemic apnea time during face mask ventilation of anesthesia induction. Sixty adult patients scheduled for elective surgery were enrolled in this study. The patients were randomized to receive anesthesia induction with four different ventilation strategy under volume-controlled ventilation. Patients assigned to the LOZP group received low fraction of inspiration O2 (FiO2 = .6) and 0 PEEP. Patients assigned to the LOHP group received low fraction of inspiration O2 (FiO2 = .6) and 6 cmH2O PEEP. Patients assigned to the HOZP group received high fraction of inspiration O2 (FiO2 = 1.0) and 0 PEEP. Patients assigned to the HOHP group received high fraction of inspiration O2 (FiO2 = 1.0) and 6cmH2O PEEP. After 3 min of ventilation, the patient was intubated but disconnected from the breathing circuit. Ventilation was not initiated until the pulse oximetry dropped to 90%. The primary outcome was non-hypoxemic apnea time defined as the time from cessation of ventilation to a pulse oximeter reading of 90%. The secondary outcome was the PaO2/FiO2 ratio immediately after ventilation.

Results: The non-hypoxemic apnea time was significantly longer in the group of HOHP when compared to the other three groups (192 s ± 70 s, 221 s ± 74 s, 284 s ± 101 s, and 353 s ± 85 s in the LOZP, LOHP, HOZP, and HOHP group, respectively). The PaO2/FiO2 ratio immediately after ventilation was significantly higher in the group of LOHP when compared to the other three groups (LOZP 393 ± 130, LOHP 496 ± 97, HOZP 335 ± 58, HOHP 391 ± 50). When compared the PaO2/FiO2 ratio immediately after ventilation to its value before administration of anesthesia, the PaO2/FiO2 ratio in the group of LOHP was improved, the group LOZP and HOHP remained the same, while the group HOZP significantly decreased.

Conclusion: Application of PEEP and 100% of oxygen during face mask ventilation of induction could maximize the non-hypoxemic apnea time. However, the use of PEEP and 60% of oxygen during preoxygenation resulted in improved PaO2/FiO2 ratio.
Glutathione restores the mitochondrial redox status and improves the function of the cardiovascular system in old rats
Authors: Strutynska Nataliіa , Goshovska Yulia , Mys Lidiia , Strutynskyi Ruslan , Luchkova Alina , Fedichkina Raisa , Okhai Iryna , Korkach Yuliia , Sagach Vadym
Published: January 2023

Introduction: Aging is accompanied by cardiovascular disorders which is associated with an imbalance of pro- and antioxidant systems, the mitochondrial dysfunction, etc. Glutathione (GSH) plays a critical role in protecting cells from oxidative damage. The aim of the work was to study the effect of exogenous glutathione on the redox status of mitochondria, the content of H2S and the function of the cardiovascular system in old rats.

Methods: Experiments were performed on adult (6 months) and old (24 months) Wistar rats divided into three groups: adult, old and glutathionetreated old rats. Glutathione was injected intraperitoneally at a dose of 52 mg/kg. We investigated glutathione redox balance, H2S levels, oxidative stress, the opening of the mitochondrial permeability transition pore (mPTP), the resistance of isolated heart to ischemia/reperfusion in Langendorff model, endothelium-dependent vasorelaxation of isolated aortic rings, and cardiac levels of 3-MST, CSE, and UCP3 mRNA were determined using real-time PCR analysis.

Results: Our data shows that in old rats treated with glutathione, the balance of its oxidized and reduced form changes in the direction of a significant increase (by 53.6%) of the reduced form. Glutathione pretreatment significantly increased the H2S levels, mtNOS activity, and UCP3 expression which considered as protective protein, and conversely, significantly decreased oxidative stress markers (the rate of O2•− generation, the levels of H2O2, diene conjugates and malone dialdehyde, in 2.5, 2.3, 2, and 1.6 times, respectively) in heart mitochondria. This was associated with the inhibition mitochondrial permeability transition pore opening and increased resistance of the isolated heart to ischemia/reperfusion in these animals. At the same time, in glutathione-treated old rats, we also observed restoration of endothelium-dependent vasorelaxation responses to acetylcholine, which were almost completely abolished by the NO-synthase inhibitor L-NAME.

Conclusion: Thus, the pretreatment of old rats with glutathione restores the mitochondrial redox status and improves the function of the cardiovascular system.
Indigenous and commercial isolates of arbuscular mycorrhizal fungi display differential effects in Pyrus betulaefolia roots and elicit divergent transcriptomic and metabolomic responses
Authors: Shao Yadong , Jiang Shangtao , Peng Haiying , Li Han , Li Peigen , Jiang Rou , Fang Wenyi , Chen Tingsu , Jiang Gaofei , Yang Tianjie , Nambeesan Savithri U. , Xu Yangchun , Dong Caixia
Published: January 2023

Background

Arbuscular mycorrhizal fungi (AMF) are beneficial soil fungi which can effectively help plants with acquisition of mineral nutrients and water and promote their growth and development. The effects of indigenous and commercial isolates of arbuscular mycorrhizal fungi on pear (Pyrus betulaefolia) trees, however, remains unclear.

Methods

Trifolium repens was used to propagate indigenous AMF to simulate spore propagation in natural soils in three ways: 1. the collected soil was mixed with fine roots (R), 2. fine roots were removed from the collected soil (S), and 3. the collected soil was sterilized with 50 kGy 60Co γ-radiation (CK). To study the effects of indigenous AMF on root growth and metabolism of pear trees, CK (sterilized soil from CK in T. repens mixed with sterilized standard soil), indigenous AMF (R, soil from R in T. repens mixed with sterilized standard soil; S, soil from S in T. repens mixed with sterilized standard soil), and two commercial AMF isolates (Rhizophagus intraradices(Ri) and Funneliformis mosseae (Fm)) inoculated in the media with pear roots. Effects on plant growth, root morphology, mineral nutrient accumulation, metabolite composition and abundance, and gene expression were analyzed.

Results

AMF treatment significantly increased growth performance, and altered root morphology and mineral nutrient accumulation in this study, with the S treatment displaying overall better performance. In addition, indigenous AMF and commercial AMF isolates displayed common and divergent responses on metabolite and gene expression in pear roots. Compared with CK, most types of flavones, isoflavones, and carbohydrates decreased in the AMF treatment, whereas most types of fatty acids, amino acids, glycerolipids, and glycerophospholipids increased in response to the AMF treatments. Further, the relative abundance of amino acids, flavonoids and carbohydrates displayed different trends between indigenous and commercial AMF isolates. The Fm and S treatments altered gene expression in relation to root metabolism resulting in enriched fructose and mannose metabolism (ko00051), fatty acid biosynthesis (ko00061) and flavonoid biosynthesis (ko00941).

Conclusions

This study demonstrates that indigenous AMF and commercial AMF isolates elicited different effects in pear plants through divergent responses from gene transcription to metabolite accumulation.
Exploiting photosynthesis-driven P450 activity to produce indican in tobacco chloroplasts
Authors: Mellor Silas B. , Behrendorff James B. Y. H. , Ipsen Johan Ø. , Crocoll Christoph , Laursen Tomas , Gillam Elizabeth M. J. , Pribil Mathias
Published: January 2023

Photosynthetic organelles offer attractive features for engineering small molecule bioproduction by their ability to convert solar energy into chemical energy required for metabolism. The possibility to couple biochemical production directly to photosynthetic assimilation as a source of energy and substrates has intrigued metabolic engineers. Specifically, the chemical diversity found in plants often relies on cytochrome P450-mediated hydroxylations that depend on reductant supply for catalysis and which often lead to metabolic bottlenecks for heterologous production of complex molecules. By directing P450 enzymes to plant chloroplasts one can elegantly deal with such redox prerequisites. In this study, we explore the capacity of the plant photosynthetic machinery to drive P450-dependent formation of the indigo precursor indoxyl-β-D-glucoside (indican) by targeting an engineered indican biosynthetic pathway to tobacco (Nicotiana benthamiana) chloroplasts. We show that both native and engineered variants belonging to the human CYP2 family are catalytically active in chloroplasts when driven by photosynthetic reducing power and optimize construct designs to improve productivity. However, while increasing supply of tryptophan leads to an increase in indole accumulation, it does not improve indican productivity, suggesting that P450 activity limits overall productivity. Co-expression of different redox partners also does not improve productivity, indicating that supply of reducing power is not a bottleneck. Finally, in vitro kinetic measurements showed that the different redox partners were efficiently reduced by photosystem I but plant ferredoxin provided the highest light-dependent P450 activity. This study demonstrates the inherent ability of photosynthesis to support P450-dependent metabolic pathways. Plants and photosynthetic microbes are therefore uniquely suited for engineering P450-dependent metabolic pathways regardless of enzyme origin. Our findings have implications for metabolic engineering in photosynthetic hosts for production of high-value chemicals or drug metabolites for pharmacological studies.