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جهة العمل : رواية /
بدأ \"جهة العمل\" بتوزيع الكمثرى بمناسبة عيد العمال. وتنتهي أيضا بتوزيع الكمثرى، وأيضا بمناسبة عيد العمال. وما بين الكمثرى الأولى \"العطية\" والثانية \"السليمة\"، تدور أحداث الرواية. يرصد الكاتب ليو جين يون في عام واحد بالضبط، أحوال ستة من الموظفين يعملون معا في جهة عمل واحدة؛ شياو لين، لاو تشانغ، لاو سوين، لاو تشياو، وشياو بنغ، ولاو خير ، كل واحد فيهم عالم قائم بذاته، كل له تطلعاته الوظيفية التي يسعى إليها بكل ما أوتي من سبل باستثناء شياو بنغ التي لا تصارع على ترقية ولا تبالي بأحد. يرتفع الحظ بأحدهم فيترقى، ويخون الحظ آخر فيبقى حيث هو، وهو قاب قوسين أو أدنى من الترقية. صراعات أراها بعين القرن الواحد والعشرين ساذجة إلى حد كبير، فالصراعات في زماننا أشد ضراوة بكثير مما كانت عليه في ثمانينيات القرن الماضي. ولكن يبقى أن الرواية ترصد فترة لا نعرف نحن عنها الشيء الكثير. وترسم بعض ملامح الثقافة الصينية آنذاك. والأجمل من وجهة نظري الشخصية أنها تجعلني أتساءل : كيف نجحت الصين في أن تنتقل من الفقر والبؤس والجوع إلى الصين التي نعرفها اليوم بقوتها وثرائها وانفتاحها.
BOOK
The miR-9b microRNA mediates dimorphism and development of wing in aphids
Wing dimorphism is a phenomenon of phenotypic plasticity in aphid dispersal. However, the signal transduction for perceiving environmental cues (e.g., crowding) and the regulation mechanism remain elusive. Here, we found that aci-miR-9b was the only down-regulated microRNA (miRNA) in both crowding-induced wing dimorphism and during wing development in the brown citrus aphid Aphis citricidus. We determined a targeted regulatory relationship between aci-miR-9b and an ABC transporter (AcABCG4). Inhibition of aci-miR-9b increased the proportion of winged offspring under normal conditions. Overexpression of aci-miR-9b resulted in decline of the proportion of winged offspring under crowding conditions. In addition, overexpression of aci-miR-9b also resulted in malformed wings during wing development. This role of aci-miR-9b mediating wing dimorphism and development was also confirmed in the pea aphid Acyrthosiphon pisum. The downstream action of aci-miR-9b-AcABCG4 was based on the interaction with the insulin and insulin-like signaling pathway. A model for aphid wing dimorphism and development was demonstrated as the following: maternal aphids experience crowding, which results in the decrease of aci-miR-9b. This is followed by the increase of ABCG4, which then activates the insulin and insulin-like signaling pathway, thereby causing a high proportion of winged offspring. Later, the same cascade, “miR-9b-ABCG4-insulin signaling,” is again involved in wing development. Taken together, our results reveal that a signal transduction cascade mediates both wing dimorphism and development in aphids via miRNA. These findings would be useful in developing potential strategies for blocking the aphid dispersal and reducing viral transmission.
Journal Article
Polysaccharides From Chrysanthemum morifolium Ramat Ameliorate Colitis Rats via Regulation of the Metabolic Profiling and NF-κ B/TLR4 and IL-6/JAK2/STAT3 Signaling Pathways
Studies have indicated that Chrysanthemum polysaccharides (CP) could prominently ameliorate colitis rats, but its possible mechanism remains unclear. In this study, the underlying mechanism of CP was explored by the metabolic profiling analysis and correlated signaling pathways. TNBS/ethanol induced colitis was used to investigate the intervention efficacy following oral administration of CP. The levels of cytokines such as TNF-α, IL-6, IFN-γ and IL-1β, and the activities of SOD, MPO, and MDA were determined. We also performed western-blot for p65, TLR4, p-JAK2, and STAT3 protein expression in the colon tissue to probe their mechanisms of correlated signaling pathways. What's more, the metabolic changes in plasma and urine from colitis rats were investigated based on UPLC-Q-TOF/MS combined with Metabolynx
software. The potential biomarkers and metabolic pathways were also tentatively confirmed. The metabolic profiles of plasma and urine were clearly improved in model rats after oral administration of CP. Thirty-two (17 in serum and 15 in urine) potential biomarkers were identified. The endogenous metabolites were mainly involved in linoleic acid, retinol, arachidonic acid, glycerophospholipid and primary bile acid metabolism in plasma, and nicotinate and nicotinamide, ascorbate and aldarate, histidine and β-alanine metabolism in urine. After polysaccharides intervention, these markers turned back to normal level at some extent. Meanwhile, the elevated expression levels of pp65, TLR4, p-STAT3, and p-JAK2 were significantly decreased after treatment. Results suggested that CP would be a potential prebiotics for alleviation of TNBS-induced colitis. The study paved the way for the further exploration of the pathogenesis, early diagnosis and curative drug development of the colitis.
Journal Article
Establishing mouse and human oral esophageal organoids to investigate the tumor immune response
Organoid culture systems are very powerful models that recapitulate in vivo organ development and disease pathogenesis, offering great promise in basic research, drug screening and precision medicine. However, the application of organoids derived from patients with cancer to immunotherapeutic research is a relatively untapped area. Esophageal cancer is one of the most lethal malignancies worldwide, including two major pathological subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma. ESCC shares many biological and genomic features with oral squamous cell cancers. Herein, we provide a versatile protocol for the establishment and maintenance of oral and esophageal organoid cultures derived from both murine and human samples. We describe culture conditions for organoids derived from normal tongue, esophagus and gastroesophageal junction, esophageal cancer and Barrett's esophagus. In addition, we establish an ex vivo model by co-culturing patient tumor-derived organoids and autologous CD8+ T lymphocytes to assess CD8+ T cell-mediated tumor killing. Our protocol can also be modified for organoid establishment from other squamous epithelia and carcinomas. The co-culture model can serve as a template for studies of other tumor-immune cell interactions and the efficacy of immune checkpoint blockade therapy.
Journal Article
Reciprocal inhibition between TP63 and STAT1 regulates anti-tumor immune response through interferon-γ signaling in squamous cancer
Squamous cell carcinomas (SCCs) are common and aggressive malignancies. Immune check point blockade (ICB) therapy using PD-1/PD-L1 antibodies has been approved in several types of advanced SCCs. However, low response rate and treatment resistance are common. Improving the efficacy of ICB therapy requires better understanding of the mechanism of immune evasion. Here, we identify that the SCC-master transcription factor TP63 suppresses interferon-γ (IFNγ) signaling. TP63 inhibition leads to increased CD8
+
T cell infiltration and heighten tumor killing in in vivo syngeneic mouse model and ex vivo co-culture system, respectively. Moreover, expression of TP63 is negatively correlated with CD8
+
T cell infiltration and activation in patients with SCC. Silencing of TP63 enhances the anti-tumor efficacy of PD-1 blockade by promoting CD8
+
T cell infiltration and functionality. Mechanistically, TP63 and STAT1 mutually suppress each other to regulate the IFNγ signaling by co-occupying and co-regulating their own promoters and enhancers. Together, our findings elucidate a tumor-extrinsic function of TP63 in promoting immune evasion of SCC cells. Over-expression of TP63 may serve as a biomarker predicting the outcome of SCC patients treated with ICB therapy, and targeting TP63/STAT/IFNγ axis may enhance the efficacy of ICB therapy for this deadly cancer.
TP63 is a master regulator transcription factor in squamous cell carcinomas (SCCs). Here the authors report that TP63 suppresses IFNγ signaling in SCC tumors and that its inhibition is associated with enhanced anti-tumor immunity and response to anti-PD1.
Journal Article
Virulence plasmid with IroBCDN deletion promoted cross-regional transmission of ST11-KL64 carbapenem-resistant hypervirulent Klebsiella pneumoniae in central China
Background
Carbapenem-resistant and hypervirulent
Klebsiella pneumoniae
(CR-hvKP) caused infections of high mortality and brought a serious impact on public health. This study aims to evaluate the epidemiology, resistance and virulence characteristics of CR-hvKP and to identify potential drivers of cross-regional transmission in different regions of China, in order to provide a basis for developing targeted prevention measures.
Methods
Clinical
K. pneumoniae
strains were collected from Jiujiang and Nanchang in Jiangxi province between November 2021 to June 2022. Clinical data of patients (age, sex, source of infection, and diagnosis) were also gathered. We characterized these strains for their genetic relatedness using PFGE, antimicrobial and virulence plasmid structures using whole-genome sequencing, and toxicity using
Galleria mellonella
infection model.
Results
Among 609 strains, 45 (7.4%) CR-hvKP were identified, while the strains.
isolated from Nanchang and Jiujiang accounted for 10.05% (36/358) and 3.59% (9/251). We observed that ST11-KL64 CR-hvKP had an overwhelming epidemic dominance in these two regions. Significant genetic diversity was identified among all ST11-KL64 CR-hvKP cross-regional transmission between Nanchang and Jiujiang and this diversity served as the primary driver of the dissemination of clonal groups. Virulence genes profile revealed that ST11-KL64 CR-hvKP might harbour incomplete pLVPK-like plasmids and primarily evolved from CRKP by acquiring the hypervirulence plasmid. We found the predominance of truncated-IncFIB/IncHI1B type virulence plasmids with a 25 kb fragment deletion that encoded
iroBCDN
clusters.
Conclusion
ST11-KL64 is the most cross-regional prevalent type CR-hvKPs in Jiangxi province, which mainly evolved from CRKPs by acquiring a truncated-IncHI1B/IncFIB virulence plasmid with the deletion of
iroBCDN
. Stricter surveillance and control measures are urgently needed to prevent the epidemic transmission of ST11-KL64 CR-hvKP.
Journal Article
The expansion and loss of specific olfactory genes in relatives of parasitic lice, the stored-product psocids (Psocodea: Liposcelididae)
Background
Booklice, belonging to the genus
Liposcelis
(Psocodea: Liposcelididae), commonly known as psocids, infest a wide range of stored products and are implicated in the transmission of harmful microorganisms such as fungi and bacteria. The olfactory system is critical for insect feeding and reproduction. Elucidating the molecular mechanisms of the olfactory system in booklice is crucial for developing effective control strategies. In this study, we aim to bridge this knowledge gap by leveraging the transcriptome and genome data from five
Liposcelis
species.
Result
Using HMMER method and manual annotation, we have identified common gene families associated with olfactory processes, including odorant binding proteins (OBPs), chemosensory proteins (CSPs), odorant receptors (ORs), ionotropic receptors (IRs), and sensory neuron membrane proteins (SNMPs). Specifically, we identified 94, 118, 26, 47, and 34 olfactory-related genes in
L. bostrychophila
,
L. tricolor
,
L. entomophila
,
L. decolor
, and
L. yangi
, respectively. Comparison of quantities revealed that the number of ORs and IRs in the genome is significantly higher than those identified in the transcriptome. This discrepancy may be due to the specific expression of these genes in certain tissues or their lack of expression during the experimental stage. Simultaneously, analysis of gene expression profiles across different developmental stages revealed varying periods of peak expression for olfactory-related genes. These results suggest that the identification of olfactory-related genes in booklice on a genome-wide scale is more feasible and reliable than using a transcriptome-based approach. Additionally, compared to parasitic lice, booklice possess significantly more olfactory-related genes. This increase may be due to the inability of parasitic lice to survive without a host, whereas booklice have a wide range of feeding habits and live in complex and variable environments. Furthermore, we observed that the IR gene family in
L. tricolor
has undergone a certain degree of amplification, which may facilitate its adaptation to diverse environmental conditions.
Conclusions
We identified olfactory-related genes of five
Liposcelis
species for the first time, providing valuable insights for future functional investigations into olfactory genes associated with pheromone and odorant recognition. These discoveries present promising targets for effectively managing psocid pests.
Journal Article
Non-Hermitian topological Anderson insulators
Non-Hermitian systems can exhibit exotic topological and localization properties. Here we elucidate the non-Hermitian effects on disordered topological systems using a nonreciprocal disordered Su-Schrieffer-Heeger model. We show that the non-Hermiticity can enhance the topological phase against disorders by increasing bulk gaps. Moreover, we uncover a topological phase which emerges under both moderate non-Hermiticity and disorders, and is characterized by localized insulating bulk states with a disorder-averaged winding number and zero-energy edge modes. Such topological phases induced by the combination of non-Hermiticity and disorders are dubbed
non-Hermitian topological Anderson insulators
. We reveal that the system has unique non-monotonous localization behavior and the topological transition is accompanied by an Anderson transition. These properties are general in other non-Hermitian models.
Journal Article
Experimental demonstration of a three-dimensional lithium niobate nonlinear photonic crystal
A nonlinear photonic crystal (NPC)1 possesses space-dependent second-order nonlinear coefficients, which can effectively control nonlinear optical interactions through quasi-phase matching2. Lithium niobate (LiNbO3) crystal is one of the most popular materials from which to fabricate NPC structures because of its excellent nonlinear optical properties3–5. One- and two-dimensional LiNbO3 NPCs have been widely utilized in laser frequency conversion6,7, spatial light modulation8–12 and nonlinear optical imaging13,14. However, limited by traditional poling methods, the experimental realization of three-dimensional (3D) NPCs remains one of the greatest challenges in the field of nonlinear optics1,15. Here, we present an experimental demonstration of a 3D LiNbO3 NPC by using a femtosecond laser to selectively erase the nonlinear coefficients in a LiNbO3 crystal16,17. The effective conversion efficiency is comparable to that of typical quasi-phase-matching processes. Such a 3D LiNbO3 NPC provides a promising platform for future nonlinear optical studies based on its unique ability to control nonlinear interacting waves in 3D configuration.By selectively erasing the nonlinear coefficients in a lithium niobate crystal using a femtosecond laser, a 3D nonlinear photonic crystal, with an effective conversion efficiency comparable to that of the typical quasi-phase-matching processes, is demonstrated.
Journal Article
Augmented expression of Ki-67 is correlated with clinicopathological characteristics and prognosis for lung cancer patients: an up-dated systematic review and meta-analysis with 108 studies and 14,732 patients
Background
Lung cancer ranks as the leading cause of cancer-related deaths worldwide and we performed this meta-analysis to investigate eligible studies and determine the prognostic effect of Ki-67.
Methods
In total, 108 studies in 95 articles with 14,732 patients were found to be eligible, of which 96 studies reported on overall survival (OS) and 19 studies reported on disease-free survival (DFS) with relation to Ki-67 expression in lung cancer patients.
Results
The pooled hazard ratio (HR) indicated that a high Ki-67 level could be a valuable prognostic factor for lung cancer (HR = 1.122 for OS,
P
< 0.001 and HR = 1.894 for DFS, P < 0.001). Subsequently, the results revealed that a high Ki-67 level was significantly associated with clinical parameters of lung cancer including age (odd ratio, OR = 1.246 for older patients,
P
= 0.018), gender (OR = 1.874 for males,
P
< 0.001) and smoking status (OR = 3.087 for smokers, P < 0.001). Additionally, significant positive correlations were found between Ki-67 overexpression and poorer differentiation (OR = 1.993,
P
= 0.003), larger tumor size (OR = 1.436, P = 0.003), and higher pathologic stages (OR = 1.867 for III-IV,
P
< 0.001). Furthermore, high expression of Ki-67 was found to be a valuable predictive factor for lymph node metastasis positive (OR = 1.653, P < 0.001) and advanced TNM stages (OR = 1.497 for stage III-IV,
P
= 0.024). Finally, no publication bias was detected in any of the analyses.
Conclusions
This study highlights that the high expression of Ki-67 is clinically relevant in terms of the prognostic and clinicopathological characteristics for lung cancer. Nevertheless, more prospective well-designed studies are warranted to validate these findings.
Journal Article