KRAS Dimerization Impacts MEK Inhibitor Sensitivity and Oncogenic Activity of Mutant KRAS.

The mechanism by which the wild-type KRAS allele imparts a growth inhibitory effect to oncogenic KRAS in various cancers, including lung adenocarcinoma (LUAD), is poorly understood. Here, using a genetically inducible model of KRAS loss of heterozygosity (LOH), we show that KRAS dimerization mediates wild-type KRAS-dependent fitness of human and murine KRAS mutant LUAD tumor cells and underlies resistance to MEK inhibition. These effects are abrogated when wild-type KRAS is replaced by KRASD154Q, a mutant that disrupts dimerization at the α4-α5 KRAS dimer interface without changing other fundamental biochemical properties of KRAS, both in vitro and in vivo. Moreover, dimerization has a critical role in the oncogenic activity of mutant KRAS. Our studies provide mechanistic and biological insights into the role of KRAS dimerization and highlight a role for disruption of dimerization as a therapeutic strategy for KRAS mutant cancers.

Cross-kingdom RNA interference mediated by insect salivary microRNAs may suppress plant immunity.

Communication between insects and plants relies on the exchange of bioactive molecules that traverse the species interface. Although proteinic effectors have been extensively studied, our knowledge of other molecules involved in this process remains limited. In this study, we investigate the role of salivary microRNAs (miRNAs) from the rice planthopper Nilaparvata lugens in suppressing plant immunity. A total of three miRNAs were confirmed to be secreted into host plants during insect feeding. Notably, the sequence-conserved miR-7-5P is specifically expressed in the salivary glands of N. lugens and is secreted into saliva, distinguishing it significantly from homologues found in other insects. Silencing miR-7-5P negatively affects N. lugens feeding on rice plants, but not on artificial diets. The impaired feeding performance of miR-7-5P-silenced insects can be rescued by transgenic plants overexpressing miR-7-5P. Through target prediction and experimental testing, we demonstrate that miR-7-5P targets multiple plant genes, including the immune-associated bZIP transcription factor 43 (OsbZIP43). Infestation of rice plants by miR-7-5P-silenced insects leads to the increased expression of OsbZIP43, while the presence of miR-7-5P counteracts this upregulation effect. Furthermore, overexpressing OsbZIP43 confers plant resistance against insects which can be subverted by miR-7-5P. Our findings suggest a mechanism by which herbivorous insects have evolved salivary miRNAs to suppress plant immunity, expanding our understanding of cross-kingdom RNA interference between interacting organisms.

Temporal regulation of MDA5 inactivation by Caspase-3 dependent cleavage of 14-3-3η.

The kinetics of type I interferon (IFN) induction versus the virus replication compete, and the result of the competition determines the outcome of the infection. Chaperone proteins that involved in promoting the activation kinetics of PRRs rapidly trigger antiviral innate immunity. We have previously shown that prior to the interaction with MAVS to induce type I IFN, 14-3-3η facilitates the oligomerization and intracellular redistribution of activated MDA5. Here we report that the cleavage of 14-3-3η upon MDA5 activation, and we identified Caspase-3 activated by MDA5-dependent signaling was essential to produce sub-14-3-3η lacking the C-terminal helix (αI) and tail. The cleaved form of 14-3-3η (sub-14-3-3η) could strongly interact with MDA5 but could not support MDA5-dependent type I IFN induction, indicating the opposite functions between the full-length 14-3-3η and sub-14-3-3η. During human coronavirus or enterovirus infections, the accumulation of sub-14-3-3η was observed along with the activation of Caspase-3, suggesting that RNA viruses may antagonize 14-3-3η by promoting the formation of sub-14-3-3η to impair antiviral innate immunity. In conclusion, sub-14-3-3η, which could not promote MDA5 activation, may serve as a negative feedback to return to homeostasis to prevent excessive type I IFN production and unnecessary inflammation.

A full-length glycoprotein mRNA vaccine confers complete protection against severe fever with thrombocytopenia syndrome virus, with broad-spectrum protective effects against bandaviruses.

Highly pathogenic viruses from family Phenuiviridae, which are mainly transmitted by arthropods, have intermittently sparked epidemics worldwide. In particular, tick-borne bandaviruses, such as severe fever with thrombocytopenia syndrome virus (SFTSV), continue to spread in mountainous areas, resulting in an average mortality rate as high as 10.5%, highlighting the urgency and importance of vaccine development. Here, an mRNA vaccine developed based on the full-length SFTSV glycoprotein, containing both the receptor-binding domain and the fusion domain, was shown to confer complete protection against SFTSV at a very low dose by triggering a type 1 helper T cell-biased cellular immune response in rodents. Moreover, the vaccine candidate elicited long-term immunity and protection against SFTSV for at least 5 months. Notably, it provided complete cross-protection against other bandaviruses, such as the Heartland virus and Guertu virus, in lethal challenge models. Further research revealed that the conserved epitopes among bandaviruses within the full-length SFTSV glycoprotein may facilitate broad-spectrum protection mediated by the cellular immune response. Collectively, these findings demonstrate that the full-length SFTSV glycoprotein mRNA vaccine is a promising vaccine candidate for SFTSV and other bandaviruses, and provide guidance for the development of broad-spectrum vaccines from conserved antigens and epitopes. IMPORTANCE: Tick-borne bandaviruses, such as SFTSV and Heartland virus, sporadically trigger outbreaks in addition to influenza viruses and coronaviruses, yet there are no specific vaccines or therapeutics against them. mRNA vaccine technology has advantages in terms of enabling in situ expression and triggering cellular immunity, thus offering new solutions for vaccine development against intractable viruses, such as bandaviruses. In this study, we developed a novel vaccine candidate for SFTSV by employing mRNA vaccination technology and using a full-length glycoprotein as an antigen target. This candidate vaccine confers complete and durable protection against SFTSV at a notably low dose while also providing cross-protection against Heartland virus and Guertu virus. This study highlights the prospective value of full-length SFTSV-glycoprotein-based mRNA vaccines and suggests a potential strategy for broad-spectrum bandavirus vaccines.

The JAK-STAT pathway promotes persistent viral infection by activating apoptosis in insect vectors.

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is an evolutionarily conserved signaling pathway that can regulate various biological processes. However, the role of JAK-STAT pathway in the persistent viral infection in insect vectors has rarely been investigated. Here, using a system that comprised two different plant viruses, Rice stripe virus (RSV) and Rice black-streaked dwarf virus (RBSDV), as well as their insect vector small brown planthopper, we elucidated the regulatory mechanism of JAK-STAT pathway in persistent viral infection. Both RSV and RBSDV infection activated the JAK-STAT pathway and promoted the accumulation of suppressor of cytokine signaling 5 (SOCS5), an E3 ubiquitin ligase regulated by the transcription factor STAT5B. Interestingly, the virus-induced SOCS5 directly interacted with the anti-apoptotic B-cell lymphoma-2 (BCL2) to accelerate the BCL2 degradation through the 26S proteasome pathway. As a result, the activation of apoptosis facilitated persistent viral infection in their vector. Furthermore, STAT5B activation promoted virus amplification, whereas STAT5B suppression inhibited apoptosis and reduced virus accumulation. In summary, our results reveal that virus-induced JAK-STAT pathway regulates apoptosis to promote viral infection, and uncover a new regulatory mechanism of the JAK-STAT pathway in the persistent plant virus transmission by arthropod vectors.

A 'rich-get-richer' mechanism drives patchy dynamics and resistance evolution in antibiotic-treated bacteria.

Bacteria in nature often form surface-attached communities that initially comprise distinct subpopulations, or patches. For pathogens, these patches can form at infection sites, persist during antibiotic treatment, and develop into mature biofilms. Evidence suggests that patches can emerge due to heterogeneity in the growth environment and bacterial seeding, as well as cell-cell signaling. However, it is unclear how these factors contribute to patch formation and how patch formation might affect bacterial survival and evolution. Here, we demonstrate that a 'rich-get-richer' mechanism drives patch formation in bacteria exhibiting collective survival (CS) during antibiotic treatment. Modeling predicts that the seeding heterogeneity of these bacteria is amplified by local CS and global resource competition, leading to patch formation. Increasing the dose of a non-eradicating antibiotic treatment increases the degree of patchiness. Experimentally, we first demonstrated the mechanism using engineered Escherichia coli and then demonstrated its applicability to a pathogen, Pseudomonas aeruginosa. We further showed that the formation of P. aeruginosa patches promoted the evolution of antibiotic resistance. Our work provides new insights into population dynamics and resistance evolution during surface-attached bacterial growth.

Data-driven learning of structure augments quantitative prediction of biological responses.

Multi-factor screenings are commonly used in diverse applications in medicine and bioengineering, including optimizing combination drug treatments and microbiome engineering. Despite the advances in high-throughput technologies, large-scale experiments typically remain prohibitively expensive. Here we introduce a machine learning platform, structure-augmented regression (SAR), that exploits the intrinsic structure of each biological system to learn a high-accuracy model with minimal data requirement. Under different environmental perturbations, each biological system exhibits a unique, structured phenotypic response. This structure can be learned based on limited data and once learned, can constrain subsequent quantitative predictions. We demonstrate that SAR requires significantly fewer data comparing to other existing machine-learning methods to achieve a high prediction accuracy, first on simulated data, then on experimental data of various systems and input dimensions. We then show how a learned structure can guide effective design of new experiments. Our approach has implications for predictive control of biological systems and an integration of machine learning prediction and experimental design.

Comparative transcriptomic analysis of salivary glands between the zoophytophagous Cyrtorhinus lividipennis and the phytozoophagous Apolygus lucorum.

BACKGROUND: Saliva plays a crucial role in shaping the feeding behavior of insects, involving processes such as food digestion and the regulation of interactions between insects and their hosts. Cyrtorhinus lividipennis serves as a predominant natural enemy of rice pests, while Apolygus lucorum, exhibiting phytozoophagous feeding behavior, is a destructive agricultural pest. In this study, a comparative transcriptome analysis, incorporating the published genomes of C.lividipennis and A.lucorum, was conducted to reveal the role of salivary secretion in host adaptation. RESULTS: In contrast to A.lucorum, C.lividipennis is a zoophytophagous insect. A de novo genome analysis of C.lividipennis yielded 19,706 unigenes, including 16,217 annotated ones. On the other hand, A.lucorum had altogether 20,111 annotated genes, as obtained from the published official gene set (20,353 unigenes). Functional analysis of the top 1,000 salivary gland (SG)-abundant genes in both insects revealed that the SG was a dynamically active tissue engaged in protein synthesis and secretion. Predictions of other tissues and signal peptides were compared. As a result, 94 and 157 salivary proteins were identified in C.lividipennis and A.lucorum, respectively, and were categorized into 68 and 81 orthogroups. Among them, 26 orthogroups were shared, potentially playing common roles in digestion and detoxification, including several venom serine proteases. Furthermore, 42 and 55 orthogroups were exclusive in C.lividipennis and A.lucorum, respectively, which were exemplified by a hyaluronidase in C.lividipennis that was associated with predation, while polygalacturonases in A.lucorum were involved in mesophyll-feeding patterns. CONCLUSIONS: Findings in this study provide a comprehensive insight into saliva secretions in C.lividipennis and A.lucorum via a transcriptome approach, reflecting the intricate connections between saliva secretions and feeding behaviors. It is found that conserved salivary secretions are involved in shaping the overlapping feeding patterns, while a plethora of unique salivary secretions may drive the evolution of specific feeding behaviors crucial for their survival. These results enhance our understanding of the feeding mechanisms in different insects from the perspective of saliva and contribute to future environmentally friendly pest control by utilizing predatory insects.

Revealing the spatiotemporal brain dynamics of covert speech compared with overt speech: A simultaneous EEG-fMRI study.

Covert speech (CS) refers to speaking internally to oneself without producing any sound or movement. CS is involved in multiple cognitive functions and disorders. Reconstructing CS content by brain-computer interface (BCI) is also an emerging technique. However, it is still controversial whether CS is a truncated neural process of overt speech (OS) or involves independent patterns. Here, we performed a word-speaking experiment with simultaneous EEG-fMRI. It involved 32 participants, who generated words both overtly and covertly. By integrating spatial constraints from fMRI into EEG source localization, we precisely estimated the spatiotemporal dynamics of neural activity. During CS, EEG source activity was localized in three regions: the left precentral gyrus, the left supplementary motor area, and the left putamen. Although OS involved more brain regions with stronger activations, CS was characterized by an earlier event-locked activation in the left putamen (peak at 262 ms versus 1170 ms). The left putamen was also identified as the only hub node within the functional connectivity (FC) networks of both OS and CS, while showing weaker FC strength towards speech-related regions in the dominant hemisphere during CS. Path analysis revealed significant multivariate associations, indicating an indirect association between the earlier activation in the left putamen and CS, which was mediated by reduced FC towards speech-related regions. These findings revealed the specific spatiotemporal dynamics of CS, offering insights into CS mechanisms that are potentially relevant for future treatment of self-regulation deficits, speech disorders, and development of BCI speech applications.

Horizontally Transferred Salivary Protein Promotes Insect Feeding by Suppressing Ferredoxin-Mediated Plant Defenses.

Herbivorous insects such as whiteflies, planthoppers, and aphids secrete abundant orphan proteins to facilitate feeding. Yet, how these genes are recruited and evolve to mediate plant-insect interaction remains unknown. In this study, we report a horizontal gene transfer (HGT) event from fungi to an ancestor of Aleyrodidae insects approximately 42 to 190 million years ago. BtFTSP1 is a salivary protein that is secreted into host plants during Bemisia tabaci feeding. It targets a defensive ferredoxin 1 in Nicotiana tabacum (NtFD1) and disrupts the NtFD1-NtFD1 interaction in plant cytosol, leading to the degradation of NtFD1 in a ubiquitin-dependent manner. Silencing BtFTSP1 has negative effects on B. tabaci feeding while overexpressing BtFTSP1 in N. tabacum benefits insects and rescues the adverse effect caused by NtFD1 overexpression. The association between BtFTSP1 and NtFD1 is newly evolved after HGT, with the homologous FTSP in its fungal donor failing to interact and destabilize NtFD1. Our study illustrates the important roles of horizontally transferred genes in plant-insect interactions and suggests the potential origin of orphan salivary genes.

Identification of tanshinone I as cap-dependent endonuclease inhibitor with broad-spectrum antiviral effect.

IMPORTANCE: The spread of avian-borne, tick-borne, and rodent-borne pathogens has the potential to pose a serious threat to human health, and candidate vaccines as well as therapeutics for these pathogens are urgently needed. Tanshinones, especially tanshinone I, were identified as a cap-dependent endonuclease inhibitor with broad-spectrum antiviral effects on negative-stranded, segmented RNA viruses including bandavirus, orthomyxovirus, and arenavirus from natural products, implying an important resource of candidate antivirals from the traditional Chinese medicines. This study supplies novel candidate antivirals for the negative-stranded, segmented RNA virus and highlights the endonuclease involved in the cap-snatching process as a reliable broad-spectrum antiviral target.

Protection of the receptor binding domain (RBD) dimer against SARS-CoV-2 and its variants.

IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants achieved immune escape and became less virulent and easily transmissible through rapid mutation in the spike protein, thus the efficacy of vaccines on the market or in development continues to be challenged. Updating the vaccine, exploring compromise vaccination strategies, and evaluating the efficacy of candidate vaccines for the emerging variants in a timely manner are important to combat complex and volatile SARS-CoV-2. This study reports that vaccines prepared from the dimeric receptor-binding domain (RBD) recombinant protein, which can be quickly produced using a mature and stable process platform, had both good immunogenicity and protection in vivo and could completely protect rodents from lethal challenge by SARS-CoV-2 and its variants, including the emerging Omicron XBB.1.16, highlighting the value of dimeric recombinant vaccines in the post-COVID-19 era.

Self-healing propagation of a longitudinally varying vector optical beam for distance measurement.

Based on the longitudinal manipulation of polarization, a special vector optical beam (VOB) with customized polarization variation in propagation direction can be generated, whose properties and applications remain to be studied. Here, the self-healing propagation behaviors of the longitudinally varying VOB after an opaque object are investigated, and the localized polarization responses on the object distance are revealed. On this basis, characteristic parameters are defined to measure the distance of object, achieving a minimum relative error of 0.63% in a longitudinal range of 300 mm. Besides, the correlations and uncoupling methods of object distance and size are discussed. Our studies open new ways to use the structural properties of VOB and may be instructive for laser measurement.

BNIP3L/NIX-mediated mitophagy alleviates passive stress-coping behaviors induced by tumor necrosis factor-α.

Recent studies based on animal models of various neurological disorders have indicated that mitophagy, a selective autophagy that eliminates damaged and superfluous mitochondria through autophagic degradation, may be involved in various neurological diseases. As an important mechanism of cellular stress response, much less is known about the role of mitophagy in stress-related mood disorders. Here, we found that tumor necrosis factor-α (TNF-α), an inflammation cytokine that plays a particular role in stress responses, impaired the mitophagy in the medial prefrontal cortex (mPFC) via triggering degradation of an outer mitochondrial membrane protein, NIP3-like protein X (NIX). The deficits in the NIX-mediated mitophagy by TNF-α led to the accumulation of damaged mitochondria, which triggered synaptic defects and behavioral abnormalities. Genetic ablation of NIX in the excitatory neurons of mPFC caused passive coping behaviors to stress, and overexpression of NIX in the mPFC improved TNF-α-induced synaptic and behavioral abnormalities. Notably, ketamine, a rapid on-set and long-lasting antidepressant, reversed the TNF-α-induced behavioral abnormalities through activation of NIX-mediated mitophagy. Furthermore, the downregulation of NIX level was also observed in the blood of major depressive disorder patients and the mPFC tissue of animal models. Infliximab, a clinically used TNF-α antagonist, alleviated both chronic stress- and inflammation-induced behavioral abnormalities via restoring NIX level. Taken together, these results suggest that NIX-mediated mitophagy links inflammation signaling to passive coping behaviors to stress, which underlies the pathophysiology of stress-related emotional disorders.

Gender differences in gastrointestinal, biopsychosocial and healthcare-seeking behaviors in Chinese patients with irritable bowel syndrome predominant with diarrhea.

BACKGROUND: Evidences of comparison of sex difference in Chinese irritable bowel syndrome (IBS) patients were few. We aim to compare gender difference in the biopsychosocial characteristics of Chinese patients of IBS predominant with diarrhea (IBS-D). METHODS: IBS-D patients meeting Rome III criteria were enrolled. We administered IBS symptom questionnaires, evaluation of psychological status (HAMD and HAMA scales) and IBS quality of life (IBS-QOL), dietary habits, healthcare seeking behaviors, and compared biopsychosocial characteristics between male and female patients. RESULTS: Four hundred and ninety patients were enrolled including 299 males and 191 females. More female patients reported abdominal pain associated with defecation (84.3% vs. 74.9%, P = 0.014) while males reported more abdominal discomfort (39.8% vs. 26.7%, P = 0.003). Females had higher IBS symptom score (9.7 ± 1.7 vs. 9.4 ± 1.4, P = 0.025) and more of females had severe abdominal pain/discomfort (17.8% vs. 12.4%, P = 0.013) while there were no significant differences of other bowel symptoms. Females reported higher incidence of comorbid anxiety state (64.9% vs. 52.8%, P = 0.008) and depression state (35.6% vs. 19.7%, P < 0.001) than males. Female patients also had lower IBS-QOL score (70.2 ± 20.4 vs. 75.1 ± 16.8, P = 0.028) and more frequent consultations, as well as less response for dietary modification than males. CONCLUSIONS: Chinese female patients with IBS-D had more prominent psychosocial disorders compared to male patients and their abdominal symptoms had minor differences.

Curcumin affects autophagy of prolactinoma cells by upregulating miR-206 to exert antitumor effects.

We explored the effects of curcumin on the aberrant biological behaviors of prolactinoma cells and the downstream pathways through which curcumin exerts its antitumor effects. We used quantitative reverse transcription-polymerase chain reaction assays to measure miR-206 expression levels in peripheral blood samples from patients with prolactinoma before and after curcumin treatment. We also investigated the proliferation level, viability, and invasion ability of groups of cells treated with different concentrations of curcumin using 3-(4,5)-dimethylthiahiazo (-z-y1)-3-di-phenytetrazoliumromide (MTT) assays, cell cloning assays, and Transwell assays, respectively. Furthermore, we determined the levels of autophagy-related proteins and protein kinase B/mammalian target of the rapamycin (Akt/mTOR) signaling pathway-related proteins in each group of treated cells by western blot. Curcumin treatment upregulated miR-206 expression levels in the peripheral blood of patients with prolactinoma and in GH3 cells. Knockdown of miR-206 expression enhanced the proliferation and invasive ability of GH3 cells, while curcumin treatment effectively inhibited the aberrant biological behavior of GH3 cells enhanced by miR-206 knockdown. miR-206 knockdown also activated the Akt/mTOR signaling pathway and inhibited autophagy in GH3 cells, and these changes were effectively reversed by curcumin treatment. Thus, curcumin inhibited the Akt/mTOR signaling pathway and promoted cell autophagy by miR-206 upregulation, resulting in antitumor effects that inhibited prolactinoma cell proliferation and invasion.

Developmental characteristics of aggregated lymphoid nodules area in the abomasum of fetal Bactrian camels (Camelus bactrianus).

BACKGROUND: Bactrian camel is one of the important economic animals in northwest China. They live in arid desert, and their gestation period is about 13 months, which is longer than other ruminants (such as cattle and sheep). The harsh living conditions have made its unique histological characteristics a research focus. Aggregated lymphoid nodules area (ALNA) in the abomasum of Bactrian camels, as one of the most important sites for the induction of the immune response, provide a comprehensive and effective protective role for the organism, and their lack of information will affect the feeding management, reproduction and epidemic prevention of Bactrian camels. In this study, the histological characteristics of the fetal ALNA in the abomasum of Bactrian camels at different developmental gestation have been described by using light microscopy and histology . RESULTS: The ALNA in the abomasum of the Chinese Alashan Bactrian camel is a special immune structure that was first discovered and reported by Wen-hui Wang. To further establish the developmental characteristics of this special structure in the embryonic stage, the abomasum ALNA of 8 fetuses of Alashan Bactrian camels with different gestational ages (5~13 months) were observed and studied by anatomy and histology. The results showed that the aggregation of reticular epithelial cells (RECs) surrounded by a very small number of lymphoid cells was detected for the first time in the abomasum of fetal camel at 5 months gestation, which was presumed to be primitive ALNA. At 7 months gestation, the reticular mucosal folds region (RMFR) appeared, but the longitudinal mucosal folds region (LMFR) was not significant, and histological observations showed that there were diffusely distributed lymphocytes around the RECs. At 10months gestation, RMFR and LMFR were clearly visible, lymphoid follicles appeared in histological observation, lymphocytes proliferated vigorously. By 13 months, the volume of lymphoid follicles increased, forming the subepithelial dome (SED), and there was a primitive interfollicular area between the lymphoid follicles, which contained high endothelial vein (HEV), but no germinal center (GC) was found. In summary, ALNA of Bactrian camels is not fully mature before birth. CONCLUSIONS: Generally, the small intestine PPs of ruminants (such as cattle and sheep) is already mature before birth, while the ALNA in the abomasum of Bactrian camels is not yet mature in the fetal period. During the development of ALNA in Bactrian camel, the development of lymphoid follicles extends from submucosa to Lamina propria. Interestingly, the deformation of FAE changes with age from simple columnar epithelium at the beginning of pregnancy to Simple cuboidal epithelium, which is opposite to the FAE deformation characteristics of PPs in the small intestine of fetal cattle and sheep. These results are the basis of further research on the specificity of ALNA in the abomasum of Bactrian camels.

Intrauterine fetal death due to rupture of umbilical vessels: a rare case of furcate cord insertion.

Furcate cord insertion refers to the separation of umbilical vessels before reaching the placenta, where the branching vessels normally attach at the edge of the placental parenchyma or near the placental membranes. This is an extremely rare abnormal umbilical cord insertion. This paper reported a case of a furcate cord insertion, where the rupture of exposed umbilical vessels led to intrauterine fetal death at full term. Through literature review, we analyzed the prenatal ultrasound characteristics and pregnancy outcomes of furcate cord insertions, with the aim to improve detection rates and reduce the risk of adverse pregnancy outcomes.

Tight focusing of the vector optical field with polarization varying along complex curves of the Poincaré sphere.

Different from the scalar optical field with spatially uniform polarization, the vector optical field exhibits inhomogeneous distribution of polarization on the cross section. Manipulating the variation of polarization in a single optical beam is important to acquire a flexible and controllable focused optical field. Previous studies mainly focused on the vector optical field with its polarization varying along a circular trajectory of the Poincaré sphere. Here, we demonstrate the tight focusing behaviors of the vector optical field with the polarization varying along complex curves of the Poincaré sphere, which is generated by the joint modulation of azimuthal phase and amplitude distributions of orthogonally polarized components. The longitudinal polarization component with a multipolar pattern in rotational symmetry can be achieved with similar distribution of the total focused field. The transverse and longitudinal spin angular momentum distributions in the focal space are discussed. Approximately pure transverse spin angular momentum can be constructed and manipulated in the focal space, which provides the possibility to manipulate the 3D spin flux for the applications of nano and spin photonics.

Selective autophagy of AKAP11 activates cAMP/PKA to fuel mitochondrial metabolism and tumor cell growth.

Autophagy is a catabolic pathway that provides self-nourishment and maintenance of cellular homeostasis. Autophagy is a fundamental cell protection pathway through metabolic recycling of various intracellular cargos and supplying the breakdown products. Here, we report an autophagy function in governing cell protection during cellular response to energy crisis through cell metabolic rewiring. We observe a role of selective type of autophagy in direct activation of cyclic AMP protein kinase A (PKA) and rejuvenation of mitochondrial function. Mechanistically, autophagy selectively degrades the inhibitory subunit RI of PKA holoenzyme through A-kinase-anchoring protein (AKAP) 11. AKAP11 acts as an autophagy receptor that recruits RI to autophagosomes via LC3. Glucose starvation induces AKAP11-dependent degradation of RI, resulting in PKA activation that potentiates PKA-cAMP response element-binding signaling, mitochondria respiration, and ATP production in accordance with mitochondrial elongation. AKAP11 deficiency inhibits PKA activation and impairs cell survival upon glucose starvation. Our results thus expand the view of autophagy cytoprotection mechanism by demonstrating selective autophagy in RI degradation and PKA activation that fuels the mitochondrial metabolism and confers cell resistance to glucose deprivation implicated in tumor growth.