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Transformable nanodrugs with changeable sizes and shapes allow for overcoming multiple biological barriers for enhanced drug delivery. This review aims to present an overview of the most recent development of smart nanodrugs in this emerging field.

Aqueous dispersed conjugated polymer dots (Pdots) have shown promising application in photocatalytic hydrogen evolution. To efficiently extract photogenerated charges from type-II heterojunction Pdots for hydrogen evolution, the mechanistic study of photophysical processes is essential for Pdot optimization. Within this work, we use a PFODTBT donor (D) polymer and an ITIC small molecule acceptor (A) as a donor/acceptor (D/A) model system to study their excited states and charge/energy transfer dynamics via steady-state and time-resolved photoluminescence spectroscopy, respectively. Charge-carrier generation and the recombination dynamics of binary Pdots with different D/A ratios were followed using femtosecond transient absorption spectroscopy. A significant spectral relaxation of photoluminescence was observed for individual D Pdots, implying an energetic disorder by nature. However, this was not seen for charge carriers in binary Pdots, probably due to the ultrafast charge generation process at an early time (

To investigate the occurrence of mosaicism in epilepsy probands and their parents using amplicon-based deep sequencing (ADS).Patients were recruited from the outpatient of Peking University First Hospital. Two hundred and sixty-four probands with pathogenic variants tested by next-generation sequencing (NGS) were enrolled.Mosaic variants were detected in seventeen disease-associated genes from 20 probands, 5 paternal, and 6 maternal parents. The frequency of mosaicism was 11.74% (31/264). Mosaicism in 11 genes was identified from 20 probands with the mutant allelic fractions (MAFs) of 12.95-38.00% in autosomal dominant genes. Five paternal mosaicisms were identified in genes with a MAF of 6.30-20.99%, and six maternal mosaic individuals with a MAF of 2.07-21.90%. Only four mosaic parents had milder seizure history. The affected sibling had the same phenotype consistent with that of the proband, who inherited the variant of SLC1A2 or STXBP1 from their unaffected mosaic mothers, respectively.Mosaic phenomenon is not rare in families with epilepsy. Phenotypes of mosaic parents were milder or normal. Mosaicism detection is helpful to identify the mutation origin and it provides a theoretical basis for prenatal diagnosis of family reproduction. ADS is a reliable way of mosaicism detection for clinical application.

Supplemental Figures S1-4. Supplementary Figure S1: eRapa prevents DMBA/TPA-induced dermal neoplasia and malignant degeneration in WT mice. Supplementary Figure S2: eRapa does not suppress mTORC1 signaling in whole skin. Supplementary Figure S3: eRapa is not a calorie restriction mimetic. Supplementary Figure S4: eRapa prevents DMBA/TPA-induced dermal neoplasia in T cell deficient mice.

The FDA-approved mTOR inhibitor rapamycin mediates important immune effects, but its contributions to the anticancer effects of the drug are unclear. Here we report evidence that rapamycin-mediated cancer protection relies upon stimulation of γδ T cells. In a well-established mouse model of carcinogen and inflammation-driven skin carcinogenesis, IFNγ recruited γδ TCRmid T cells to the epidermis where rapamycin boosted their perforin-dependent antitumor properties. These antitumor cells were mostly Vγ5−Vγ4−Vγ1− in phenotype. IFNγ signals were required in both hematopoietic and nonhematopoietic cells for rapamycin to optimally promote epidermal infiltration of γδ TCRmid T cells, as mediated by CXCR3–CXCL10 interactions, along with the antitumor effects of these cells. In mouse xenograft models of human squamous cell carcinoma, rapamycin improved human γδ T-cell–mediated cancer cell killing. Our results identify immune mechanisms for the cancer prevention and treatment properties of rapamycin, challenging the paradigm that mTOR inhibition acts primarily by direct action on tumor cells. Cancer Res; 76(20); 5970–82. ©2016 AACR.

S1 shows DMBA/TPA modulation of epidermal alphabeta and gammadelta TCRhi T cells in WT and CXCR3-/- mice. S2 shows epidermal chemokines in WT and IFN-gamma-/- mice treated with Eudragit control or eRapa. S3 shows mTOR signaling in epidermal and draining lymph node T cells. S4 shows human gammadelta TCR expression in gammadelta T cells.

Supplementary figure 1. Rapamycin reduces EL4 bone marrow infiltration. Supplementary figure 2. HD rapamycin impairs T cell activation and infiltration. Supplementary figure 3. Effects of rapamycin on mTOR signals and Ki67 (proliferation) in EL4 cells studied ex vivo. Supplementary figure 4. Dose response effects of rapamycin on EL4 in vivo. Supplementary figure 5. EL4 is refractory to many standard immunotherapies. Supplementary figure 6. LD rapamycin plus DD-mediated EL4 cell death is not blocked by anti-CD25 in vivo. Supplementary figure 7. LD rapamycin improves DD treatment efficacy of B16F10. Supplementary figure 8. Rapamycin + DD killing of EL4 and B16 cells is blocked with anti-CD25 + anti-CD22 in vitro. Supplementary figure 9. CD25 and CD122 expression are not upregulated by rapamycin treatment in vitro in mouse tumor lines B16F10 or ID8agg. Supplementary figure 10. CD25 and CD122 expression are not upregulated by rapamycin treatment in vivo in mouse challenged with B16F10. Supplementary figure 11. CD25 and CD122 expression on human NM001 and Jurkat cell lines is unchanged with temsirolimus in vitro.

mTOR drives tumor growth but also supports T-cell function, rendering the applications of mTOR inhibitors complex especially in T-cell malignancies. Here, we studied the effects of the mTOR inhibitor rapamycin in mouse EL4 T-cell lymphoma. Typical pharmacologic rapamycin (1–8 mg/kg) significantly reduced tumor burden via direct suppression of tumor cell proliferation and improved survival in EL4 challenge independent of antitumor immunity. Denileukin diftitox (DD)–mediated depletion of regulatory T cells significantly slowed EL4 growth in vivo in a T-cell–dependent fashion. However, typical rapamycin inhibited T-cell activation and tumor infiltration in vivo and failed to boost DD treatment effects. Low-dose (LD) rapamycin (75 μg/kg) increased potentially beneficial CD44hiCD62L+ CD8+ central memory T cells in EL4 challenge, but without clinical benefit. LD rapamycin significantly enhanced DD treatment efficacy, but DD plus LD rapamycin treatment effects were independent of antitumor immunity. Instead, rapamycin upregulated EL4 IL2 receptor in vitro and in vivo, facilitating direct DD tumor cell killing. LD rapamycin augmented DD efficacy against B16 melanoma and a human B-cell lymphoma, but not against human Jurkat T-cell lymphoma or ID8agg ovarian cancer cells. Treatment effects correlated with IL2R expression, but mechanisms in some tumors were not fully defined. Overall, our data define a distinct, biphasic mechanisms of action of mTOR inhibition at doses that are clinically exploitable, including in T-cell lymphomas. Cancer Res; 77(2); 520–31. ©2016 AACR.

Supplementary figures 1-10. Figure S1. IL-2c increases conventional CD4 T cell in ascites three weeks after final IL-2c, but does not affect ascites Treg and effector T cell numbers at one week after final IL-2c administration. Figure S2. IL-2c treatment increases CD8+ central and effector memory T cells in the ascites, and central memory T cells in TDLN. Fig S3. Additional Treg phenotype in ascites and TDLN after IL-2c treatment. Fig S4. IL-2c directly inhibits Treg suppression specifically in the tumor microenvironment. Fig S5. IL-2 signaling is not impaired in TDLN after IL-2c treatment. Figure S6. Specific Treg depletion is highly effective against ID8agg. Figure S7. αCD25 attenuates IL-2c-induced tumor rejection and T cell function in ID8agg OC. Figure S8. IL-2c promotes intratumoral T cell infiltration. Figure S9. IL-2c reduces intratumoral Treg activation and functional molecules in B16 melanoma. Figure S10. IL-2c increases TIGIT+LAG-3+PD-1+ CD8+ T cells in B16 tumors.

Supplementary Methods from CD73 on Tumor Cells Impairs Antitumor T-Cell Responses: A Novel Mechanism of Tumor-Induced Immune Suppression

Supplementary Figures 1-7 from CD73 on Tumor Cells Impairs Antitumor T-Cell Responses: A Novel Mechanism of Tumor-Induced Immune Suppression

A semiartificial photosynthesis approach that utilizes enzymes for solar fuel production relies on efficient photosensitizers that should match the enzyme activity and enable long-term stability. Polymer dots (Pdots) are biocompatible photosensitizers that are stable at pH 7 and have a readily modifiable surface morphology. Therefore, Pdots can be considered potential photosensitizers to drive such enzyme-based systems for solar fuel formation. This work introduces and unveils in detail the interaction within the biohybrid assembly composed of binary Pdots and the HydA1 [FeFe]-hydrogenase from Chlamydomonas reinhardtii. The direct attachment of hydrogenase on the surface of toroid-shaped Pdots was confirmed by agarose gel electrophoresis, cryogenic transmission electron microscopy (Cryo-TEM), and cryogenic electron tomography (Cryo-ET). Ultrafast transient spectroscopic techniques were used to characterize photoinduced excitation and dissociation into charges within Pdots. The study reveals that implementation of a donor-acceptor architecture for heterojunction Pdots leads to efficient subpicosecond charge separation and thus enhances hydrogen evolution (88 460 mu mol(H2).g(H2ase)(-1).h(-1)). Adsorption of [FeFe]-hydrogenase onto Pdots resulted in a stable biohybrid assembly, where hydrogen production persisted for days, reaching a TON of 37 500 +/- 1290 in the presence of a redox mediator. This work represents an example of a homogeneous biohybrid system combining polymer nanoparticles and an enzyme. Detailed spectroscopic studies provide a mechanistic understanding of light harvesting, charge separation, and transport studied, which is essential for building semiartificial photosynthetic systems with efficiencies beyond natural and artificial systems.

Three major pathogenic states of the prostate, including benign prostatic hyperplasia, prostate cancer, and prostatitis, are related to the local inflammation. However, the mechanisms underlying the initiation of prostate inflammation remain largely unknown. Given that the innate immune responses of the tissue-specific cells to microbial infection or autoantigens contribute to local inflammation, this study focused on pattern recognition receptor (PRR)-initiated innate immune responses in mouse prostatic epithelial cells (PECs). Primary mouse PECs abundantly expressed Toll-like receptor 3 (TLR3), TLR4, TLR5, melanoma differentiation-associated protein 5 (MDA5), and IFN-inducible protein 16 (p204 in mouse). These PRRs can be activated by their respective ligands: lipopolysaccharide (LPS) and flagellin of Gram-negative bacteria for TLR4 and TLR5, polyinosinicpolycytidylic acid (poly(I:C)) for TLR3 and MDA5, and herpes simplex virus DNA analog (HSV60) for p204. LPS and flagellin predominantly induced the expression of inflammatory cytokines, including tumor necrosis factor alpha (TNFA), interleukin 6 (IL6), chemokines monocyte chemoattractant protein-1 (MCP1), and C-X-C motif chemokine 10 (CXCL10). Poly(I:C) and HSV60 predominantly induced the expression of type 1 interferons (IFNA and IFNB) and antiviral proteins: Mx GTPase 1, 2′,5′-oligoadenylate synthetase 1, and IFN-stimulated gene 15. The replication of mumps virus in PECs was inhibited by type 1 IFN signaling. These findings provide insights into the mechanisms underlying innate immune response in the prostate.Summary sentenceToll-like receptors 4, 5 and nucleic acid sensors initiate innate immune responses in prostatic epithelial cells after challenge with their respective ligands, which may be associated with inflammation in the prostate.

Many immune responses depend upon activation of NF-κB, an important transcription factor in the elicitation of a cytokine response. Here we show that N4BP1 inhibits TLR-dependent activation of NF-κB by interacting with the NF-κB signaling essential modulator (NEMO, also known as IκB kinase γ) to attenuate NEMO–NEMO dimerization or oligomerization. The UBA-like (ubiquitin associated-like) and CUE-like (ubiquitin conjugation to ER degradation-like) domains in N4BP1 mediate interaction with the NEMO COZI domain. Both in vitro and in mice, N4bp1 deficiency specifically enhances TRIF-independent (TLR2, TLR7, or TLR9-mediated) but not TRIF-dependent (TLR3 or TLR4-mediated) NF-κB activation, leading to increased production of proinflammatory cytokines. In response to TLR4 or TLR3 activation, TRIF causes activation of caspase-8, which cleaves N4BP1 distal to residues D424 and D490 and abolishes its inhibitory effect. N4bp1−/− mice also have diminished numbers of T cells in the peripheral blood. Our work identifies N4BP1 as an inhibitory checkpoint protein that must be overcome to activate NF-κB, and a TRIF-initiated caspase-8-dependent mechanism by which this is accomplished., NF-κB signalling is critical to TLR mediated cytokine release in various immune responses. Here the authors show how N4BP1 inhibits NEMO signalling and subsequent NF-κB activation and how this pathway is negatively regulated by caspase-8 cleavage of N4BP1.

The IL2 receptor (IL2R) is an attractive cancer immunotherapy target that controls immunosuppressive T regulatory cells (Treg) and antitumor T cells. Here we used IL2Rβ-selective IL2/anti-IL2 complexes (IL2c) to stimulate effector T cells preferentially in the orthotopic mouse ID8agg ovarian cancer model. Despite strong tumor rejection, IL2c unexpectedly lowered the tumor microenvironmental CD8+/Treg ratio. IL2c reduced tumor microenvironmental Treg suppression and induced a fragile Treg phenotype, helping explain improved efficacy despite numerically increased Tregs without affecting Treg in draining lymph nodes. IL2c also reduced Treg-mediated, high-affinity IL2R signaling needed for optimal Treg functions, a likely mechanism for reduced Treg suppression. Effector T-cell IL2R signaling was simultaneously improved, suggesting that IL2c inhibits Treg functions without hindering effector T cells, a limitation of most Treg depletion agents. Anti-PD-L1 antibody did not treat ID8agg, but adding IL2c generated complete tumor regressions and protective immune memory not achieved by either monotherapy. Similar anti-PD-L1 augmentation of IL2c and degradation of Treg functions were seen in subcutaneous B16 melanoma. Thus, IL2c is a multifunctional immunotherapy agent that stimulates immunity, reduces immunosuppression in a site-specific manner, and combines with other immunotherapies to treat distinct tumors in distinct anatomic compartments. Significance: These findings present CD122-targeted IL2 complexes as an advancement in cancer immunotherapy, as they reduce Treg immunosuppression, improve anticancer immunity, and boost PD-L1 immune checkpoint blockade efficacy in distinct tumors and anatomic locations.

Lead bromide perovskite solar cells (PSCs) have attracted increasing interest partly because of the high open-circuit voltage that has been obtained. Here, we present a simple way to prepare PSCs based on formamidinium lead tribromide, FAPbBr(3), by adding methylammonium chloride and methylammonium bromide into the precursor solution. With this method, high-quality and pin-hole free perovskite films with large crystal sizes were prepared. These additives result in a power conversion efficiency (PCE) of 7.9%, almost free of hysteresis, for a device on a rigid glass substrate. The first flexible lead bromide PSC is also prepared in this work and the flexible PSC exhibited a high PCE of 5.0%.

Production of renewable fuels from solar energy and abundant resourses, such as water and carbon dioxide, via photocatalytic reactions is seen as a promising strategy to adequately address the climate challenge. Photocatalytic systems based on organic polymer nanoparticles (PNPs) are seen as one avenue to transform solar energy into hydrogen and other solar fuels. Semiconducting PNPs are light-harvesting materials with exceptional optical properties, photostability, low cost and low cytotoxity, whose performance surpasses conventional organic dyes and inorganic semiconductors. This review introduces the optimization strategies for the preparation methods of PNP via cocatalyst loading and morphology tuning. We present an analysis on how the preparative methods will impact the physico-chemical properties of these materials, and thus the catalytic activity. A list of experimental techniques is presented for characterization of the physico-chemical properties (optical, morphological, electrochemical and catalytic properties) of PNPs. We provide detailed analysis of PNP photochemistry during photocatalysis with focus on the mechanistic understanding of processes of internal charge generation and transport to the catalyst. This tutorial review provides the reader with the guidelines on current strategies used to optimize PNP performance highlighting the future directions of polymer nano-photocatalysts development.

Background LAMA2-related muscular dystrophy including LAMA2-related congenital muscular dystrophy (LAMA2-CMD) and autosomal recessive limb-girdle muscular dystrophy-23 (LGMDR23) is caused by LAMA2 pathogenic variants. We aimed to describe the natural history and establish genotype–phenotype correlations in a large cohort of Chinese patients with LAMA2-related muscular dystrophy. Methods Clinical and genetic data of LAMA2-related muscular dystrophy patients enrolled from ten research centers between January 2003 and March 2021 were collected and analyzed. Results One hundred and thirty patients (116 LAMA2-CMD and 14 LGMDR23) were included. LAMA2-CMD group had earlier onset than LGMDR23 group. Head control, independent sitting and ambulation were achieved in 76.3%, 92.6% and 18.4% of LAMA2-CMD patients at median ages of 6.0 months (range 2.0–36.0 months), 11.0 months (range 6.0–36.0 months), and 27.0 months (range 18.0–84.0 months), respectively. All LGMDR23 patients achieved independent ambulation at median age of 18.0 months (range 13.0–20.0 months). Motor regression in LAMA2-CMD mainly occurred concurrently with rapid progression of contractures during 6–9 years old. Twenty-four LAMA2-related muscular dystrophy patients died, mostly due to severe pneumonia. Seizures occurred in 35.7% of LGMDR23 and 9.5% of LAMA2-CMD patients. Forty-six novel and 97 known LAMA2 disease-causing variants were identified. The top three high-frequency disease-causing variants in Han Chinese patients were c.7147C > T (p.R2383*), exon 4 deletion, and c.5156_5159del (p.K1719Rfs*5). In LAMA2-CMD, splicing variants tended to be associated with a relatively mild phenotype. Nonsense variants were more frequent in LAMA2-CMD (56.9%, 66/116) than in LGMDR23 (21.4%, 3/14), while missense disease-causing variants were more frequent in LGMDR23 (71.4%, 10/14) than in LAMA2-CMD (12.9%, 15/116). Copy number variations were identified in 26.4% of survivors and 50.0% of nonsurvivors, suggesting that copy number variations were associated with lower rate of survival (p = 0.029). Conclusions This study provides better understandings of natural history and genotype–phenotype correlations in LAMA2-related muscular dystrophy, and supports therapeutic targets for future researches.

Forward genetic studies use meiotic mapping to adduce evidence that a particular mutation, normally induced by a germline mutagen, is causative of a particular phenotype. Particularly in small pedigrees, cosegregation of multiple mutations, occasional unawareness of mutations, and paucity of homozygotes may lead to erroneous declarations of cause and effect. We sought to improve the identification of mutations causing immune phenotypes in mice by creating Candidate Explorer (CE), a machine-learning software program that integrates 67 features of genetic mapping data into a single numeric score, mathematically convertible to the probability of verification of any putative mutation–phenotype association. At this time, CE has evaluated putative mutation–phenotype associations arising from screening damaging mutations in ∼55% of mouse genes for effects on flow cytometry measurements of immune cells in the blood. CE has therefore identified more than half of genes within which mutations can be causative of flow cytometric phenovariation in Mus musculus. The majority of these genes were not previously known to support immune function or homeostasis. Mouse geneticists will find CE data informative in identifying causative mutations within quantitative trait loci, while clinical geneticists may use CE to help connect causative variants with rare heritable diseases of immunity, even in the absence of linkage information. CE displays integrated mutation, phenotype, and linkage data, and is freely available for query online.

Objective: To identify potential serum protein candidates involved in linking the traditional Chinese medicine (TCM)-defined qi deficiency constitution (QDC) to Pi-qi-deficiency syndrome (PQDS) of chronic superficial gastritis (CSG). Methods: Using participants with the TCM-defined balanced constitution as a control population, label-free quantitative proteomics was adopted to identify differentially expressed proteins (DEPs) in serum samples from two case populations: case population 1 (participants with QDC) and case population 2 (patients with PQDS of CSG). The DEPs discovered in both case populations were analyzed to identify common DEPs as potential candidates for proteins involved in the link between QDC and PQDS. Based on Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) and Gene Ontology (GO) enrichment analysis and analysis of protein–protein interaction networks, we evaluated the possible functions of these potential serum candidates. Results: We discovered 24 and 28 proteins that were differentially expressed in case populations 1 and 2, respectively, compared with the control population. Hierarchical clustering analysis showed that the expression profile of DEPs of individuals from the same population clustered well, while those from different populations were segregated. Furthermore, GO analysis revealed the 10 DEPs that were common to both case populations to be mainly associated with negative regulation of cellular metabolic and immune system processes while KEGG analysis indicated these proteins to be associated with complement and coagulation cascades and peroxisome proliferator-activated receptor signaling. Notably, serum levels of C4b-binding protein beta chain, glycosylphosphatidylinositol-specific phospholipase D1 and MS-F1 light chain variable region proteins were notably higher in the two case populations compared with the control, particularly in the case of CSG with PQDS. Conclusion: The results presented here provide new insights into the molecular mechanisms underlying development of PQDS of CSG from QDC, and suggest candidate serum biomarkers for future application in integrative medicine. Keywords: Qi deficiency constitution, Pi-qi-deficiency syndrome, Chronic superficial gastritis, Serum biomarker

We aimed to investigate whether the cardioprotection of sevoflurane against ischemia–reperfusion (IR) injury is via inhibiting endoplasmic reticulum stress. The rat in vivo model of myocardial IR injury was induced by ligation of the left anterior descending coronary artery. Sevoflurane significantly ameliorated the reduced cardiac function, increased infarct size, and elevated troponin I level and lactate dehydrogenase activity in plasma induced by IR injury. Sevoflurane suppressed the IR-induced myocardial apoptosis. The increased protein levels of glucose-regulated protein 78 and C/EBP homologous protein (CHOP) after myocardial IR were significantly reduced by sevoflurane. The protein levels of phosphorylated protein kinase RNA-like endoplasmic reticulum kinase (PERK), phosphorylated eukaryotic initiation factor 2 (eIF2α), and activating transcription factor 4 (ATF4) were significantly increased in rats with IR and attenuated by sevoflurane treatment. The phosphorylation of Akt was further activated by sevoflurane. The cardioprotection of sevoflurane could be blocked by wortmannin, a PI3K/Akt inhibitor. Our results suggest that the cardioprotection of sevoflurane against IR injury might be mediated by suppressing PERK/eIF2a/ATF4/CHOP signaling via activating the Akt pathway, which helps in understanding the novel mechanism of the cardioprotection of sevoflurane.

LAMA2-related muscular dystrophy (LAMA2-MD) is classified into congenital muscular dystrophy type 1A (MDC1A) and autosomal recessive limb-girdle muscular dystrophy-23 (LGMDR23). The purpose of this study was to identify the involvement pattern of thigh muscles of LAMA2-MD patients on magnetic resonance imaging. Fourteen MDC1A and 3 LGMDR23 patients were included, with 21 known and 8 novel LAMA2 disease-causing variants. In LAMA2-MD, the gluteus maximus, anterior (quadriceps femoris) and posterior (adductor magnus and biceps femoris) thigh muscles were extensively and severely affected with fatty infiltration, with relatively sparing of the adductor longus. The pattern of muscle involvement was similar between MDC1A and LGMDR23, but more severe in MDC1A, as well as in LAMA2-MD patients without ambulation. The rather peculiar pattern of the adductor magnus and long head of the biceps femoris first and severely affected in the mid-thigh level was found in LGMDR23. Strong correlation between fatty infiltration and age as well as disease duration was observed for the adductor longus in MDC1A. Edema and atrophy selectively involved in some muscles. The pattern of fatty infiltration on thigh muscle MRI of LAMA2-MD could provide important information for the diagnosis, differential diagnosis and assessment of clinical severity.

Numerous types of viruses have been found in human semen, which raises concerns about the sexual transmission of these viruses. The overall effect of semen on viral infection and transmission have yet to be fully investigated. In the present study, we aimed at the effect of seminal plasma (SP) on viral infection by focusing on the mumps viral (MuV) infection of HeLa cells. MuV efficiently infected HeLa cells in vitro. MuV infection was strongly inhibited by the pre-treatment of viruses with SP. SP inhibited MuV infection through the impairment of the virus’s attachment to cells. The antiviral activity of SP was resistant to the treatment of SP with boiling water, Proteinase K, RNase A, and DNase I, suggesting that the antiviral factor would not be proteins and nucleic acids. PNGase or PLA2 treatments did not abrogate the antiviral effect of SP against MuV. Further, we showed that the prostatic fluid (PF) showed similar inhibition as SP, whereas the epididymal fluid and seminal vesicle extract did not inhibit MuV infection. Both SP and PF also inhibited MuV infection of other cell types, including another human cervical carcinoma cell line C33a, mouse primary epididymal epithelial cells, and Sertoli cell line 15P1. Moreover, this inhibitory effect was not specific to MuV, as the herpes simplex virus 1, dengue virus 2, and adenovirus 5 infections were also inhibited by SP and PF. Our findings suggest that SP contains a prostate-derived pan-antiviral factor that may limit the sexual transmission of various viruses.

Panchromatic ternary polymer dots (Pdots) consisting of two conjugated polymers (PFBT and PFODTBT) based on fluorene and benzothiadiazole groups, and one small molecular acceptor (ITIC) have been prepared and assessed for photocatalytic hydrogen production with the assistance of a Pt cocatalyst. Femtosecond transient absorption spectroscopic studies of the ternary Pdots have revealed both energy and charge transfer processes that occur on the time scale of sub-picosecond between the different components. They result in photogenerated electrons being located mainly at ITIC, which acts as both electron and energy acceptor. Results from cryo-transmission electron microscopy suggest that ITIC forms crystalline phases in the ternary Pdots, facilitating electron transfer from ITIC to the Pt cocatalyst and promoting the final photocatalytic reaction yield. Enhanced light absorption, efficient charge separation, and the ideal morphology of the ternary Pdots have rendered an external quantum efficiency up to 7% at 600 nm. Moreover, the system has shown a high stability over 120 h without obvious degradation of the photocatalysts.

Endoplasmic reticulum (ER) calcium (Ca(2+)) stores are critical to proteostasis, intracellular signaling, and cellular bioenergetics. Through forward genetic screening in mice, we identified two members of a new complex, Pacs1 and Wdr37, which are required for normal ER Ca(2+) handling in lymphocytes. Deletion of Pacs1 or Wdr37 caused peripheral lymphopenia that was linked to blunted Ca(2+) release from the ER after antigen receptor stimulation. Pacs1‐deficient cells showed diminished inositol triphosphate receptor expression together with increased ER and oxidative stress. Mature Pacs1 (−/−) B cells proliferated and died in vivo under lymphocyte replete conditions, indicating spontaneous loss of cellular quiescence. Disruption of Pacs1‐Wdr37 did not diminish adaptive immune responses, but potently suppressed lymphoproliferative disease models by forcing loss of quiescence. Thus, Pacs1‐Wdr37 plays a critical role in stabilizing lymphocyte populations through ER Ca(2+) handling and presents a new target for lymphoproliferative disease therapy.

Organic semiconducting polymers dots (Pdots) have recently shown efficient photocatalytic activity for hydrogen evolution in an aqueous phase. However, colloidal Pdots face problems of aggregation and precipitation during the photocatalytic reaction due to unavoidable collisions between particles, thus resulting in a short catalytic lifetime. In this work, in situ preparation of PFBT Pdots on the surface of microbeads is reported. Results indicate that, with this facile method and support of a template, the photocatalytic properties of PFBT Pdots can be highly enhanced.