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Mycoplasma pneumoniae is the most common pathogen causing respiratory tract infection, and the P1 protein on its adhesion organelle plays a crucial role during the pathogenic process. A variety of experiments, including enzyme-linked immunosorbent assay (ELISA), coimmunoprecipitation, adhesion, and adhesion inhibition assay, have demonstrated that the M. pneumoniae P1 protein can interact with vimentin, that the adhesion of M. pneumoniae and recombinant P1 protein to BEAS-2B cells was affected by the expression level of vimentin.

By interacting with the receptor on the host cells membrane, Mycoplasma genitalium, a prokaryotic bacterium primarily transmitted through sexual contact, can adhere to and even enter cells. The adhesion protein of M. genitalium (MgPa) plays a critical function in the adhering and subsequent invasion into host cells. Our prior studies verified that cyclophilin A (CypA) was the receptor of MgPa on human urethral epithelial cells (SV-HUC-1) membrane and could induce pro-inflammatory cytokines production through the CypA-CD147-ERK-NF-κB pathway. This research aims to understand how MgPa interacts with its membrane receptor CypA to cause apoptosis in host cells. We employed flow cytometry to see if MgPa prevents or enhances apoptosis of SV-HUC-1 cells. The apoptosis-related proteins such as Bax, caspase-3, and cleaved caspase-3 were assayed using Western blot. Results suggested that MgPa could inhibit the apoptosis of SV-HUC-1 cells. And we demonstrated that interference with the expression of CypA or CD147 significantly reversed the inhibitory effect of MgPa on SV-HUC-1 cells apoptosis, indicating that MgPa inhibited urothelial cells apoptosis through CypA/CD147. Furthermore, we discovered that MgPa regulates the PI3K/Akt/NF-κB pathway through CypA/CD147 to inhibit SV-HUC-1 cells apoptosis. Ultimately, the inhibitory effect of MgPa on the apoptosis of the urothelial epithelial cells extracted from CypA-knockout mice was validated by Annexin V/PI assay. The results corroborated that MgPa could also inhibit mouse urothelial epithelial cells apoptosis. In summary, we demonstrated that MgPa could inhibit SV-HUC-1 cells apoptosis via regulating the PI3K/Akt/NF-κB pathway through CypA/CD147, providing experimental evidence for elucidating the survival strategies of M. genitalium in host cells. KEY POINTS: • M. genitalium protein of adhesion inhibited human urethral epithelial cells apoptosis through CypA-CD147 activating the signal pathway of PI3K/Akt/NF-κB • The knockdown of CypA and CD147 could downregulate the M. genitalium -activated PI3K/Akt/NF-κB pathway in SV-HUC-1 cells • MgPa could inhibit the apoptosis of normal C57BL mouse primary urethral epithelial cells, but not for CypA-knockout C57BL mouse primary urethral epithelial cells.

Cyclophilin A (CypA), a key member of the immunophilin family, is the most abundantly expressed isozyme of the 18 known human cyclophilins. Besides acting as an intracellular receptor for cyclosporine A, CypA plays a vital role in microorganismal infections, cardiovascular diseases, liver diseases, kidney diseases, neurodegeneration, cancer, rheumatoid arthritis, periodontitis, sepsis, asthma, and aging. This review focuses on the pivotal roles of CypA in the infection of etiological agents, which manifests mainly in promoting or inhibiting viral replication based on the host cell type and viral species. CypA can interact with viral proteins and thus regulate the replication cycle of the virus. CypA is involved in pathogenic bacterial infections by regulating the formation of host actin skeleton or membrane translocation of bacterial toxins, or mediated the adhesion of Mycoplasma genitalium during the infection processes by acting as a cellular receptor of M. genitalium. CypA also plays a critical role in infection or the life cycle of certain parasites or host immune regulation. Moreover, we summarized the current understanding of CypA inhibitors acting as host-targeting antiviral agents, thus opening an avenue for the treatment of multiple viral infections due to their broad antiviral effects and ability to effectively prevent drug resistance. Therefore, the antiviral effect of CypA has the potential to promote CypA inhibitors as host-targeting drugs to CypA-involved etiological agent infections and human diseases. Key points • CypA is involved in the replication and infection of several viruses, pathogenic bacteria, mycoplasma, and parasites. • CypA inhibitors are in a strong position to inhibit the infection of viruses, bacterial, and mycoplasma.

Objectives: The aim of this work is to evaluate the susceptibility profile of the isolates against antifungal drugs and the level of virulent genes and resistant genes mRNA expression of Candida nivariensis. Methods: We analyzed a collection of 9 C. nivariensis isolates from clinical isolates of Candida glabrata complex isolated from patients with vulvovaginal candidiasis (VVC). Antifungal susceptibilities of the isolates were assayed by using the broth microdilution method. The level of virulent genes and resistant genes mRNA expression was determined by using real-time PCR. Results: At day 7–14 and day 30–35 follow-up, mycological cure of VVC caused by C. nivariensis was 5 in 9 and 4 in 9 cases. The minimum inhibitory concentration geometric means of caspofungin, fluconazole, itraconazole, and amphotericin B in C. nivariensis isolates were higher than those in Candida albicans ATCC90028 (0.340, 1.852, 0.367, and 1.587 vs. 0.124, 0.140, 0.030, and 0.891 µg/mL; p < 0.05). The level of resistant genes ERG11, CDR1, and CDR2 and virulent genes YPS1, AWP3, and EPA1 mRNA expression was higher in C. nivariensis isolates than that of C. glabrata (2.58 ± 0.78, 9.31 ± 5.19, 11.10 ± 0.76, 13.57 ± 0.54, 11.96 ± 2.93, and 14.40 ± 0.61 vs. 1.05 ± 1.19, 2.22 ± 0.27, 0.85 ± 0.48, 0.30 ± 0.37, 1.90 ± 0.43, and 2.40 ± 0.65). Conclusion: We conclude that patients infected with C. nivariensis were symptomatic and with a low mycological cure rate when treated with commonly used antifungal agents. Compared with C. albicans, C. nivariensis is more antifungal resistant and virulent.

Publisher Copyright: IEEE Reconfigurable intelligent surface (RIS) is a new and revolutionary technology to achieve spectrum-, energy- and cost-efficient wireless networks. This paper studies the resource allocation for RIS-empowered device-to-device (D2D) communication underlaying a cellular network, in which an RIS is employed to enhance desired signals and suppress interference between paired D2D and cellular links. We maximize the overall network’s spectrum efficiency (SE) and energy efficiency (EE), respectively, by jointly optimizing the spectrum reuse indicators, the transmit power, the RIS’s passive beamforming and the BS’s receive beamforming. To solve both mixed-integer non-linear programming problems, we first propose an efficient and low-complexity user-pairing scheme based on relative channel strength to determine the spectrum reuse indicators. Other variables are then optimized to maximize the SE by an iterative algorithm, based on the techniques of alternating optimization, successive convex approximation,Lagrangian dual transform and quadratic transform. The EE-maximization problem is solved by an alternating algorithm integrated with Dinkelbach’s method. Numerical results show that the proposed design achieves significant SE and EE enhancements compared to traditional underlay D2D network without RIS, relay-assisted D2D network and other benchmarks.

Berberine is a quaternary isoquinoline alkaloid that possesses a significant therapeutic effect on a variety of cancers. However, due to poor bioavailability, an increased dose is often required to achieve therapeutic goals. To improve the activities of natural berberine, most modifications were focused on the positive isoquinoline unit by grafting long aliphatic chains or heterocycles. However, the negative part is ignored. At this point, the strategy of salt formation modifications with short- and medium-chain fatty acids was proposed in this article.Using salt modification to enhance the antitumor activity of berberine and explore the mechanism.Four short- and medium-chain fatty acid salts of berberine were prepared from berberine hydrochloride by salt formation modification with the sodium salt of butyric, caproic, octanoic, and decanoic acid, respectively. The cytotoxicity of four berberine salts on B16-F10, A549, HepG2, and U373 cancer cell lines was explored. Through cell localization, Mitochondrial membrane potential assay, and Western blotting analysis explored the mechanism of berberine salt-induced apoptosis. Its anticancer activity in vivo was demonstrated by the mouse xenograft model.The four berberine fatty acid salts exhibited an enhanced inhibitory effect on B16-F10, A549, HepG2, and U373 cancer cell lines, particularly on B16-F10 cells. Meanwhile, the four berberine fatty acid salts can inhibit the migration of B16-F10 cells. The four berberine fatty acid salts induce cancer cell apoptosis through the mitochondrial pathway, which was confirmed by the mitochondrial colocalization, the decreased mitochondrial membrane potential as well as activation of caspase-3, cytochrome C (Cyt-C), and down-regulated expression of B-cell lymphoma 2 (Bcl-2). Most importantly, the four berberine fatty acid salts inhibited tumor growth in the in vivo B16-F10 melanoma model without generating side effects intraperitoneally.This study revealed that salt formation modification may be an effective strategy to optimize the anticancer property of berberine hydrochloride and demonstrated the four berberine fatty acid salts induced apoptosis through the mitochondrial apoptotic pathway.

Mycoplasma genitalium, the smallest prokaryotic microorganism capable of independent replication, is increasingly recognized as a sexually transmitted pathogen. M. genitalium protein of adhesion (MgPa) plays a pivotal role in the process of M. genitalium adhesion to host cells. We previously identified cyclophilin A as a cellular receptor of MgPa using the virus overlay protein binding assay (VOPBA) together with liquid chromatography-mass spectrometry (LC-MS). In the current study, we have evaluated H2B as an alternative cellular receptor for MgPa since H2B was assigned the second higher score as a potential binding partner of MgPa in the VOPBA and LC-MS screen. It was found that recombinant MgPa specifically bind to H2B both in the SV-HUC-1 cell membrane and in form of a recombinant protein. H2B was detected throughout the SV-HUC-1 cells, including the cytoplasmic membrane, cytosol and nucleus. Importantly, H2B partially inhibited the adhesion of M. genitalium to SV-HUC-1 cells. Finally, H2B was both co-precipitated with recombinant MgPa and co-localized with M. genitalium and recombinant MgPa in SV-HUC-1 cells. The above observations suggest that H2B may act as a potential cellular receptor of MgPa for mediating M. genitalium adhesion to host cells.

Tuberculosis caused by Mycobacterium tuberculosis (M. tuberculosis) is the leading cause of death among infectious diseases in the worldwide. Lack of more sensitive and effective diagnostic reagents has increased the awareness of rapid diagnosis for tuberculosis. In this study, T7 phage displayed genomic DNA library of M. tuberculosis was constructed to screen the antigens that specially bind with TB-positive serum from the whole genome of M. tuberculosis and to improve the sensitivity and specificity of tuberculosis serological diagnosis. After three rounds of biopanning, results of DNA sequencing and BLAST analysis showed that 19 positive phages displayed four different proteins and the occurrence frequency of the phage which displayed ribokinase was the highest. The results of indirect ELISA and dot immunoblotting indicated that representative phages could specifically bind to tuberculosis-positive serum. The prokaryotic expression vector containing the DNA sequence of ribokinase gene was then constructed and the recombinant protein was expressed and purified to evaluate the serodiagnosis value of ribokinase. The reactivity of the recombinant ribokinase with different clinical serum was detected and the sensitivities and specificities in tuberculosis serodiagnosis were 90% and 86%, respectively by screening serum from tuberculosis patients (n = 90) and uninfected individuals (n = 90) based on ELISA. Therefore, this study demonstrated that ribokinase had good potential for the serodiagnosis of tuberculosis.

Funding Information: ACKNOWLEDGMENT This work of Gang Yang, Yating liao, and Ying-Chang Liang was supported by the National Natural Science Foundation of China (Grant No. 61631005, 62071093 and U1801261), the National Key Research and Development Program of China under Grant 2018YFB1801105 , the Fundamental Research Funds for the Central Universities under Grant ZYGX2019Z022, and the Programme of Introducing Talents of Discipline to Universities under Grant B20064. This work of Olav Tirkkonen was supported by Academy of Finland under Grant 319484. Publisher Copyright: ©2021 IEEE. Reconfigurable intelligent surfaces (RIS) are a new and revolutionary technology to achieve spectrum-, energy- and cost-efficient wireless networks. This paper studies the resource allocation for RIS-empowered device-to-device (D2D) communication underlaying a cellular network, in which an RIS is employed to enhance desired signals and suppress interference between paired D2D and cellular links. We maximize the sum rate of D2D users and cellular users by jointly optimizing the resource reuse indicators, the transmit power and the RIS’s passive beamforming. To solve the formulated non-convex problem, we first propose an efficient user-pairing scheme based on relative channel strength to determine the resource reuse indicators. Then, the transmit power and the RIS’s passive beamforming are jointly optimized by an iterative algorithm, based on the techniques of alternating optimization, successive convex approximation, Lagrangian dual transform and quadratic transform. Numerical results show that the proposed design outperforms the traditional D2D network without RIS.

The aim of this work is to evaluate the susceptibility profile of the isolates against antifungal drugs and the level of virulent genes and resistant genes mRNA expression of Candida nivariensis.We analyzed a collection of 9 C. nivariensis isolates from clinical isolates of Candida glabrata complex isolated from patients with vulvovaginal candidiasis (VVC). Antifungal susceptibilities of the isolates were assayed by using the broth microdilution method. The level of virulent genes and resistant genes mRNA expression was determined by using real-time PCR.At day 7-14 and day 30-35 follow-up, mycological cure of VVC caused by C. nivariensis was 5 in 9 and 4 in 9 cases. The minimum inhibitory concentration geometric means of caspofungin, fluconazole, itraconazole, and amphotericin B in C. nivariensis isolates were higher than those in Candida albicans ATCC90028 (0.340, 1.852, 0.367, and 1.587 vs. 0.124, 0.140, 0.030, and 0.891 µg/mL; p0.05). The level of resistant genes ERG11, CDR1, and CDR2 and virulent genes YPS1, AWP3, and EPA1 mRNA expression was higher in C. nivariensis isolates than that of C. glabrata (2.58 ± 0.78, 9.31 ± 5.19, 11.10 ± 0.76, 13.57 ± 0.54, 11.96 ± 2.93, and 14.40 ± 0.61 vs. 1.05 ± 1.19, 2.22 ± 0.27, 0.85 ± 0.48, 0.30 ± 0.37, 1.90 ± 0.43, and 2.40 ± 0.65).We conclude that patients infected with C. nivariensis were symptomatic and with a low mycological cure rate when treated with commonly used antifungal agents. Compared with C. albicans, C. nivariensis is more antifungal resistant and virulent.