The mitochondrial UPR induced by ATF5 attenuates intervertebral disc degeneration via cooperating with mitophagy.

Intervertebral disc degeneration (IVDD) is an aging disease that results in a low quality of life and heavy socioeconomic burden. The mitochondrial unfolded protein response (UPRmt) take part in various aging-related diseases. Our research intents to explore the role and underlying mechanism of UPRmt in IVDD. Nucleus pulposus (NP) cells were exposed to IL-1ß and nicotinamide riboside (NR) served as UPRmt inducer to treat NP cells. Detection of ATP, NAD + and NADH were used to determine the function of mitochondria. MRI, Safranin O-fast green and Immunohistochemical examination were used to determine the degree of IVDD in vivo. In this study, we discovered that UPRmt was increased markedly in the NP cells of human IVDD tissues than in healthy controls. In vitro, UPRmt and mitophagy levels were promoted in NP cells treated with IL-1ß. Upregulation of UPRmt by NR and Atf5 overexpression inhibited NP cell apoptosis and further improved mitophagy. Silencing of Pink1 reversed the protective effects of NR and inhibited mitophagy induced by the UPRmt. In vivo, NR might attenuate the degree of IDD by activating the UPRmt in rats. In summary, the UPRmt was involved in IVDD by regulating Pink1-induced mitophagy. Mitophagy induced by the UPRmt might be a latent treated target for IVDD.

Clinical and electroencephalogram characteristics of methylmalonic acidemia with MMACHC and MUT gene mutations.

OBJECTIVE: This study investigated the clinical, imaging, and electroencephalogram (EEG) characteristics of methylmalonic acidemia (MMA) with nervous system damage as the primary manifestation. METHODS: From January 2017 to November 2022, patients with nervous system injury as the main clinical manifestation, diagnosed with methylmalonic acidemia by metabolic and genetic testing, were enrolled and analyzed. Their clinical, imaging, and electroencephalogram data were analyzed. RESULTS: A total of 18 patients were enrolled, including 15 males and 3 females. The clinical symptoms were convulsions, poor feeding, growth retardation, disorder of consciousness, developmental delay, hypotonia, and blood system changes. There were 6 cases (33%) of hydrocephalus, 9 (50%) of extracerebral space widened, 5 (27%) of corpus callosum thinning, 3 (17%) of ventricular dilation, 3 (17%) of abnormal signals in the brain parenchyma (frontal lobe, basal ganglia region, and brain stem), and 3 (17%) of abnormal signals in the lateral paraventricular. In addition, there were 3 cases (17%) of cerebral white matter atrophy and 1 (5%) of cytotoxic edema in the basal ganglia and cerebral peduncle. EEG data displayed 2 cases (11%) of hypsarrhythmia, 3 (17%) of voltage reduction, 12(67%) of abnormal discharge, 13 (72%) of abnormal sleep physiological waves or abnormal sleep structure, 1 (5%) of immature (delayed) EEG development, and 8 (44%) of slow background. There were 2 cases (11%) of spasms, 1 (5%) of atonic seizures, and 1 (5%) of myoclonic seizures. There were 16 patients (89%) with hyperhomocysteinemia. During follow-up, 1 patient was lost to follow-up, and 1 died. In total, 87.5% (14/16) of the children had varying developmental delays. EEG was re-examined in 11 cases, of which 8 were normal, and 3 were abnormal. Treatments included intramuscular injections of vitamin B12, L-carnitine, betaine, folic acid, and oral antiepileptic therapy. Acute treatment included anti-infective, blood transfusion, fluid replacement, and correcting acidosis. The other treatments included low-protein diets and special formula milk powder. CONCLUSION: Methylmalonic acidemia can affect the central nervous system, leading to structural changes or abnormal signals on brain MRI. Metabolic screening and genetic testing help clarify the diagnosis. EEG can reflect changes in brain waves during the acute phase.

Soft tissue inflammation around upper third molar cause limited mouth opening: common but overlooked.

OBJECTIVES: The aim of this study was to explore inflammation of soft tissue around the upper third molar as a prevalent cause of limited mouth opening, identify the clinical and radiographic features, and summarize the therapeutic effectiveness of tooth extraction. MATERIALS AND METHODS: A retrospective analysis of data from 264 patients with limited mouth opening over the last five years was performed. RESULTS: Among the 264 patients, 24 (9.1%) had inflammation of the soft tissue around the upper third molar, which was the second most common cause of limited mouth opening. Twenty-one of the twenty-four affected patients, with an average mouth opening of 19.1 ± 7.6 mm, underwent upper third molar extraction. Gingival tenderness around the upper third molar or maxillary tuberosity mucosa was a characteristic clinical manifestation (p < 0.05). The characteristic features on maxillofacial CT included soft tissue swelling around the upper third molar and gap narrowing between the maxillary nodules and the mandibular ascending branch. Post extraction, the average mouth opening increased to 31.4 ± 4.9 mm (p < 0.05), and follow-up CT demonstrated regression of the inflammatory soft tissue around the upper third molar. CONCLUSIONS: Inflammation of soft tissue around the upper third molar is a common cause of limited mouth opening. Symptoms of pain associated with the upper third molar and distinctive findings on enhanced maxillofacial CT scans are crucial for diagnosis. Upper third molar extraction yields favorable therapeutic outcomes. CLINICAL RELEVANCE: Inflammation of the soft tissue around the maxillary third molar commonly causes limited mouth opening, but this phenomenon has long been overlooked. Clarifying this etiology can reduce the number of misdiagnosed patients with restricted mouth opening and enable more efficient treatment for patients.

3D-printed temporomandibular joint-mandible combined prosthesis: A prospective study.

OBJECTIVES: The study aimed to introduce and evaluate a new customized temporomandibular joint-mandible combined prosthesis with 3D printing fabrication. MATERIALS AND METHODS: This was a prospective study including patients with temporomandibular joint-mandible combined lesions. A 3D-printed customized temporomandibular joint-mandible combined prosthesis was implanted to repair the joint and jaw defect. Clinical follow-up and radiographic examinations were taken to assess the clinical efficacy. The assessment indices were compared by the Wilcoxon signed rank test. RESULTS: Eight patients were treated with the combined prosthesis and included in this study. All prostheses were accurately positioned and fixed without wound infection, prosthesis exposure, displacement, loosening, or fracture. All cases had no mass recurrence at the last follow-up point. Pain, diet, mandibular function, lateral mandibular movement to the diseased side, and maximal interincisal opening showed significant improvements at every follow-up point and went to a stable condition at 6 months after the operation. But the lateral movement to the non-operated side was still limited following surgery. CONCLUSION: The 3D-printed combined prosthesis may be an alternative to other well-established reconstructions for temporomandibular joint and mandible defects.

Safety and Efficacy of Polyetheretherketone (PEEK) Cages and Cadaveric Allografts in Transforaminal Lumbar Interbody Fusion (TLIF) for Treating Lumbar Pyogenic Spondylodiscitis.

Purpose: There have been many studies in the operative management of pyogenic spondylodiscitis with foreign materials. However, it still remains an issue of debate on whether the allografts may be used in pyogenic spondylodiscitis. This study sought to evaluate the safety and effectiveness of PEEK cages and the cadaveric allograft in transforaminal lumbar interbody fusion (TLIF) for treating lumbar pyogenic spondylodiscitis. Methods: From January 2012 to December 2019, 56 patients underwent surgery for lumbar pyogenic spondylodiscitis. The posterior debridement of all patients and their fusion with allografts, local bone grafts, and bone chip cages were performed before posterior pedicle screw fusion. An assessment of the residual pain, the grade of neurological injury, and the resolution of infection was conducted on 39 patients. The clinical outcome was evaluated using a visual analog scale (VAS) and the Oswestry Disability Index (ODI), and neurological outcomes were appraised based on Frankel grades. The radiological outcomes were evaluated via focal lordosis, lumbar lordosis, and the state of the fusion. Results: Staphylococcus aureus and Staphylococcus epidermidis were the most common causative organisms. The mean preoperative focal lordosis was -1.2° (-11.4° to 5.7°), and the mean postoperative focal lordosis increased to 10.3° (4.3°-17.2°). At the final follow-up, there were five cases with subsidence of the cage, no case of recurrence, and no case with cage and screw loosening or migration. The mean preoperative VAS and ODI scores were 8.9 and 74.6%, respectively, and improvements in VAS and ODI were 6.6 ± 2.2 and 50.4 ± 21.3%, respectively. The Frankel grade D was found in 10 patients and grade C in 7. Following the final follow-up, only one patient improved from Frankel grade C to grade D while the others recovered completely. Conclusion: The PEEK cage and cadaveric allograft combined with local bone grafts is a safe and effective choice for intervertebral fusion and restoring sagittal alignment without increased incidence of relapse for treating lumbar pyogenic spondylodiscitis.

The impact of the self-recognition ability and physical quality on coupled negative information-behavior-epidemic dynamics in multiplex networks.

In recent years, as the COVID-19 global pandemic evolves, many unprecedented new patterns of epidemic transmission continue to emerge. Reducing the impact of negative information diffusion, calling for individuals to adopt immunization behaviors, and decreasing the infection risk are of great importance to maintain public health and safety. In this paper, we construct a coupled negative information-behavior-epidemic dynamics model by considering the influence of the individual's self-recognition ability and physical quality in multiplex networks. We introduce the Heaviside step function to explore the effect of decision-adoption process on the transmission for each layer, and assume the heterogeneity of the self-recognition ability and physical quality obey the Gaussian distribution. Then, we use the microscopic Markov chain approach (MMCA) to describe the dynamic process and derive the epidemic threshold. Our findings suggest that increasing the clarification strength of mass media and enhancing individuals' self-recognition ability can facilitate the control of the epidemic. And, increasing physical quality can delay the epidemic outbreak and leads to suppress the scale of epidemic transmission. Moreover, the heterogeneity of the individuals in the information diffusion layer leads to a two-stage phase transition, while it leads to a continuous phase transition in the epidemic layer. Our results can provide favorable references for managers in controlling negative information, urging immunization behaviors and suppressing epidemics.

Introduction of temporomandibular joint and skull base combined reconstruction by autogenous bone graft.

OBJECTIVE: This study introduces the application of autogenous bone graft for the reconstruction of temporomandibular joint (TMJ) and skull base combined defects. MATERIALS AND METHODS: Patients treated with autogenous bone grafts for reconstruction of the TMJ and skull base were reviewed. All patients underwent virtual surgical design to confirm the osteotomies of the combined lesion and the selections of autogenous bone graft, fabrication of surgical templates to transfer the plan to actual operation, and reconstruction of autogenous bone graft for the TMJ and/or skull base. Surgical outcomes were assessed by clinical examinations and radiological data. RESULTS: Twenty-two patients were involved in this study. Ten patients underwent reconstruction of the skull base by a free iliac or temporal bone graft and preservation of the TMJ. Twelve patients underwent skull base reconstruction by the same methods and total reconstruction of the TMJ by half sternoclavicular joint flap or costochondral bone graft. No severe complications occurred after surgery. The occlusion relationship was stable and similar to that of the preoperative state. The pain and maximal interincisal opening were significantly improved by the 101.2-month follow-up. CONCLUSION: Autogenous bone graft is a good alternative for repairing the TMJ and the skull base structure and function. CLINICAL RELEVANCE: The study introduced the application of autogenous bone graft for the reconstruction of temporomandibular joint and skull base combined defect, which is a good way to repair the defect and restore the function.

Efficacy Evaluation of Temporomandibular Arthroscopic-Assisted Masseter Nerve Avulsion on Hemimasticatory Spasm.

PURPOSE: Hemimasticatory spasm (HMS) is a masticatory muscle disorder without an effective treatment approach at present. This retrospective analysis aims to investigate the clinical efficacy of temporomandibular arthroscope-assisted masseteric nerve avulsion on HMS and thereby further determine a more effective therapeutic strategy for HMS patients. METHODS: Four patients with HMS receiving temporomandibular arthroscope-assisted masseteric nerve avulsion in the neurology department of oral surgery of our hospital from April 2017 to April 2018 were recruited in this study. Through a clinical follow-up period of 36 months, the comprehensive efficacy of arthroscope-assisted masseteric nerve avulsion was evaluated combined with an electrophysiological electromyogram. Furthermore, the maximum muscle strength and masticatory efficiency of the sound and affected sides were measured to determine whether there were complications. The morphology of the myelin sheath of the masseteric nerve avulsed in the operation was observed under the transmission electron microscope. RESULTS: The 3 years of follow-up showed that complete remission of HMS was seen in 4 patients with the score reduced to grade 0, showing satisfactory clinical efficacy. Electrophysiological electromyogram demonstrated an absence of obvious high-frequency group discharge potential in the 4 patients within 3 years after the operation, and the overall efficacy combined with the clinical efficacy was considered satisfactory. The maximum masseter strength of the sound side had no significant change, but that of the affected side was slightly decreased. The masticatory efficiency of the affected side was slightly decreased immediately after the operation but returned to the preoperative level 1 year after the operation, suggesting that this operation did not affect the masticatory function of the patients. No obvious demyelination was found in the avulsed nervous tissues. CONCLUSIONS: Temporomandibular arthroscope-assisted masseteric nerve avulsion yielded satisfactory and stable overall efficacy on the treatment of HMS. The masticatory efficiency of the affected side was optimally preserved, while the maximum masseter muscle strength of the affected side was partially decreased.

Involvement of oxidative stress-induced annulus fibrosus cell and nucleus pulposus cell ferroptosis in intervertebral disc degeneration pathogenesis.

Ferroptosis is a necrotic form of regulated cell death that was associated with lipid peroxidation and free iron-mediated Fenton reactions. It has been reported that iron deficiency had been implicated in the pathogenesis of intervertebral disc degeneration (IVDD) by activating apoptosis. However, the role of ferroptosis in the process of IVDD has not been illuminated. Here, we demonstrate the involvement of ferroptosis in IVDD pathogenesis. Our in vitro models show the changes in protein levels of ferroptosis marker and enhanced lipid peroxidation level during oxidative stress. Safranin O staining, hematoxylin-eosin staining, and immunohistochemical were used to assess the IVDD after 8 weeks of surgical procedure in vivo. Treatment with ferrostatin-1, deferoxamine, and RSL3 demonstrate the role of ferroptosis in tert-butyl hydroperoxide (TBHP)-treated annulus fibrosus cells (AFCs) and nucleus pulposus cells (NPCs). Ferritinophagy, nuclear receptor coactivator 4 (NCOA4)-mediated ferritin selective autophagy, is originated during the process of ferroptosis in response to TBHP treatment. Knockdown and overexpression NCOA4 further prove TBHP may induce ferroptosis of AFCs and NPCs in an autophagy-dependent way. These findings support a role for oxidative stress-induced ferroptosis in the pathogenesis of IVDD.

Exosomes derived from vascular endothelial cells antagonize glucocorticoid-induced osteoporosis by inhibiting ferritinophagy with resultant limited ferroptosis of osteoblasts.

High dose and long-term steroid treatment can alter antioxidative ability and decrease the viability and function of osteoblasts, leading to osteoporosis and osteonecrosis. Ferroptosis, a new type of cell death characterized by excessive lipid peroxidation due to the downregulation of GPX4 and system Xc- , is involved in glucocorticoid-induced osteoporosis. Endothelial cell-secreted exosomes (EC-Exos) are important mediators of cell-to-cell communication and are involved in many physiological and pathological processes. However, the effect of EC-Exos on osteoblasts exposed to glucocorticoids has not been reported. Here, we explored the role of EC-Exos in glucocorticoid-induced osteoporosis. In vivo and in vitro experiments indicated that EC-Exos reversed the glucocorticoid-induced osteogenic inhibition of osteoblasts by inhibiting ferritinophagy-dependent ferroptosis.

Digital in-service relative time delay estimation for SDM self-homodyne coherent systems.

For space division multiplexing self-homodyne coherent systems, we propose a novel digital in-service relative time delay (RTD) estimation method without any additional optoelectronic device. Taking advantage of the frequency-domain periodicity of the colored frequency modulation noise, we manage to find the peak with location reflecting the RTD in its autocorrelation function (ACF). The peak to average ratio is further enhanced by leveraging a low-pass differential finite impulse response filter for robust identification. By simulations, the method is validated to be feasible for various linewidths, formats (16QAM, 32QAM and 64QAM), and links up to 80 km. Particularly, it is proved to be inherently compatible with large-linewidth low-cost lasers for the 10-km link. Also, for a low-complexity implementation, we discuss the way to reduce the number of points used to calculate the ACF while maintaining the same dynamic range. Furthermore, we demonstrate a 50-GBaud 16-QAM experiment to investigate its performances. With received optical power varying from -11 dBm to -17 dBm, 216 points are sufficient to provide an estimation accuracy of standard deviation (STD) less than 0.089 ns for the RTD range of [2.6, 491.0 ns]. The STD can be lowered to 0.036 ns by adopting 218 points. Especially, at -11-dBm ROP, the highest performance has been achieved with an accuracy smaller than the symbol period (0.018-ns STD) and a RTD range of [1.5, 491.0 ns].

Epigenetic regulation of virulence and the transcription of ribosomal protein genes involves a YEATS family protein in Cryptococcus deneoformans.

Epigenetic marks or post-translational modifications on histones have important regulatory roles in gene expression in eukaryotic organisms. The epigenetic regulation of gene expression in the pathogenic yeast Cryptococcus deneoformans remains largely undetermined. The YEATS domain proteins are readers of crotonylated lysine residues in histones. Here, we reported the identification of a single-copy gene putatively coding for a YEATS domain protein (Yst1) in C. deneoformans. To define its function, we created a mutant strain, yst1Δ, using CRISPR-Cas9 editing. yst1Δ exhibited defects in phenotype, for instance, it was hypersensitive to osmotic stress in the presence of 1.3 M NaCl or KCl. Furthermore, it was hypersensitive to 1% Congo red, suggesting defects in the cell wall. Interestingly, RNA-seq data revealed that Yst1p was critical for the expression of genes encoding the ribosomal proteins, that is, most were expressed with significantly lower levels of mRNA in yst1Δ than in the wild-type strain. The mutant strain was hypersensitive to low temperature and anti-ribosomal drugs, which we putatively attribute to the impairment in ribosomal function. In addition, the yst1Δ strain was less virulent to Galleria mellonella. These results generally suggest that Yst1, as a histone modification reader, might be a key coordinator of the transcriptome of this human pathogen. Yst1 could be a potential target for novel antifungal drugs, which might lead to significant developments in the clinical treatment of cryptococcosis.

miR-155 increases stemness and decitabine resistance in triple-negative breast cancer cells by inhibiting TSPAN5.

Effective therapeutic targets for triple-negative breast cancer (TNBC), a special type of breast cancer (BC) with rapid metastasis and poor prognosis, are lacking, especially for patients with chemotherapy resistance. Decitabine (DCA) is a Food and Drug Administration-approved DNA methyltransferase inhibitor that has been proven effective for the treatment of tumors. However, its antitumor effect in cancer cells is limited by multidrug resistance. Cancer stem cells (CSCs), which are thought to act as seeds during tumor formation, regulate tumorigenesis, metastasis, and drug resistance through complex signaling. Our previous study found that miR-155 is upregulated in BC, but whether and how miR-155 regulates DCA resistance is unclear. In this study, we demonstrated that miR-155 was upregulated in CD24- CD44+ BC stem cells (BCSCs). In addition, the overexpression of miR-155 increased the number of CD24- CD44+ CSCs, DCA resistance and tumor clone formation in MDA-231 and BT-549 BC cells, and knockdown of miR-155 inhibited DCA resistance and stemness in BCSCs in vitro. Moreover, miR-155 induced stemness and DCA resistance by inhibiting the direct target gene tetraspanin-5 (TSPAN5). We further confirmed that overexpression of TSPAN5 abrogated the effect of miR-155 in promoting stemness and DCA resistance in BC cells. Our data show that miR-155 increases stemness and DCA resistance in BC cells by targeting TSPAN5. These data provide a therapeutic strategy and mechanistic basis for future possible clinical applications targeting the miR-155/TSPAN5 signaling axis in the treatment of TNBC.

Rumor spreading in complex networks under stochastic node activity.

The research on rumor spreading has a long history, and its wanton flooding has brought huge impact on people's life. In the process of its spreading, the individual's activity plays an important role. However, in the complex and changeable environment, randomness cannot be ignored, not to mention its influence on individual activity Based on the I S R model of individual activity, this paper explores the stochastic version of the rumor model including fluctuations in the activity. Then, the influence of Stratonovich stochastic noise on the asymptotic behavior of non-linear rumor spreading model is studied. Through the mathematical analysis, we get the critical values to measure whether the deterministic and stochastics models spread or not, as well as the threshold conditions for rumor to spread wantonly. At the same time, the effects of Stratonovich stochastic noise on the asymptotic behavior of rumor-free equilibrium point E 0 and endemic equilibrium point E ∗ are obtained respectively, and the condition that the rumor-free equilibrium is globally asymptotically stable in the presence of noise is given. Finally, the theoretical results are verified by numerical simulation.

Long-period fiber gratings inscribed in few-mode fibers for discriminative determination.

We successfully fabricated the long-period fiber gratings in few-mode fibers (FMF-LPFGs) with micro-tapered method, which are different from the traditional LPFGs that only couple the fundamental mode to different cladding modes to obtain multiple resonant dips. There are two resonant dips on the transmission spectrum of the FMF-LPFGs, which are induced by the coupling between the fundamental mode and the low-order cladding mode LP03 (dip 1) and the coupling between the fundamental mode and the high-order core mode LP11 (dip 2). Due to the difference of the coupling mechanism involved in two dips, the shift of resonant wavelengths has different characteristics with the variation of the external environment parameter. The corresponding wavelength of dip 1 exhibits a red shift as the temperature increased. But for dip 2, the resonant wavelength has a blue shift. In addition, the two dips have different temperature and strain sensitivities. Therefore, discriminative determination of temperature and strain is realized by establishing the cross coefficient matrix, and the relative measurement error is less than 3%. What's more, we theoretically analyzed the reason why the two resonant wavelengths shift toward opposite direction with the increase of temperature and toward the same direction with the increase of strain.

Role of the fungus-specific flavin carrier Flc1 in antifungal resistance in the fungal pathogen Cryptococcus neoformans.

FLC family, a conserved fungus-specific family of integral membrane proteins, has been demonstrated to play important roles in flavin transport, growth, and virulence in several fungi but not yet in Cryptococcus neoformans. In this study, we have identified the single homologue of flavin adenine dinucleotide transporter in the opportunistic pathogen C. neoformans. The computational and phylogenetic analysis confirmed the fungal specificity of cryptococcal Flc1 protein, thus providing a promising drug target for clinical treatment of cryptococcosis. Disruption of FLC1 conferred sensitivity to 1% Congo red and 0.02% SDS, as well as leading to impaired chitin distribution in cell wall as observed with Calcofluor White staining, which collectively indicated the roles of FLC1 in maintenance of cell wall integrity. Further investigations revealed the defects of flc1Δ mutant in resistance to poor nutrition and elevated temperatures, and the ability to undergo invasive growth under nutrient-depleted conditions was reduced as well in flc1Δ mutant, suggesting the roles of Flc1 in response to environmental stresses. More importantly, our results showed that flc1Δ mutant exhibited severe susceptibility to antifungal aminoglycosides (hygromycin B and geneticin) and amphotericin B, but developed multidrug resistance to flucytosine and rapamycin, which provided great hints for therapeutic failure of cryptococcosis in clinic with the standard combination therapy. Finally, typical virulence factors including melanin biosynthesis and capsule formation in flc1Δ mutant were reduced as well, indicating the possible involvement of Flc1 in virulence.

Bidirectional long-reach PON using Kramers-Kronig-based receiver for Rayleigh Backscattering noise and SSBI interference elimination.

In this paper, a novel bidirectional long-reach PON is proposed and demonstrated by using Kramers-Kronig (KK)-based receiver and 7-core fiber to simultaneously cope with the induced signal-signal beating interference (SSBI) and Rayleigh backscattering (RB) noises. A low-cost self-homodyne detection using only one PD is used at both OLT and ONU, and the middle core of 7-core fiber is used to deliver the seed light to ONUs for colorless upstream transmission, and the upstream and downstream signals are transmitted simultaneously over the same outer core for each ONU. By this means, the signals and local oscillators for upstream and downstream transmission all originate from the same laser which is located at OLT. With the help of the KK-based receiver, SSBI could be effectively eliminated and the fiber dispersion can also be digitally compensated due to the reconstruction of the complex field of the received signal. Moreover, by using single sideband Nyquist-shaped subcarrier modulation with 16-ary quadrature amplitude modulation (SSB-Nyquist-16QAM) technique, the upstream and downstream signals are allocated to occupy the left and right sideband of the optical carrier respectively, and thus the RB noise can be easily removed by a simple optical filter in the receiver. In our experiment, the carrier-to-signal power ratio (CSPR) and the frequency gap between the upstream and downstream signals are investigated. Furthermore, bidirectional transmission of 60 Gbps SSB-Nyquist-16QAM signals over 50 km 7-core fiber are successfully achieved, and the frequency gap between the upstream and downstream signals is only 3 GHz.

Design of highly mode group selective photonic lanterns with geometric optimization.

Highly mode group selective photonic lanterns (PLs) are desired for mode-division multiplexing transmission systems. Usually, mode selectivity is achieved by using input fibers with different core diameters or refractive indices to break degeneracy between mode groups. We demonstrate that mode group selectivity can be greatly improved by optimizing core geometry of PLs. For three-mode PLs with optimized core geometry, based on beam propagation method (BPM) simulation results, mode selectivity is improved from 23.8 dB to 43.9 dB for LP01 mode, and mode selectivity of LP11 mode is improved from 26.8 dB to 45.5 dB. The reason is the optimized core geometry can significantly slow down the changing of mode profile along the taper of the PL; thus adiabatic tapering requirement can be greatly alleviated. It can also be observed that the simulation results by the BPM are in good agreement with calculation of coupled-mode theory.

Identification of a basidiomycete-specific Vilse-like GTPase activating proteins (GAPs) and its roles in the production of virulence factors in Cryptococcus neoformans.

Cryptococcus neoformans is a basidiomycetous pathogenic yeast that causes fatal infections in both immunocompetent and immunocompromised patients. Regulation on the production of its virulence factors is not fully understood. Here we reported the characterization of a gene, named CVH1(CNA06260), encoding a Drosophila Vilse-like RhoGAP homolog, which is hallmarked by three conserved functional domains: WW, MyTH4 and RhoGAP. Phylogenetic analysis suggests that CVH1 is highly conserved from protists to mammals and interestingly in basidiomycetes, but absent in plants or Ascomycota and other lower fungi. This phylogenetic distribution indicates an evolutionary link among these groups of organisms. Functional analyses demonstrated that CVH1 was involved in stress tolerance and virulence factor production. By disrupting CVH1, we created a second mutant cvh1Δ with the CRISPR-Cas9 editing tool. The mutant strain exhibited hypersensitivity to osmotic stress by 2 M sorbitol and NaCl, suggesting defects in the HOG signaling pathway and an interaction of Cvh1 with the HOG pathway. Hypersensitivity of cvh1Δ to 1% Congo red and 0.01% SDS suggests that the cell wall integrity was impaired in the mutant. And cvh1Δ hardly produced the pigment melanin and capsule. Our study for the first time demonstrates that the fungal Vilse-like RhoGAP CVH1 is an important regulator of multiple biological processes in C. neoformans, and provides novel insights into the regulatory circuit of stress resistance/cell wall integrity, and laccase and capsule synthesis in C. neoformans.

Bacterial Contribution in Chronicity of Wounds.

A wound is damage of a tissue usually caused by laceration of a membrane, generally the skin. Wound healing is accomplished in three stages in healthy individuals, including inflammatory, proliferative, and remodeling stages. Healing of wounds normally starts from the inflammatory phase and ends up in the remodeling phase, but chronic wounds remain in an inflammatory stage and do not show progression due to some specific reasons. Chronic wounds are classified in different categories, such as diabetic foot ulcer (DFU), venous leg ulcers (VLU) and pressure ulcer (PU), surgical site infection (SSI), abscess, or trauma ulcers. Globally, the incidence rate of DFU is 1-4 % and prevalence rate is 5.3-10.5 %. However, colonization of pathogenic bacteria at the wound site is associated with wound chronicity. Most chronic wounds contain more than one bacterial species and produce a synergetic effect that results in previously non-virulent bacterial species becoming virulent and causing damage to the host. While investigating bacterial diversity in chronic wounds, Staphylococcus, Pseudomonas, Peptoniphilus, Enterobacter, Stenotrophomonas, Finegoldia, and Serratia were found most frequently in chronic wounds. Recently, it has been observed that bacteria in chronic wounds develop biofilms that contribute to a delay in healing. In a mature biofilm, bacteria grow slowly due to deficiency of nutrients that results in the resistance of bacteria to antibiotics. The present review reflects the reasons why acute wounds become chronic. Interesting findings include the bacterial load, which forms biofilms and shows high-level resistance toward antibiotics, which is a threat to human health in general and particularly to some patients who have acute wounds.